A Multicenter, Open-label (Part A) Followed by a Randomized, Double-blind, Parallel-group, Placebo Controlled Study (Part B) to Evaluate Maintenance of Remission in Subjects With Active Axial Spondyloarthritis (axSpA) Receiving Either Certolizumab Pegol 200 mg Q2W or 200 mg Q4W as Compared to Placebo
Phase: PHASE3
Conditions: Axial Spondyloarthrithis, Ankylosing Spondylitis
Sponsor: UCB BIOSCIENCES GmbH

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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 1 of 173
PROTOCOL AS0005 AMENDMENT 2
MULTICENTER, OPEN-LABEL (PART A) FOLLOWED BY A 
RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, 
PLACEBO-CONTROLLED STUDY (PART B) TO EVALUATE 
MAINTENANCE OF REMISSION IN SUBJECTS WITH ACTIVE 
AXIAL SPONDYLOARTHRITIS (AXSPA) RECEIVING EITHER 
CERTOLIZUMAB PEGOL 200MG Q2W OR 200MG Q4W AS 
COMPARED TO PLACEBO
PHASE 3B
EudraCT Number: 2015-000339-34
IND Number: 9,869
Sponsor:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Protocol/Amendment number
Date
Type of 
amendment
Final Protocol
27 Mar 2015
Not applicable
Protocol Amendment 0.1 (Taiwan)
24 Jun 2015
Substantial
Protocol Amendment 0.2 (United 
Kingdom)
31 Jul 2015
Substantial
Protocol Amendment 1
24 Nov 2015
Substantial
Protocol Amendment 1.1 (Taiwan)
18 Dec 2015
Substantial
Protocol Amendment 1.2 
(United Kingdom)
18 Dec 2015
Substantial
Protocol Amendment 2
24 Jan 2018
Non-substantial
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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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 2 of 173
STUDY CONTACT INFORMATION
Sponsor
UCB BIOSCIENCES GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
GERMANY
Sponsor Study Physician
Name:
Address:
Alfred-Nobel-Strasse 10
40789 Monheim, Germany
Phone:
Fax:
Clinical Project Manager
Name:
Address:
Alfred-Nobel-Strasse 10
40789 Monheim, Germany
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 3 of 173
Clinical Monitoring Contract Research Organization
Name:
PAREXEL International GmbH
Address:
Klinikum Westend, Haus 18
Spandauer Damm 130
14050 Berlin
Germany
Phone:
+49 30 30 685 0
Fax:
+49 30 30 685 299
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 4 of 173
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 24 21
USA: +1 800 880 6949
or +1 866 890 3175
Canada: +1 877 582 8842
Email
Global: DS_ICT@ucb.com (for interventional clinical studies)
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 5 of 173
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................16
2
INTRODUCTION ...........................................................................................................17
2.1
Natural history of axial spondyloarthritis ..............................................................17
2.2
Burden of disease in axial spondyloarthritis..........................................................19
2.3
Diagnosing axial spondyloarthritis in clinical practice..........................................19
2.4
Current management of axial spondyloarthritis.....................................................20
2.5
Rationale ................................................................................................................21
3
STUDY OBJECTIVES....................................................................................................22
3.1
Primary objective...................................................................................................22
3.2
Secondary objectives .............................................................................................22
3.3
Other objectives .....................................................................................................22
3.4
Pharmacokinetic, pharmacogenomic, and immunological objectives...................23
4
STUDY VARIABLES.....................................................................................................23
4.1
Efficacy variable....................................................................................................23
4.1.1
Primary efficacy variable.............................................................................23
4.1.2
Secondary efficacy variables .......................................................................23
4.1.2.1
Secondary efficacy variables for subjects entering Part A ................23
4.1.2.2
Secondary efficacy variables for subjects entering Part B.................23
4.1.2.3
Secondary efficacy variables for subjects who experience a flare in 
Part B .................................................................................................24
4.1.3
Other efficacy variables...............................................................................24
4.1.3.1
Other efficacy variables for subjects entering Part A ........................24
4.1.3.2
Other efficacy variables for subjects entering Part B ........................25
4.1.3.3
Other efficacy variables for subjects who experience a flare in Part B26
4.2
Pharmacokinetic and pharmacogenomic variables................................................28
4.2.1
Pharmacokinetic variables...........................................................................28
4.2.2
Biomarkers...................................................................................................28
4.2.3
Pharmacogenomic variables ........................................................................28
4.3
Immunogenicity variables......................................................................................28
4.4
Safety variables......................................................................................................28
5
STUDY DESIGN.............................................................................................................29
5.1
Study description ...................................................................................................29
5.1.1
Part A...........................................................................................................29
5.1.2
Part B ...........................................................................................................30
5.1.3
Escape treatment..........................................................................................31
5.1.4
Study duration per subject ...........................................................................31
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Clinical Study Protocol
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AS0005
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5.1.5
Planned number of subjects and sites ..........................................................31
5.1.6
Anticipated regions and countries................................................................31
5.2
Schedule of study assessments...............................................................................31
5.3
Schematic diagram.................................................................................................39
5.4
Rationale for study design and selection of dose...................................................39
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................40
6.1
Inclusion criteria ....................................................................................................40
6.2
Exclusion criteria ...................................................................................................41
6.3
Withdrawal and escape criteria..............................................................................47
6.3.1
Withdrawal criteria ......................................................................................47
6.3.2
Escape treatment..........................................................................................47
7
STUDY TREATMENT(S) ..............................................................................................48
7.1
Description of investigational medicinal product(s)..............................................48
7.2
Treatment(s) to be administered ............................................................................48
7.2.1
Treatment administration.............................................................................48
7.3
Packaging...............................................................................................................49
7.4
Labeling .................................................................................................................49
7.5
Handling and storage requirements .......................................................................49
7.6
Drug accountability................................................................................................50
7.7
Procedures for monitoring subject compliance......................................................50
7.8
Concomitant medication(s)/treatment(s) ...............................................................51
7.8.1
Permitted concomitant treatments (medications and therapies) ..................51
7.8.2
Prohibited concomitant treatments (medications and therapies) .................52
7.8.3
Rescue medication.......................................................................................52
7.9
Blinding..................................................................................................................52
7.9.1
Procedures for maintaining and breaking the treatment blind.....................54
7.9.1.1
Maintenance of study treatment blind................................................54
7.9.1.2
Breaking the treatment blind in an emergency situation....................54
7.10
Randomization and numbering of subjects............................................................55
8
STUDY PROCEDURES BY VISIT ...............................................................................56
8.1
Screening Visit (up to 5 weeks).............................................................................56
8.2
Baseline Visit (Week 0).........................................................................................57
8.3
Weeks 2 to 96/WD onsite visits.............................................................................58
8.3.1
Weeks 2, 4, 12, 24, 32, 36, 48, 52, 60, 72, 84, and 96/WD (± 3 Days).......58
8.3.2
3 to 5 days prior to Week 48........................................................................60
8.4
Weeks 6 to 94 home visits and home nurse visits .................................................60
8.4.1
Home visits during Part A ...........................................................................60
8.4.2
Home and home nurse visits during Part B .................................................60
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AS0005
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8.5
Study procedures after flare until the final assessment visit at Week 96/WD.......61
8.6
Safety Follow-Up Visit..........................................................................................63
8.7
Withdrawal Visit....................................................................................................63
8.8
Unscheduled Visit..................................................................................................63
9
ASSESSMENT OF EFFICACY......................................................................................63
9.1
Assessment of primary and secondary efficacy variables .....................................63
9.1.1
ASAS20, ASAS40, ASAS 5/6 response, and ASAS partial remission.......63
9.1.2
Bath ankylosing spondylitis disease activity index (BASDAI)...................64
9.1.3
Bath ankylosing spondylitis functional index (BASFI)...............................65
9.1.4
MRI assessments..........................................................................................65
9.1.5
Bath ankylosing spondylitis metrology index .............................................65
9.1.6
Total and nocturnal spinal pain NRS...........................................................66
9.1.7
Ankylosing spondylitis disease activity score (ASDAS) ............................66
9.2
Assessment of other efficacy variables..................................................................66
9.2.1
Ankylosing spondylitis quality of life .........................................................66
9.2.2
Work Productivity Survey ...........................................................................67
9.2.3
Patient’s global assessment of disease activity (NRS) ................................67
9.2.4
SF-36............................................................................................................67
9.2.5
Enthesitis (MASES).....................................................................................68
9.2.6
Swollen and tender joint counts (44 joints evaluation)................................68
9.2.7
Physician’s global assessment of disease activity .......................................69
9.2.8
Spinal mobility.............................................................................................69
9.2.9
Health status (EQ-5D) .................................................................................69
9.2.10
Resource utilization .....................................................................................69
9.2.11
Extra-articular assessments..........................................................................70
9.2.12
Fecal and serum calprotectin .......................................................................70
9.2.13
Inflammatory Bowel Disease Questionnaire assessment ............................70
10
ASSESSMENT OF PHARMACOKINETICS AND PHARMACOGENOMICS 
VARIABLE(S) ................................................................................................................71
11
ASSESSMENT OF IMMUNOGENICITY VARIABLES .............................................71
12
ASSESSMENT OF SAFETY..........................................................................................71
12.1
Adverse events.......................................................................................................71
12.1.1
Definition of adverse event..........................................................................71
12.1.2
Procedures for reporting and recording adverse events...............................72
12.1.3
Description of adverse events......................................................................72
12.1.4
Follow up of adverse events ........................................................................72
12.1.5
Rule for repetition of an adverse event........................................................73
12.1.6
Pregnancy.....................................................................................................73
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12.1.7
Overdose of investigational medicinal product ...........................................74
12.1.8
Safety signal detection.................................................................................74
12.2
Serious adverse events...........................................................................................74
12.2.1
Definition of serious adverse event .............................................................74
12.2.2
Procedures for reporting serious adverse events..........................................75
12.2.3
Follow up of serious adverse events............................................................76
12.3
Adverse events of interest......................................................................................76
12.4
Immediate reporting of adverse events..................................................................76
12.5
Anticipated serious adverse events........................................................................76
12.6
Laboratory measurements......................................................................................77
12.7
Other safety measurements....................................................................................78
12.7.1
Pregnancy testing.........................................................................................78
12.7.2
Physical assessments....................................................................................78
12.7.3
Assessment and management of TB and TB risk factors............................79
12.7.3.1
Tuberculosis assessments...................................................................81
12.7.3.2
Chest x-ray.........................................................................................81
12.7.3.3
Tuberculosis questionnaire ................................................................81
12.7.3.4
Tuberculosis management .................................................................81
12.7.4
Vital signs ....................................................................................................82
13
STUDY MANAGEMENT AND ADMINISTRATION.................................................83
13.1
Adherence to protocol............................................................................................83
13.2
Monitoring .............................................................................................................83
13.2.1
Definition of source data..............................................................................83
13.2.2
Source data verification ...............................................................................84
13.3
Data handling.........................................................................................................84
13.3.1
Case report form completion .......................................................................84
13.3.2
Electronic reporting outcome.......................................................................84
13.3.3
Database entry and reconciliation................................................................85
13.3.4
Subject screening and enrollment log/subject identification code list.........85
13.4
Termination of the study........................................................................................85
13.5
Archiving and data retention..................................................................................86
13.6
Audit and inspection ..............................................................................................86
13.7
Good clinical practice ............................................................................................86
14
STATISTICS ...................................................................................................................87
14.1
Definition of analysis sets......................................................................................87
14.2
General statistical considerations...........................................................................87
14.3
Planned efficacy analyses ......................................................................................88
14.3.1
Analysis of the primary efficacy variable....................................................88
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14.3.2
Analysis of the secondary efficacy variables...............................................88
14.3.2.1
Part A analysis ...................................................................................88
14.3.2.2
Part B analysis....................................................................................89
14.3.2.3
Part B analysis for subjects who experience a flare...........................90
14.3.3
Other efficacy analyses................................................................................91
14.3.3.1
Part A .................................................................................................91
14.3.3.2
Part B .................................................................................................91
14.3.3.3
Part B analysis for subjects who experience a flare...........................91
14.4
Planned safety and other analyses..........................................................................92
14.4.1
Safety analyses.............................................................................................92
14.4.2
Pharmacokinetic and immunogenicity analysis...........................................92
14.5
Handling of protocol deviations.............................................................................92
14.6
Handling of dropouts or missing data....................................................................92
14.7
Planned interim analysis and data monitoring.......................................................93
14.8
Determination of sample size.................................................................................93
15
ETHICS AND REGULATORY REQUIREMENTS......................................................94
15.1
Informed consent ...................................................................................................94
15.2
Subject identification cards....................................................................................94
15.3
Institutional review boards and independent ethics committees............................94
15.4
Subject privacy.......................................................................................................95
15.5
Protocol amendments.............................................................................................95
16
FINANCE, INSURANCE, AND PUBLICATION.........................................................96
17
REFERENCES ................................................................................................................97
18
APPENDICES ...............................................................................................................103
18.1
ASAS classification criteria for axSpA ...............................................................103
18.2
Corticosteroid equivalent doses...........................................................................104
18.3
Protocol Amendment 1 ........................................................................................105
18.4
Protocol Amendment 2 ........................................................................................148
19
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................172
20
SPONSOR DECLARATION ........................................................................................173
LIST OF TABLES
Table 5.1: Schedule of study assessments for all subjects completing Part A and Part B.....32
Table 5.2: Schedule of study assessments for all subjects experiencing a flare in Part B.....37
Table 6.1: Concomitant Medications (Prior to Baseline and Study Visits)...........................42
Table 9.1: Swelling and tenderness grading ..........................................................................69
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24 Jan 2018
Clinical Study Protocol
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AS0005
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Table 12.1: Anticipated serious adverse events in population independent of drug 
exposure................................................................................................................77
Table 12.2: Laboratory measurements.....................................................................................78
Table 18.1: Corticosteroid equivalent doses (with reference to prednisone 10mg dose)a ....104
LIST OF FIGURES
Figure 2.1: ASAS Classification criteria for axSpA ...............................................................20
Figure 5.1: Schematic diagram................................................................................................39
Figure 7.1: Injection Schedule ................................................................................................53
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24 Jan 2018
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LIST OF ABBREVIATIONS
AB
antibody
ABA
abatacept
ADA
adalimumab
ADAb
anti-CZP antibody
AE 
adverse event
AESI
adverse event of special interest
ANCOVA
analysis of covariance
AS
ankylosing spondylitis
ASAS
Assessment of SpondyloArthritis International Society 
ASAS20, 40
Assessment of SpondyloArthritis International Society 20%, 40% response 
criteria
ASAS5/6
ASAS 5 out of 6 response criteria
ASDAS
Ankylosing Spondylitis Disease Activity Score
ASDAS-CII
Ankylosing Spondylitis Disease Activity Score – Clinically Important 
Improvement
ASDAS-HD
Ankylosing Spondylitis Disease Activity Score – High Disease activity
ASDAS-ID
Ankylosing Spondylitis Disease Activity Score – Inactive Disease
ASDS-MD
Ankylosing Spondylitis Disease Activity Score – Moderate Disease
ASDAS-MI
Ankylosing Spondylitis Disease Activity Score – Major Improvement
ASDAS-vHD
Ankylosing Spondylitis Disease Activity Score – very High Disease activity
ASQoL
Ankylosing Spondylitis Quality of Life
ASspIMRI-a
Ankylosing Spondylitis spine MRI score for activity
axSpA
axial spondyloarthritis 
AZA
azathioprine
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
BASMI
Bath Ankylosing Spondylitis Metrology Index
BMO
bone marrow oedema
BMP
bone morphogenic protein 
CD
Crohn’s disease
CDMS
clinical data monitoring system
CI
confidence interval
COX-2
cyclooxygenase 2
CPM
Clinical Project Manager
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
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Page 12 of 173
CPMP
Committee for Proprietary Medicinal Products
CRF
Case Report Form
CRO
Contract Research Organization
CRP
C-reactive protein
CZP
certolizumab pegol
DKK1
Dickkopf-related protein 1
DMARD
disease-modifying antirheumatic drug
ECG
electrocardiogram
eCRF
electronic Case Report Form
ePRO
electronic patient reported outcome
EQ-5D
EuroQoL Health Status Questionnaire 5 dimensions
ES
Enrolled Set
ETN
etanercept
EULAR
European League Against Rheumatism
FAS
Full Analysis Set
FDS
Full Dose Set
FS
Flared Set
GCP
Good Clinical Practice
GM-CSF
Granulocyte macrophage colony-stimulating factor
GOL
golimumab
HCQ
hydroxychloroquine
HIV
human immunodeficiency virus
HLA-B27
human leukocyte antigen B27 
HRQoL
health-related quality of life
ia
intra-articular
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
IBD-Q
inflammatory bowel disease questionnaire
IBP
inflammatory back pain
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IFX
infliximab
IGRA
interferon-gamma release assay
IMP
investigational medicinal product
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IP
interphalangeal
IRB
Institutional Review Board
iv
intravenous
IXRS
interactive voice or web response system (IVRS or IWRS)
LFN
leflunomide
LOCF
last observation carried forward
LTB
latent tuberculosis
M-CSF
macrophage colony-stimulating factors
MASES
Maastricht Ankylosis Spondylitis Enthesitis Score
MCID
minimal clinically important difference
MCS
Mental Component Summary
MMP-3
matrix metalloproteinase-3
MMRM
mixed model for repeated measures
mNY
modified New York 
MRI
magnetic resonance imaging
MTX
methotrexate
NAb
neutralizing antibody
nr-axSpA
nonradiographic axSpA
NRI
nonresponse imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
NTMB
nontuberculosis mycobacterium
NYHA
New York Heart Association
OLS
Open-Label Set
OMERACT
Outcome Measures in Rheumatology Clinical Trials
PCS
Physical Component Summary
PEG
polyethylene glycol
PFS
prefilled syringe
PhGADA
Physician’s Global Assessment of Disease Activity
PtGADA
Patient’s Global Assessment of Disease Activity
PK
pharmacokinetics
PKSA
Pharmacokinetic Set A
PKSB
Pharmacokinetic Set B
PPS
Per Protocol Set
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24 Jan 2018
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PR
partial remission
prn
pro re nata (as needed)
PS
Patient Safety
PsA
psoriatic arthritis 
Q2W
every 2 weeks (every other week)
Q4W
every 4 weeks
QoL
quality of life
RA 
rheumatoid arthritis
RDC
remote data capture
RS
Randomized Set
SAARD
slow-acting anti-rheumatic drugs
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous(ly)
sCSF1r
soluble CSF-1 Receptor
SD
standard deviation
SF-36
Short-Form 36-Item Health Survey
SFU
Safety Follow-Up
SI
sacroiliac
SIJ
sacroiliac joint
SmPC
Summary of Product Characteristics
SOP
standard operating procedure
SpA
spondyloarthritis
SPARCC
Spondyloarthritis Research Consortium of Canada
SS
Safety Set
SSB
Safety Set Part B
SSCM
Single Safety Case Management
SSZ
sulfasalazine
STIR
short-tau-inversion recovery
TB
tuberculosis
TGF
Transforming Growth Factor
TNF
tumor necrosis factor
TNFα
tumor necrosis factor alpha
ULN
upper limit of normal
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VAS
visual analog scale
VEGF
vascular endothelial growth factor
WBC
white blood cell
WD
Withdrawal 
WHO
World Health Organization
WISP
Inducible Signaling Pathway proteins
WNT-1
wingless-related mouse mammary tumor virus integration site protein
WPS
Work Productivity Survey
REDACTED COPY 
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24 Jan 2018
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1
SUMMARY
Study AS0005 is a multicenter, open-label (Part A) followed by a randomized, double-blind, 
parallel-group, placebo-controlled clinical study (Part B) to evaluate the efficacy, safety, 
pharmacokinetics (PK), and immunogenicity of certolizumab pegol (CZP) in adult subjects with 
active axial spondyloarthritis (axSpA) in sustained remission who continued either on full-dose 
treatment (CZP 200mg every 2 weeks [Q2W]), on a dose reduction (CZP 200mg every 4 weeks 
[Q4W]) or withdrawal of CZP treatment (placebo). The study includes an Open-Label Run-In 
Period of 48 weeks (Part A) followed by a Double-Blind Period of 48 weeks (Part B) with 
3 treatment arms (200mg CZP Q2W [referred to as full-dose], 200mg CZP Q4W [referred to as 
half-dose], and placebo), and a Safety Follow-Up (SFU) Period for 10 weeks after the last dose 
of study medication.
Part A consists of 2 periods: Period 1 (Screening Period), 1 to 5 weeks before Baseline and 
Period 2 (Open-Label Period), Week 0 (Baseline) to Week 48. Eligible subjects will receive 
3 loading doses of CZP 400mg subcutaneous (sc) at Weeks 0 (Baseline), 2, and 4 followed by 
CZP 200mg Q2W in Period 2 from Week 6 to Week 46. All subjects who have not achieved 
sustained remission at the end of Period 2 will be discontinued from the study and treated at the 
discretion of their physician.
Part B consists of 2 periods: Period 3 (Double-Blind Period): Week 48 to Week 96, 
placebo-controlled and Period 4 (SFU Period): 10 weeks after the last dose of study medication. 
Subjects in sustained remission at the end of Part A will be randomized in a 1:1:1 ratio to the 
following treatment arms: 1) CZP administered sc at a dose of 200mg Q2W (full-dose), 2) CZP 
administered sc at a dose of 200mg Q4W (half-dose), and 3) placebo. All subjects, including 
those withdrawn from study treatment, will have an SFU Visit, 10 weeks after their last dose of 
study medication. Subjects experiencing a flare after randomization will be further treated with 
CZP 200mg Q2W (full-dose) until Week 96 or for at least 12 weeks after the flare, whatever 
period is longer (refer to Figure 7.1). 
The primary objective of the study is to evaluate the percentage of subjects who do not 
experience a flare on CZP 200mg Q2W (full-dose) or 200mg Q4W (half-dose) during Part B. 
The secondary objectives are as follows: 1) to evaluate the percentage of subjects achieving 
sustained remission at the end of Part A, 2) to evaluate the time to flare and other measures of 
signs and symptoms, to compare the percentage of subjects who do not experience a flare 
between CZP full-dose and half-dose, and to evaluate the efficacy of re-initiation of treatment 
with the CZP full-dose in subjects who experience a flare following a withdrawal or dose 
reduction of CZP for subjects randomized into Part B, 3) to assess safety and tolerability of CZP, 
and 4) to evaluate inflammatory changes over time as assessed by magnetic resonance imaging 
(MRI).
The other objectives as well as pharmacokinetic, pharmacogenomic, and immunological 
objectives are presented in Sections 3.3 and 3.4.
The primary efficacy variable is the percentage of subjects in Part B who do not experience a 
flare (refer to Section 3 for definition of flare). Secondary efficacy variables for subjects entering 
Part A are: 1) percentage of subjects achieving sustained remission at Week 48 and 
2) Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity and clinical 
improvement at Week 48.
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Clinical Study Protocol
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The following are secondary efficacy variables for subjects entering Part B: 1) time to flare, 
2) ASDAS disease activity and clinical improvement at Week 96, 3) assessment in Axial 
SpondyloArthritis International Society (ASAS) response criteria (ASAS20, ASAS40, ASAS 5 
out of 6 [ASAS 5/6], and ASAS partial remission [PR] responses) at Week 96, 4) change from 
Baseline in ASDAS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath 
Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Metrology 
Index (BASMI) at Week 96, 5) BASDAI50 response at Week 96, and 6) change from Baseline 
in Sacroiliac SpondyloArthritis Research Consortium of Canada (SPARCC) and ankylosing 
spondylitis spine MRI score for activity (ASspIMRI-a) in the Berlin modification scores at Week 
96.
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated at Escape Week 12: 1) ASDAS disease activity and clinical 
improvement, 2) ASAS20, ASAS40, ASAS5/6, and ASAS PR response, 3) change from 
Baseline in ASDAS, BASDAI, BASFI, BASMI, and 4) change from Baseline in sacroiliac 
SPARCC and ASspIMRI-a in the Berlin modification scores.
Further, other efficacy variables for Part A, Part B and for subjects who experience a flare in 
Part B are listed in Section 4.1.3.1, Section 4.1.3.2, and Section 4.1.3.3, respectively.
Pharmacokinetic and pharmacogenomic variables are listed in Section 4.2, and immunological 
variables are listed in Section 4.3.
Safety variables to be assessed are adverse events (AEs), physical examination, blood pressure, 
chest x-ray, and measurements of laboratory parameters (hematology, biochemistry, and 
urinalysis). At Screening, Week 48, and Week 96, all subjects will have an interferon-gamma 
release assay (IGRA) test (QuantiFERON TB GOLD In Tube test or another World Health 
Organization (WHO)-validated IGRA test such as Elispot, if QuantiFERON TB GOLD In Tube 
test is not available locally). Screening chest x-ray must have occurred within 3 months prior to 
Screening Visit and should be repeated only if the tuberculosis (TB) test was confirmed positive 
or any further evidence is suggestive of potential TB infection. In addition to a physical 
examination done intermittently throughout the study, subjects will be evaluated at Screening, 
Baseline, and every 12 weeks thereafter, including the Week 96/Withdrawal (WD) Visit, for 
signs and symptoms of latent or active TB infection and risk factors for exposure to TB using the 
TB questionnaire. 
Additionally it is planned to evaluate whether the response of axSpA-associated gut 
inflammation to CZP correlates with the response of the axSpA signs and symptoms. Correlation 
of fecal and serum calprotectin level with Inflammatory Bowel Disease Questionnaire (IBD-Q) 
and C-reactive protein (CRP) level will be evaluated in an exploratory manner.
2
INTRODUCTION
2.1
Natural history of axial spondyloarthritis
Spondyloarthritis (SpA) is an umbrella term applied to a family of rheumatic diseases that have 
both features in common with, as well as being distinct from, other inflammatory arthritides, 
particularly rheumatoid arthritis (RA).
Recently, the ASAS working group established classification criteria to distinguish 2 broad 
categories of SpA: peripheral SpA and axSpA (Rudwaleit, 2011; Rudwaleit, 2010; Rudwaleit, 
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Clinical Study Protocol
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Page 18 of 173
2009c). This division is based on the body part predominantly involved in the inflammatory 
process and those areas of the body that may respond similarly well to medication. Therefore, 
peripheral SpA includes diseases affecting mainly peripheral joints, such as reactive arthritis and 
psoriatic arthritis (PsA), whereas axSpA comprises those diseases with mainly axial involvement 
(sacroiliac joints and spine), including ankylosing spondylitis (AS) and nonradiographic axSpA 
(nr-axSpA).
Patients with AS have definitive evidence of structural changes in the sacroiliac joint 
(sacroiliitis) on x-ray, fulfilling the Modified New York classification criteria (mNY-positive) 
(van der Linden, 1984), whereas in those with nr-axSpA structural changes on conventional 
radiographs do not meet the mNY criteria (mNY-negative) (Rudwaleit, 2005; Dougados, 1991).
Axial SpA is a chronic inflammatory disease that impacts a substantial proportion of the 
population. Limited evidence exists regarding the exact prevalence of axSpA. In the US, 
however, recent data suggest that the prevalence is similar to that of RA (axSpA: 0.7% to 1.4%; 
RA: 0.5% to 1.0%) (Reveille; 2012; Myasoedova, 2010; Helmick, 2008) and a cross sectional 
cohort study conducted in a UK primary care population to investigate the prevalence of 
inflammatory back pain (IBP) when applying the ASAS criteria (Hamilton et al, 2014) showed a 
minimum prevalence of IBP in a UK primary care population of 1.7%.
In patients with axSpA, the disease typically originates in the sacroiliac joints, then progresses to 
the spine. In the sacroiliac joints and the spine, active inflammation results in erosions, sclerosis, 
and fatty lesions. However, the most characteristic feature is new bone formation leading to 
ankylosis of the sacroiliac joints and syndesmophytes attached to the vertebral bodies. As a result 
of extended syndesmophyte formation, the spine may become fused over time. The majority of 
patients with axSpA have inflammatory back pain. Other objective signs of inflammation, such 
as enthesitis, dactylitis, peripheral arthritis, or uveitis; genetic features, such as the presence of 
human leukocyte antigen B27 (HLA-B27); and laboratory parameters, such as elevated CRP, 
may also be present (Braun, 2012; Rudwaleit et al, 2009a; Braun, 2007). Disability in axSpA is 
related to both the degree of inflammatory activity, causing pain, stiffness, fatigue, and poor 
quality of sleep, and to the degree of bony ankylosis, causing loss of spinal mobility.
The natural history of axSpA is characterized by a variable disease course. Over time, patients 
develop structural damage or radiographic abnormalities involving their sacroiliac joints and 
may fulfill the mNY criteria for AS. However, the rate of development of structural damage 
varies among patients (Rudwaleit, 2012). Some patients develop bilateral sacroiliitis, some 
unilateral sacroiliitis, and others may never develop definitive sacroiliitis on x-ray despite 
significant disease burden and other signs and symptoms of the disease, such as spinal lesions, 
uveitis, enthesitis, and peripheral arthritis. Approximately 10% of patients with nr-axSpA (25%, 
if CRP levels are elevated) develop definitive evidence of sacroiliitis on x-ray within 2 years 
(Sieper and van der Heijde, 2013c). 
Spondyloarthritides and inflammatory bowel disease (IBD) are chronic, idiopathic inflammatory 
disorders of, respectively, the axial and peripheral joints/entheses, and the intestinal tract, 
affecting up to 1% of our population. Typically, SpA manifests between adolescence and the age 
of 40. There is clinical and genetic evidence supporting some degree of overlap between the 
pathogenesis of these 2 entities. In SpA, microscopic gut inflammation can be present as an acute 
or a chronic inflammation. Normal histology of the gut or acute lesions, mimicking a bacterial 
colitis, were predominantly found in patients presenting with transient arthritis, whereas in 
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
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Page 19 of 173
patients with chronic intestinal lesions similar to Crohn’s disease (CD), a more persistent joint 
inflammation was perceived (Mielants et al, 1995). Microscopic gut inflammation was observed 
in about half of SpA patients originally in the 1980s and this prevalence has been confirmed in 
the Gent Inflammatory Arthritis and spoNdylitis cohort T (GIANT), which focused on new onset 
forms of SpA using the recently described ASAS classification criteria (Van Praet et al, 2013). 
Although about 6.5% of SpA patients evolved into IBD over 5 years, in patients exhibiting the 
chronic type of gut inflammation resembling Crohn’s disease, this number rose to 20%.
2.2
Burden of disease in axial spondyloarthritis
Axial SpA typically presents in patients <45 years of age, and these relatively young and 
otherwise healthy patients face a significant disease burden regardless of whether or not they 
have definitive evidence of sacroiliitis on x-ray. These patients experience substantial pain, 
prolonged, severe stiffness of joints, substantial sleep disturbances, reduced mobility and overall 
function, reduced quality of life (QoL), loss of productivity, and other disease-related symptoms 
(Huscher et al, 2006; Kobelt et al, 2006; Kobelt et al, 2004; Boonen et al, 2003; Boonen et al, 
2002; Ward, 2002). Moreover, studies have shown that the economic impact of the disease on 
society or patients can be substantial and that the costs are mainly driven by the costs associated 
with loss of work capacity (Kobelt et al, 2006; Kobelt et al, 2004; Boonen et al, 2003; Ward 
2002).
Several large observational and noninterventional cohort studies (Cuirea et al, 2013; Sieper et al, 
2013d) reported a similar burden of disease at study baseline across AS studies (captured through 
BASFI and BASDAI) and in nonradiographic axSpA and those with radiographic axSpA (AS) 
(captured through BASDAI). A literature review of clinical studies in both populations (Callhoff 
et al, 2014) and a confirmatory study (RAPID-AxSpA) (Landewe et al, 2014) confirmed this 
finding in the clinical study setting. 
2.3
Diagnosing axial spondyloarthritis in clinical practice
The diagnosis of AS and/or axSpA should be based on clinical assessments, considering typical 
signs and symptoms but also excluding other diseases that may have similar presentations. The 
mNY classification criteria, often used to support the diagnosis of AS, excludes patients whose 
sacroiliac joint (SIJ) x-rays do not have definitive evidence of sacroiliitis (Rostom, 2010). For a 
definitive classification of AS, the mNY classification criteria require radiographic evidence of 
sacroiliitis grade ≥2 bilaterally or sacroiliitis grade 3 to 4 unilaterally PLUS at least 1 of the 
following clinical criteria: low back pain and stiffness for ≥3 months, limitation of lumbar spine 
motion, or limitation of chest expansion. These criteria were designed for classification of 
patients in clinical studies rather than for diagnostic purposes. However, they have in fact been 
used for diagnosis resulting in diagnosis being delayed until irreversible structural damage 
documented on SIJ x-rays. Several publications have documented that the time from symptom 
onset to diagnosis of AS ranges from 5 to 10 years (Feldtkeller et al, 2003; Feldtkeller et al, 
2000; van der Linden et al, 1984a), thus demonstrating that radiographic or x-ray changes lag far 
behind other signs and symptoms.
Due to the problem of delayed disease recognition, ASAS recently developed new classification 
criteria for axSpA that do not require the presence of definitive sacroiliitis on x-ray, thus 
identifying a nr-axSpA subpopulation (Rudwaleit et al, 2009c; Rudwaleit et al, 2009d). These 
criteria establish standards that apply to patients with or without radiographic sacroiliitis, 
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enabling the conduct of clinical studies in patients with both nr-axSpA and AS. In patients with a 
history of chronic back pain for ≥3 months and age of onset <45 years, a classification of axSpA 
can be made based on either 1) current evidence of sacroiliitis on imaging (radiographs or MRI) 
plus ≥1 typical SpA feature or 2) the presence of HLA-B27 plus ≥2 typical SpA-features 
(Figure 2.1). In these criteria, sacroiliitis is defined as MRI evidence of sacroiliac joint 
inflammation or radiographic evidence of sacroiliitis meeting mNY classification criteria 
(Rostom, 2010).
Figure 2.1:
ASAS Classification criteria for axSpA
ASAS=Assessment of SpondyloArthritis International Society; axSpA=axial spondyloarthritis; CRP=C-reactive protein; 
HLA-B27=human leukocyte antigen B27; mNY=modified New York; MRI=magnetic resonance imaging; NSAID=nonsteroidal 
anti-inflammatory drug; SpA=spondyloarthritis. 
Source: Rudwaleit et al, 2009d 
2.4
Current management of axial spondyloarthritis
Based on the current treatment recommendations developed by ASAS and the European League 
Against Rheumatism (EULAR) for axSpA, first-line therapy consists of nonsteroidal 
anti-inflammatory drugs (NSAIDs) and nonpharmacologic treatment such as patient education 
and regular exercise/physiotherapy (Braun et al, 2011). NSAIDs are often initially rapidly 
effective for the symptoms pain and stiffness of axSpA (Poddubnyy, 2013; Poddubnyy et al, 
2012), but many patients lose symptomatic response and structural damage often progresses 
despite their use. Conventional disease-modifying antirheumatic drugs (DMARDs; eg, 
methotrexate [MTX] and sulfasalazine [SSZ]) have limited efficacy in axial disease, but may 
benefit patients with peripheral joint disease (Haibel et al, 2007; Braun et al, 2006; Haibel et al, 
2005). Therefore, DMARDs are recommended only in patients with predominantly peripheral 
manifestations (Braun et al, 2011). 
Patients who are intolerant of, or have inadequately responded to NSAIDs, or those in whom 
NSAIDs are contraindicated, have limited treatment options. Tumor necrosis factor alpha 
(TNFα) inhibitors (CZP, adalimumab [ADA], etanercept [ETN], infliximab [IFX], and 
golimumab [GOL]) are currently the only effective and approved treatment options. Infliximab 
and GOL are indicated for active AS only, while CZP, ADA, and ETN are indicated for 
nr-axSpA as an addition to the AS indication in several regions. 
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With the advent of the ASAS classification criteria for axSpA, several registration studies have 
been conducted in patients with nr-axSpA (Dougados et al, 2013; Sieper et al, 2013d) or axSpA 
(Landewe et al, 2014). These studies have found that anti-TNFs are effective in nr-axSpA 
patients, particularly in patients with objective signs of inflammation as defined by MRI 
positivity or CRP. The RAPID-axSpA study, the first axSpA study to enroll both AS and 
nr-axSpA patients, showed that baseline disease activity and treatment effect was similar 
between nr-axSpA and AS subjects (Landewe et al, 2014). In this study it was shown that CZP 
rapidly reduced the signs and symptoms of axSpA disease over 24 weeks of double-blind 
treatment in the broad axSpA population, including the AS and the nr axSpA subpopulations, 
and that the responses to the treatment were similar in both subpopulations (Landewe et al, 2014; 
Sieper and van der Heijde, 2013c) and maintained up to Week 96 (Mease et al, 2014; Sieper et al, 
2014).
Based on the results of the RAPID-axSpA study, CZP (Cimzia®) received approval in the EU 
and several other countries, eg, Turkey, Argentina, Russia, Chile, Switzerland, Hong Kong, 
Dominican Republic, Ecuador, and Peru, for the treatment of adult patients with severe active 
axSpA (comprising AS and nr-axSpA) and was approved for the treatment of adults with active 
AS in the USA, Canada, Australia, and also Malaysia.
Because of the therapeutic response in early disease, the ASAS consensus recommendation on 
the use of TNFα inhibitors in AS, updated in 2010, was extended to include the full spectrum of 
axSpA (van der Heijde, 2011).
2.5
Rationale
The demonstration of maintenance of response after reduction or even withdrawal of treatment 
would offer the physician and patient the opportunity to minimize the risks of anti-tumor 
necrosis factor (TNF) treatment while reducing healthcare costs. The data available to date 
suggest that anti-TNF therapy withdrawal in patients with active, nonradiographic, and/or early 
axSpA who are either in remission, or who have an ASAS40 response resulted in a flare (defined 
as loss of sustained remission, loss of ASAS40 response, or BASDAI >3 at 2 consecutive visits) 
in the majority (56 to 83%) of patients, resulting in the need to re-establish treatment (Haibel et 
al, 2013; Sieper et al, 2013a; Song et al, 2012). Publications that reported the effects of 
retreatment after a flare indicated that, in general, patients flaring responded well to retreatment. 
However, these studies did not provide information on questions such as whether there is an 
increased risk of immunogenicity following retreatment.
Available data suggest that the efficacy of anti-TNF treatment can be maintained even with 
reduction in dosage in a majority of patients with AS (Cantini et al, 2013; Olivieri et al, 2013). 
However, these studies suffer from several limitations and therefore there is a need to generate 
further robust data from prospective placebo-controlled, randomized studies to address the 
question of whether and in which patients dose reduction can be considered. 
The AS0005 study introduces both a full withdrawal arm (placebo) as well as a half-dose arm 
(CZP 200mg Q4W) to assess a potential differential effect between both active treatment arms 
(full-dose and half-dose) and placebo. Furthermore, it will also provide data on the efficacy and 
safety of retreatment after subjects experience a flare in disease activity.
The treatment of axSpA with TNF-inhibitors is known to also have some beneficial impact on 
extra-articular manifestations, like uveitis, psoriasis, and IBD. AS0005 will provide data on the 
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UCB
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Clinical Study Protocol
Certolizumab Pegol
AS0005
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Page 22 of 173
frequency and severity of these comorbidities in the study population and whether CZP can 
improve the signs and symptoms of both the extra-articular manifestations and axSpA at the 
same time. For axSpA patients suffering from gut inflammation, the QoL will be assessed with 
an inflammatory bowel disease questionnaire (IBD-Q) and, in addition to this, an analysis of 
calprotectin in stool and serum samples (a protein associated with acute gut inflammation) will 
be performed to assess the correlation between gut inflammation, quality of life, and response to 
treatment with CZP.
3
STUDY OBJECTIVES
The following key definitions are provided as a reference for understanding the study objectives 
and are used throughout the protocol.
Sustained remission is achieved when a subject has an ASDAS <1.3 at Week 32 or Week 36 (if 
ASDAS <1.3 at Week 32, it must be <2.1 at Week 36 [or vice versa]) and at Week 48. A subject 
is eligible for Part B of the study only if sustained remission is achieved in Part A.
A flare occurs when a subject has an ASDAS ≥2.1 at 2 consecutive visits or ASDAS >3.5 at any 
visit during Part B.
Subjects who meet the criteria of flare during Part B and who crossed-over to full-dose treatment 
(CZP 200mg Q2W) are regarded as escapers.
3.1
Primary objective
The primary objective of the study is to evaluate the percentage of subjects who do not 
experience a flare on CZP 200mg Q2W (full-dose) or 200mg Q4W (half-dose) as compared to 
placebo (CZP withdrawal) during Part B. 
3.2
Secondary objectives
The secondary objectives are to: 

Evaluate the percentage of subjects achieving sustained remission at the end of Part A

For subjects randomized into Part B:

Evaluate the time to flare and other measures of signs and symptoms

Compare the percentage of subjects who do not experience a flare between CZP full-dose 
and half-dose

Evaluate the efficacy of re-initiation of treatment with the CZP full-dose in subjects who 
experience a flare following a withdrawal or dose reduction of CZP

Assess safety and tolerability of CZP

Evaluate inflammatory changes over time as assessed by MRI
3.3
Other objectives
The other objectives are to evaluate: 

Physical function 

Signs and symptoms of the disease
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
Morning stiffness 

Fatigue 

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
Health-related QoL 

Work and household productivity 

Subject's health status

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Correlation of fecal calprotectin, serum calprotectin, IBD-Q and CRP
3.4
Pharmacokinetic, pharmacogenomic, and immunological 
objectives
Pharmacokinetic and immunological objectives are to follow the CZP concentrations throughout 
the study as well as the evolution of immunogenicity, respectively. Other pharmacogenomic 
objectives are:

Exploratory biomarkers and cytokines

Possible genetics, genomics, and proteomics 
4
STUDY VARIABLES
4.1
Efficacy variable
4.1.1
Primary efficacy variable
The primary efficacy variable is the percentage of subjects in Part B who do not experience a 
flare (refer to Section 3 for definition of flare).
4.1.2
Secondary efficacy variables
4.1.2.1
Secondary efficacy variables for subjects entering Part A

Percentage of subjects achieving sustained remission at Week 48

ASDAS disease activity (Ankylosing Spondylitis Disease Activity Score-Inactive Disease 
[ASDAS-ID], Ankylosing Spondylitis Disease Activity Score-Moderate Disease 
[ASDAS-MD], Ankylosing Spondylitis Disease Activity Score-High Disease activity 
[ASDAS-HD], and Ankylosing Spondylitis Disease Activity Score-very High Disease 
activity [ASDAS-vHD]) and clinical improvement (Ankylosing Spondylitis Disease Activity 
Score-Clinically Important Improvement [ASDAS-CII], Ankylosing Spondylitis Disease 
Activity Score-Major Improvement [ASDAS-MI]) at Week 48
4.1.2.2
Secondary efficacy variables for subjects entering Part B
The following are secondary efficacy variables for subjects entering Part B.

Time to flare 

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI) at Week 96
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Clinical Study Protocol
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AS0005
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Page 24 of 173

ASAS20, ASAS40, ASAS5/6, and ASAS PR response at Week 96

Change from Baseline in ASDAS, BASDAI, BASFI, and BASMI at Week 96

BASDAI50 response at Week 96

Change from Baseline in sacroiliac SPARCC and ASspIMRI-a in the Berlin modification 
scores at Week 96
4.1.2.3
Secondary efficacy variables for subjects who experience a flare in 
Part B
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated at Escape Week 12. 

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI)

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

Change from Baseline in ASDAS, BASDAI, BASFI, BASMI, and sacroiliac SPARCC and 
ASspIMRI-a in the Berlin modification scores.
4.1.3
Other efficacy variables 
4.1.3.1
Other efficacy variables for subjects entering Part A
The following other efficacy variables for subjects entering Part A will be evaluated at all 
scheduled study visits where the assessment is performed through Week 48.

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

BASDAI50 response

Change from Baseline in ASDAS, BASDAI, and BASMI

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI)

Change from Baseline in sacroiliac SPARCC and ASspIMRI-a in the Berlin modification 
scores 

Change from Baseline in all individual ASAS core components

Patient’s Global Assessment of Disease Activity (PtGADA)

Total spinal pain (Numeric Rating Scale [NRS])

BASFI

Average of Questions 5 and 6 of the BASDAI concerning morning stiffness

Change from Baseline in nocturnal spinal pain (NRS)

Change from Baseline in spinal mobility, as assessed by occiput to wall distance 

Change from Baseline in spinal mobility as assessed by chest expansion

Change from Baseline in PhGADA
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
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Page 25 of 173

Change from Baseline in Fatigue (NRS) (from BASDAI) 

Change from Baseline in CRP 

Change from Baseline in ASQoL 

Change from Baseline in Work Productivity Survey (WPS) 

Health status as assessed by the EuroQoL Health Status Questionnaire 5 dimensions 
(EQ-5D): domains, visual analog scale (VAS) actual score and change from Baseline in VAS 
score

Change from Baseline in Maastricht Ankylosis Spondylitis Enthesitis Score (MASES)

Change from Baseline in swollen and tender joint counts (44 joint count)

Number of uveitis flares

Number of IBD exacerbations 

Change from Baseline in fecal calprotectin

Change from Baseline in serum calprotectin

Change from Baseline in the IBD-Q

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP

Number of psoriasis exacerbations (in subjects with concurrent psoriasis)

Change from Baseline in all Short-Form 36-Item Health Survey (SF-36) domains, SF-36 
Physical Component Summary (PCS), and SF-36 Mental Component Summary (MCS)

Resources utilization: concomitant medical procedures, healthcare provider consultations not 
foreseen by the protocol, hospitalizations/emergency room visits
4.1.3.2
Other efficacy variables for subjects entering Part B
The following other efficacy variables for subjects entering Part B will be evaluated at all 
scheduled study visits where the assessment is performed following the first administration of 
study medication in Part B.

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

BASDAI50 response

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI)

Change from Baseline in ASDAS, BASDAI, and BASMI

Change from randomization Baseline (Week 48) in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in all individual ASAS core components

PtGADA
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Total spinal pain (NRS)
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 26 of 173

BASFI

Average of Questions 5 and 6 of the BASDAI concerning morning stiffness

Change from Baseline in nocturnal spinal pain (NRS)

Change from Baseline in spinal mobility, as assessed by occiput to wall distance

Change from Baseline in spinal mobility assessed by chest expansion

Change from Baseline in PhGADA
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Change from Baseline in Fatigue (NRS) (from BASDAI) 

Change from Baseline in CRP 
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Change from Baseline in ASQoL
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Change from Baseline in sacroiliac SPARCC and ASspIMRI-a in the Berlin modification 
scores
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Change from randomization Baseline (Week 48) in sacroiliac SPARCC and spine 
ASspIMRI-a in the Berlin modification scores
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Change from Baseline in WPS 
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Health status as assessed by the EQ-5D: domains, VAS actual score, and change from 
Baseline in VAS score
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Change from Baseline in MASES
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Change from Baseline in swollen and tender joint counts (44 joint count)

Number of uveitis flares

Number of inflammatory bowel disease exacerbations

Change from Baseline in fecal calprotectin

Change from Baseline in serum calprotectin

Change from Baseline in the IBD-Q

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP

Number of psoriasis exacerbations (in subjects with concurrent psoriasis)

Change from Baseline in all SF-36 domains, SF-36 PCS, and SF-36 MCS

Resources utilization: concomitant medical procedures, healthcare provider consultations not 
foreseen by the protocol, hospitalizations/emergency room visits
4.1.3.3
Other efficacy variables for subjects who experience a flare in Part B
The following other efficacy variables for subjects who experience a flare in Part B will be 
evaluated at all scheduled study visits where the assessment is performed following Escape 
Week 0.
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Page 27 of 173

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI) 

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

Change from Baseline in ASDAS, BASDAI, and BASMI

Change from randomization Baseline (Week 48) in ASDAS, BASDAI, BASFI, and BASMI

Change from the visit at which the flare occurred in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in all individual ASAS core components

PtGADA

Total spinal pain (NRS)

BASFI
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Average of Questions 5 and 6 of the BASDAI concerning morning stiffness

Change from Baseline in nocturnal spinal pain (NRS)

Change from Baseline in spinal mobility, as assessed by occiput to wall distance

Change from Baseline in spinal mobility assessed by chest expansion

Change from Baseline in PhGADA

Change from Baseline in Fatigue (NRS) (from BASDAI) 

BASDAI50 response

Change from Baseline in CRP 

Change from Baseline in ASQoL

Change from Baseline in sacroiliac SPARCC and ASspIMRI-a in Berlin modification scores

Change from randomization Baseline (Week 48) in sacroiliac SPARCC and ASspIMRI-a in 
Berlin modification scores

Change from Escape Week 0 in sacroiliac SPARCC and ASspIMRI-a in Berlin modification 
scores

Change from Baseline in WPS 

Health status as assessed by the EQ-5D: domains, VAS actual score, and change from 
Baseline in VAS score

Change from Baseline in MASES

Number of uveitis flares

Number of IBD exacerbations

Change from Baseline in fecal calprotectin

Change from Baseline in serum calprotectin
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
Change from Baseline in the IBD-Q

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP

Number of psoriasis exacerbations (in subjects with concurrent psoriasis)

Change from Baseline in all SF-36 domains, SF-36 PCS, and SF-36 MCS

Resources utilization: concomitant medical procedures, healthcare provider consultations not 
foreseen by the protocol, hospitalizations/emergency room visits
4.2
Pharmacokinetic and pharmacogenomic variables
4.2.1
Pharmacokinetic variables
Plasma concentrations of CZP will be measured at Baseline and subsequent timepoints as 
described in Table 5.1 and Table 5.2. These plasma samples may be used additionally for 
analyses of CZP and its constituent moieties using alternative methods.
4.2.2
Biomarkers
Selected samples collected for measurement of CZP plasma concentration may be used 
additionally for analyses of biomarkers and cytokines. These analyses may include, but are not 
limited to: Matrix metalloproteinase-3 (MMP-3); bone morphogenic protein (BMP) BMP-2, -4
and -7, wingless-related mouse mammary tumor virus integration site protein (WNT1), Inducible 
Signaling Pathway proteins (WISP), Gremlin, Dickkopf-related protein 1 (DKK1), Sclerostin, 
Hedgehog proteins (Shh, Ihh, Dhh), Collagen turnover/cleavage products, collagen type X, 
vascular endothelial growth factor (VEGF), citrullinated vimentin fragments, cytokines: IL13, 
IL17 A and F, IL23, IL34, Transforming Growth Factor (TGF)β, Macrophage colony-
stimulating factors (M-CSF), Granulocyte macrophage colony-stimulating factor (GM-CSF, 
CSF-1, soluble CSF-1 Receptor (sCSF1r) levels.
4.2.3
Pharmacogenomic variables
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline, 
and, for genomic and proteomics analysis only, additionally at Weeks 12, 24, 48, 72, and 96/WD
to enable exploratory evaluation of biomarkers relative to drug treatment and inflammatory and 
immune response processes. The samples will be stored at -80°C at the Central Biorepository for 
up to 20 years or according to local laws.
4.3
Immunogenicity variables
Anti-CZP antibody (ADAb) levels will be assessed at Baseline and subsequent timepoints as 
described in Table 5.1 and Table 5.2.
Determination of ADAb will be done using a validated screening, confirmation, and titration 
ADAb bridging assay, with potential further characterization by a neutralizing antibody (NAb) 
assay. The immunogenicity data will be processed according to dedicated Bioanalytical Analysis 
plans.
4.4
Safety variables
Safety variables to be assessed are AEs, physical examination, vital sign measurements, chest 
x-ray, and measurements of laboratory parameters (hematology, biochemistry, and urinalysis). 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 29 of 173
Adverse events will be solicited at every visit, and recorded and coded according to the latest 
version of the Medical Dictionary for Regulatory Activities® criteria used at UCB at the time of 
analysis.
Physical examination findings will be recorded in the electronic Case Report Form (eCRF) only 
at Screening. Clinically relevant changes in subsequent physical examinations will be recorded 
as AEs.
Clinical laboratory values (hematology, biochemistry, and urinalysis) will be collected and 
assessed at Screening, Baseline, at Weeks 12, 24, 32, 36, and every 12 weeks thereafter through 
to study Week 96/WD Visit and at the SFU Visit 10 weeks after the last dose of study
medication. C-reactive protein values will be collected and assessed at Screening, Baseline, 
Weeks 2, 4, 12, 24, 32, 36, 3 to 5 days prior to Week 48, Week 50, Week 52, and every 4 weeks 
thereafter through to study Week 96/WD Visit. For escapers, different schedules for clinical 
laboratory values and CRP apply after start of the escape treatment (refer to Table 5.2).
At Screening, Week 48, and Week 96, all subjects will have an IGRA test (QuantiFERON TB 
GOLD In Tube test or another WHO-validated IGRA test such as Elispot, if QuantiFERON TB 
GOLD In Tube test is not available locally). A chest x-ray (or, if done, computed axial 
tomography of the chest) at Screening (or up to 3 months prior to Screening) must be read and 
reported consistent with standard clinical reporting practice by an experienced TB specialist, 
radiologist or a pulmonologist, who is specifically required to look for signs of active TB or 
signs of past/inactive TB infection. The official report of the imaging must specifically indicate 
the absence of findings suggestive of current active TB or prior inactive TB. In addition to a 
physical examination done intermittently throughout the study, subjects will be evaluated at 
Screening, Baseline, and every 12 weeks thereafter, including the Week 96/WD Visit, for signs 
and symptoms of latent or active TB infection and risk factors for exposure to TB using the TB 
questionnaire.
5
STUDY DESIGN
5.1
Study description
Study AS0005 is a multicenter, open-label (Part A) followed by a randomized, double-blind, 
parallel-group, placebo-controlled clinical study (Part B) to evaluate the efficacy, safety, PK, and 
immunogenicity of CZP in adult subjects with axSpA in sustained remission who continued 
either on full-dose treatment (CZP 200mg Q2W), on a dose reduction (CZP 200mg Q4W), or 
withdrawal of CZP treatment.
The study includes 2 parts, A and B, as follows (a schematic diagram is provided in Figure 5.1
and the schedule of study assessments is in Table 5.1 and Table 5.2).
5.1.1
Part A
Period 1 (Screening Period): Up to 5 Weeks before Baseline
Eligible subjects will be informed about the study and sign the informed consent. Concomitant 
medications such as MTX, SSZ, hydroxychloroquine (HCQ), NSAIDs, and corticosteroids, will 
be verified and, if required, the washout of any medications not permitted for use during the 
study will be started. Concomitant medications must follow the protocol requirements in 
Table 6.1. Subjects will receive a physical examination and vital signs measurements will be 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 30 of 173
taken. Women of childbearing age will be tested for pregnancy. Laboratory data (hematology, 
urine, and biochemistry tests) and treatment of latent TB (LTB), where necessary, will be 
collected. Subjects must undergo a TB test and complete a TB questionnaire. Patient’s Global 
Assessment of Disease Activity, BASDAI, BASMI, spinal mobility assessments, and MRI will 
be performed. Additionally, a central reading of the x-ray will define the stratification of the
subjects into the nr-axSpA or the AS subpopulation. 
Period 2 (Open-Label Period): Week 0 (Baseline) to Week 48 
Eligible subjects will receive 3 loading doses of CZP sc 400mg at Weeks 0, 2, and 4 followed by 
CZP 200mg Q2W. 
All subjects will be trained on self-administration at Weeks 2 and 4. Subjects will self-administer 
starting from Week 6. At Weeks 12, 24, 32, 36, 3 to 5 days prior to Week 48 Visit and Week 48 
in Period 2, subjects will visit the site and undergo relevant tests and assessments according to 
Table 5.1. The injection schedule (Figure 7.1) will provide the sequence of self-administration 
and site visits including administration at the site.
All subjects who have not achieved sustained remission at the end of Period 2 (Week 48) will be 
discontinued from the study and treated at the discretion of their physician. Those subjects who 
discontinue prematurely from the study for any reason will be treated at the discretion of their 
physician.
5.1.2
Part B
Period 3 (Double-Blind Period): Week 48 to Week 96, placebo-controlled 
Subjects must meet the sustained remission criteria as defined in Section 3 in order to be 
randomized to Part B. 
Subjects in sustained remission will be randomized in a 1:1:1 ratio to the following treatment 
arms:

CZP administered sc at a dose of 200mg Q2W (full-dose)

CZP administered sc at a dose of 200mg Q4W (half-dose)

Placebo
To maintain the study blind during Part B, study medication administration will be done by a 
dedicated trained unblinded study team at each site. In order to reduce the number of onsite visits 
for the subjects, where possible, a home nurse service will be offered. Home nurses, who will be 
responsible for administering the study medication at the subject's home, will be unblinded.
All subjects who discontinue prematurely from the study for any reason during the Double-Blind 
Period will be treated at the discretion of the Investigator. 
The last dosing visit will be performed according to the dosing schedule in Table 5.1. The final 
study assessments will be performed at Week 96. Subjects experiencing a flare during the 
Double-Blind Period will receive escape treatment as defined in Section 5.1.3. 
Stool samples for fecal calprotectin will be collected for all subjects at Weeks 48 and 96/WD and 
blood samples for serum calprotectin will be collected for all subjects 3 to 5 days prior to 
Week 48, Week 72, and at Week 96/WD.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 31 of 173
Period 4 (SFU Period): 10 weeks after the last dose of study medication
All subjects, including those withdrawn from study treatment, will have a SFU Visit 10 weeks 
after their last dose of study medication.
5.1.3
Escape treatment
Subjects receiving placebo or half-dose CZP who experience a flare during the Double-Blind 
Period will escape to full-dose treatment until the end of that period or for at least 12 weeks, 
whichever is longer. Subjects who experience a flare while on CZP full-dose will continue to 
receive CZP full-dose (see details in Section 6.3.2). The interactive voice or web response 
system (IXRS) will be used to determine whether flare criteria are met.
The schedule of study assessments for subjects experiencing a flare in Part B is provided in 
Table 5.2.
5.1.4
Study duration per subject
For each subject, the study will last a maximum of 109 weeks, as follows:

Up to 5 weeks of Screening Period

48 weeks in the Open-Label Period

48 weeks in the Double-Blind Period (dose reduction/withdrawal of CZP-treatment) 

A SFU Visit 10 weeks after last dose administration (Period 4).
Of the 10 weeks interval specified for the SFU Visit, the first 2 weeks coincide with the last 
2 weeks of the Double-Blind Period (ie, last 2 weeks of the 48 weeks) and the last administration 
is at Week 94. Hence, the maximum duration is 109 weeks. 
For subjects who experience a flare during the Double-Blind Period, the study duration might be 
prolonged (refer to Section 6.3.2).
The end of the study is defined as the date of the last visit (SFU) of the last subject in the study.
5.1.5
Planned number of subjects and sites
Approximately 1250 subjects will be screened in order to enroll 750 subjects into Part A, where 
210 subjects are expected to meet the sustained remission criteria and be eligible for 
randomization into Part B. Ankylosing Spondylitis Disease Activity Score will be closely 
monitored during Part A of the study to project the percentage of enrolled subjects likely to 
achieve sustained remission at the end of Part A. The enrollment will be adjusted accordingly in 
order to achieve the required number of 210 subjects in sustained clinical remission qualifying 
for Part B. 
It is planned to enroll subjects at approximately 95 sites.
5.1.6
Anticipated regions and countries
The study will be conducted in North America, Europe, Asia, and other regions as appropriate.
5.2
Schedule of study assessments
The schedule of study assessments for all subjects completing Part A and Part B of the study is 
presented in Table 5.1.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 32 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
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MRI l
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 33 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
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spinal pain
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 34 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
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weeks
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 35 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Check of sustained 
remission criteria r
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone Contact s
X
X
X
X
Abs=antibodies; ADAb= anti-CZP antibody; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing Spondylitis Quality of Life; axSpA=axial 
spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath 
Ankylosing Spondylitis Metrology Index; CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site 
visit; HIV=human immunodeficiency virus; HLA-B27=human leukocyte antigen B27; HN=home nurse visit at subject’s home; IBD=Inflammatory bowel 
disease; incl.=including; inj=injection; IXRS=Interactive Voice or Web Response System; MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; 
MRI=magnetic resonance imaging; PE=physical exam; sc=subcutaneously; SF-36=Short‑Form 36‑item Health Survey; SFU=Safety Follow-Up; SI=sacroiliac; 
subj=subject; TB=tuberculosis; W=Week; WD=Withdrawal; WHO=World Health Organization
a Assessments conducted 3 to 5 days prior to Week 48 will serve as the qualification assessments for subjects determined to be eligible for randomization into 
Part B at Week 48.
b SFU: 10 weeks after last dose of study medication.
c Informed consent: Prior to any study activities, subjects will be asked to read and sign the informed consent form for the conduct of the study. A separate 
informed consent form will be obtained from subjects consenting also to the use of their blood samples for possible genetic, genomic, and proteomic analysis.
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening and Baseline, thereafter pulse rate, systolic 
and diastolic blood pressures and temperature are to be measured. If a subject experiences an AE, respiration rate will be measured in addition. 
e Testing to rule out hepatitis B surface antigen, antibodies to hepatitis C, antibodies to HIV and HLA-B27 at Screening only.
f To be assessed as indicated and from Week 52 onwards every 4 weeks only.
g Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and SFU and urine testing at Baseline and Week 96/WD 
Visit.
h Includes evaluation of signs and symptoms of active TB and risk factors for exposure to TB. Weight is to be measured at Screening, Baseline, Week 48, and at 
Week 96/WD. Height will be measured at the Baseline Visit only.
i Screening chest x-ray must have occurred within 3 months prior to Screening or during Screening, and should be repeated only if the TB test was confirmed 
positive or any further evidence is suggestive of potential TB infection (eg, exposure).
j QuantiFERON TB GOLD test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB GOLD test is not locally available. The TB test 
will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for subjects with previously negative TB test result.
PY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 36 of 173
k Sacroiliac joint x-rays will be performed at Screening and used as the Baseline assessment for all subjects. An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit may be used as the Baseline assessment provided that the film can be submitted and meets the requirements for central reading.
l Magnetic resonance imaging of the spine and sacroiliac joints to be performed at Screening, and within a ± 2 weeks time window at Weeks 48 and 96 or WD 
Visit if the last MRI was performed more than 12 weeks prior to WD Visit.
m Kit for collection of stool sample to be provided at Screening Visit. Stool sample shall be obtained prior to Baseline and provided to the Investigator at the 
Baseline Visit.
n Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal flexion, cervical rotation, tragus to wall distance, 
and maximal intermalleolar distance.
o Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by the protocol, hospitalizations/emergency 
room visits.
p Prior medication will be at Screening only.
q Nurse visit at home only where approved and with agreement of subjects. Otherwise, the visit procedures will be done onsite by the site staff.
r Refer to Protocol Section 3 for definition. In case of loss of sustained remission in Part B, the subject must visit the study site for the next scheduled dose of 
study medication. The Investigator will initiate the escape treatment as appropriate. Refer to Table 5.2 for details.
s Subjects will be contacted by telephone about every 4 weeks in between the onsite visits.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 37 of 173
Subjects experiencing a flare in Part B will be invited for an onsite visit to receive the next 
planned dose of investigational product (escape treatment). This visit will take place 2 weeks 
after the last assessment that resulted in meeting the flare criteria; or, at the discretion of the 
Investigator, at an earlier timepoint. As the start of escape treatment may vary from subject to 
subject, it will be referred to as “Escape Week 0” in Table 5.2. Subjects will remain on the 
escape treatment for at least 12 weeks or until Week 96 of the regular visit schedule as described 
in Table 5.1, whichever is longer.
The assessment schedule for subjects experiencing a flare in Part B will start 2 weeks after the 
flare condition is confirmed and will end 2 weeks before Week 96 after Baseline of the regular 
assessment schedule (Table 5.2). If the flare occurs late in Part B (at or after Week 82), the 
subject must receive the escape treatment for 12 weeks (eg, starting at Week 84 until Week 96). 
The final assessments at study end (as laid down for Week 96) must be performed 2 weeks after 
the last study dose administration (Table 5.1).
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Vital signs d
X
X
X
X
Hematology/urine/ biochemistry
X
X
CRP e
X
X
X
X f
X
X f
Stool sample g
X
X
Serum calprotectin g
X
X
IBD-Questionnaire g
X
X
PE
X
X
X
X
Extra-articular assessments
X
X
X
MRI h
X
X
TB questionnaire
X
X
BASMI & Spinal mobility i
X
X
X
X
BASDAI
X
X
X
X f
X
X f
BASFI
X
X
X
X
SF-36
X
X
X
AsQoL
X
X
X
X
EQ-5D
X
X
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 38 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
MASES
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
Patient’s Global Assessment of Disease Activity
X
X
X
X f
X
X f
Physician’s Global Assessment of Disease Activity
X
X
X
X
Work Productivity Survey
X
X
X
Resources utilization j
X
X
X
CZP plasma concentration/ADAb
X
X
X
X
Biomarker
X
X
X
X
Concomitant medication
X
X
X
X
AEs
X
X
X
X
IXRS
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
Study drug sc self-inj. at home
X
X
Telephone Contact k
X
X
Abs=antibodies; ADAb=anti-CZP antibody; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing 
Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath 
Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; CRP=C-reactive 
protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site visit; HN=home 
nurse visit at subjects home; IBD=Inflammatory bowel disease; IXRS=Interactive Voice or Web Response System; 
MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; MRI=magnetic resonance imaging; PE=physical exam; 
sc=subcutaneously; SF-36=Short-Form 36-item Health Survey; TB=tuberculosis; W=Week
a HN Q4W only for obtaining blood sample (CRP) and electronic patient reported outcome (ePRO) data as 
indicated 
b Schedule onsite visit every 12 weeks until Week 96 of regular visit schedule is reached. For example, at Weeks 74 
and 86, if start of escape treatment is at Week 62 (=Escape Week 0). At Week 96 and SFU, perform assessments 
as described in Table 5.1. For subjects experiencing a flare at/after Week 82, escape treatment should be provided 
for 12 weeks and the subject invited for the final assessment visit (as laid down for Week 96) 2 weeks later 
c Until 2 weeks before Week 96 of regular visit schedule is reached
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening 
and Baseline, thereafter pulse rate, systolic and diastolic blood pressures and temperature are to be measured. If a 
subject experiences an AE, respiration rate will be measured in addition
e To be assessed as indicated and from Week 52 onwards every 4 weeks only
f To be assessed every 4 weeks only (Weeks 8, 12, 16, 20, 24, … up to Week 96)
g To be assessed at escape Weeks 0 and 12 only
CTED COPY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 39 of 173
h To be performed at escape Weeks 0 and 12 only and at final assessment visit at Week 96, if the last MRI was done 
at least 12 weeks prior to Week 96. Magnetic resonance imaging is to be performed within
a ±2 weeks time window.
i Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal 
flexion, cervical rotation, tragus to wall distance, and maximal intermalleolar distance.
j Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by 
the protocol, hospitalizations/emergency room visits
k Subjects will be contacted by telephone about every 4 weeks in between the onsite visits
5.3
Schematic diagram
Figure 5.1:
Schematic diagram
axSpA=axial spondyloarthritis; CZP=certolizumab pegol; Q2W=every 2 weeks; Q4W=every 4 weeks; 
SFU=Safety Follow-Up
5.4
Rationale for study design and selection of dose
There are limited data around the optimal duration of treatment in patients with early axSpA and 
whether it is appropriate to withdraw or reduce treatment at some point in patients who are in 
remission or low disease activity. The data available to date suggest that anti-TNF therapy 
withdrawal in patients with active, nonradiographic, and/or early axial spondyloarthritis who are 
either in remission, or who have an ASAS40 response resulted in a flare (defined as loss of 
sustained remission, loss of ASAS40 response, or BASDAI >3 at 2 consecutive visits) in the 
majority (56 to 83%) of patients, resulting in the need to re-establish treatment (Song, 2012; 
Haibel, 2013; Sieper et al, 2013a). Publications that reported the effects of retreatment after a 
flare indicated that, in general, patients flaring responded well to retreatment. However, these 
studies did not provide information on aspects such as whether there is an increased risk of 
immunogenicity following retreatment. The efficacy of anti-TNF treatment can be maintained 
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 40 of 173
with reduction in dosage in a majority of patients with AS (Cantini et al, 2013; Olivieri et al, 
2013). However, there is currently limited evidence related to the impact of dose reduction in 
patients with early axSpA.
The dose of CZP that will be used in this study is 200mg Q2W with a loading dose of CZP 
400mg at Weeks 0, 2, and 4. Although there are 2 approved doses for rheumatologic disease in
most regions around the world (loading dose of 400mg CZP at Weeks 0, 2, and 4 followed by 
CZP 200mg Q2W; 400mg Q4W can be considered), the CZP 200mg Q2W dose is the dose most 
frequently prescribed around the world. Thus, using the 200mg Q2W dose in this study will 
provide treating physicians around the world the opportunity to compare the study results with 
the dose they are most likely to use in their daily practice.
In order to ensure that subjects in the placebo arm or 200mg Q4W arm are not deprived of 
therapy in case of deterioration of their signs and symptoms, they will be offered escape 
opportunities to full-dose treatment (CZP 200mg Q2W) during the Double-Blind Period until the 
end of that period or for at least 12 weeks, whichever is longer.
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 or by the parent(s) or legal 
representative. 
2. Subject/legal representative is considered reliable and capable of adhering to the protocol 
(eg, able to understand and complete diaries), visit schedule, or medication intake according 
to the judgment of the Investigator.
3. Subject is at least 18 years old and not older than 45 years at the start of Screening Visit.
4. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of 
childbearing, or effectively practicing an acceptable method of contraception (including 
oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and 
spermicide). Abstinence only is not an acceptable method. Subjects must agree to use 
adequate contraception during the study; and after the last dose of study treatment for at least 
10 weeks (or - for participating countries of the European Union - 5 months in accordance 
with the Summary of Product Characteristics [SmPC]) or longer, if required by local 
regulations after the last dose of study treatment. Male subjects must agree to ensure that also
their female partner(s) use adequate contraception during the study and for at least 10 weeks
(or - for participating countries of the European Union - 5 months in accordance with the 
SmPC) or longer, if required by local regulations after the subject receives their last dose of 
study treatment.
5. Subjects must have a documented diagnosis of adult-onset axSpA with at least 3 months' 
symptom duration and meet the ASAS classification criteria for axSpA (according to 
Appendix 18.1) and symptom duration of less than 5 years prior to the participation of this 
study. 
6. Subjects must have active disease at Screening as defined by 
REDACTED COPY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 41 of 173

ASDAS score ≥2.1 

BASDAI score ≥4

Spinal pain ≥4 on a 0 to 10 NRS (from BASDAI Item 2)

for mNY-negative subjects only: CRP> upper limit of normal (ULN) and/or current 
evidence for sacroiliitis on the Screening MRI as defined by a ASAS/Outcome Measures 
in Rheumatology Clinical Trials (OMERACT) SI-MRI score ≥2 and confirmed by 
central reading
7. Subjects must have had an inadequate response to, have a contraindication to, or have been 
intolerant to at least 2 NSAIDs. Inadequate response to an NSAID is defined as lack of 
response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the 
administered NSAID.
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Subject has previously participated in this study or subject has previously been assigned to 
treatment in a study of the medication under investigation in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP) (or a 
medical device) within the previous 3 months (or five half-lives whichever is greater) or is 
currently participating in another study of an IMP (or a medical device). 
3. Subject has history of chronic alcohol abuse or drug abuse within the last year.
4. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the subject's ability to participate in this study.
5. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as 
stated in this protocol.
AxSpA disease-related exclusions
6. Subjects must not have fibromyalgia or total spinal ankylosis ("bamboo spine"), or any other 
inflammatory arthritis, eg, RA, systemic lupus erythematosus, sarcoidosis.
7. Subjects must not have a secondary, noninflammatory condition (eg, osteoarthritis) that in 
the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of 
study medication on the subject's primary diagnosis of axSpA.
Prior medications exclusions
8. Subjects must not have used the following medications in the manner as detailed by the 
Exclusion Criteria in the following table.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 42 of 173
Table 6.1:
Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
Study Visits
Analgesics (including, but 
not limited to 
acetaminophen, 
paracetamol, opiates, or 
combinations thereof)
Up to maximum approved 
dose 
Any change in stable dose 
regimen is excluded in the 
14 days prior to the 
Baseline Visit.
Any ad hoc (prn) use of 
analgesics is not permitted 
within 24 hours prior to 
any postscreening visit.
Stable dose of analgesics 
(including narcotics) are 
permitted throughout the 
study.
NSAIDs (including 
cyclooxygenase 2 
[COX 2] inhibitors) 
Up to maximum approved 
dose regimen 
Any change in stable dose 
regimen is excluded in the 
14 days prior to the 
Baseline Visit.
Any ad hoc (prn) use of 
NSAIDs is not permitted 
within 24 hours prior to 
any postscreening visit.
NSAID dose can be 
down-titrated at 
Investigator discretion, if 
clinically indicated, until 
Week 28, after which 
NSAID treatment should 
remain as stable as 
possible.
NSAID dose should be 
stable until Week 96 (if 
subjects have to decrease 
or stop taking medication 
due to safety reasons, they 
may reduce their dose and 
continue in the study).
Oral corticosteroids 
Maximum allowed ≤10mg 
daily total prednisone 
equivalent a
Any change in stable dose 
used for axSpA in the 28 
days prior to the Baseline 
Visit.
A change in the dose is not 
allowed until Week 96.
Oral corticosteroid tapers 
of less than 14 days used 
to treat other indication 
(asthma exacerbation, 
contact dermatitis, etc) are 
allowed as long as the 
maximum daily dose is 
≤20mg. The taper must 
end at least 1 week before 
study visit.
Intramuscular (im) 
corticosteroids
Any dose
Use in the 28 days prior to 
the Baseline Visit.
Intramuscular 
corticosteroids must not be 
used during the study.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 43 of 173
Table 6.1:
Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
Study Visits
Intra-articular (ia) 
corticosteroids 
Up to maximum approved 
dose 
Use in the 28 days prior to 
the Baseline Visit.
SIJ ia corticosteroid 
injections are not allowed 
during the study.
Peripheral joint injections 
are permitted.
Intravenous (iv) 
corticosteroids
Up to maximum approved 
dose
Use in the 28 days prior to 
the baseline Visit.
iv doses of corticosteroids 
may be used during the 
study for acute illnesses as 
long as the dose is not 
given within 1 week prior 
to Week 12, Week 24, 
Week 48, or Week 96 and 
the underlying disease 
does not present a 
contraindication to the 
subject remaining in the 
study. Indications might 
include dermatitis, 
gastroenteritis, asthma 
exacerbation, and 
pneumonia.
Hyaluronic acid (ia)
Any dose
Use in the 28 days prior to 
the Baseline Visit. 
After Baseline ia injection 
of hyaluronic acid may be 
used in the knee.
SAARDsb:
SSZ and/or HCQ and/or 
MTX and/or LFN and /or 
AZA
Maximum allowed:
SSZ ≤3g daily
HCQ ≤400mg daily 
MTX ≤25mg weekly
AZA ≤150mg/day
LFN ≤20mg/day
SAARD use initiated 
and/or any change in the 
dose regimen in the 28 
days prior to the Baseline 
Visit. 
No change is permitted in 
the route of administration 
for MTX (im, sc, or oral) 
in the 28 days prior to the 
Baseline Visit
SAARDs should be stable 
until Week 96 (if a subject 
has to decrease or stop 
taking medications due to 
safety reasons, they may 
reduce their SAARDs and 
continue in the study).
SAARDs:
Cyclosporine, 
Cyclophosphamide, 
Mycophenolic acid, 
Apremilast
Up to maximum approved 
dose
Use within 28 days prior to 
the Baseline Visit. 
Must not be started during 
the study.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 44 of 173
Table 6.1:
Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
Study Visits
Anti-TNF therapies:
IFX
ADA
ETN
GOL
CZP
Any dose
For IFX, ADA, and GOL, 
any use within the 3 
months prior to the 
Baseline Visit.
For CZP any exposure 
history. 
For ETN, use within the 28 
days prior to the Baseline 
Visit.
Only 1 previous biologic is 
allowed.
Must not be started during 
the study.
Other rheumatologic 
therapies:
Abatacept
tocilizumab
ustekinumab
tofacitinib
Rituximab or other anti-
CD20 antibodies
Any dose
Any exposure history.
Must not be started during 
the study.
Osteoporosis Medications:
Risedronate, Alendronate, 
Ibandronate
Denosumab
Cathepsin K inhibitor
Cinacalcet
Calcitonin
Up to maximum approved 
dose
All stable osteoporosis 
medications are permitted 
except for iv 
bisphosphonates.
Osteoporosis medications 
with the exception of iv 
bisphosphonates are 
allowed without 
restriction. 
iv bisphosphonates are not 
permitted any time within 
the study.
Intravenous 
Bisphosphonates:
Zoledronic acid
Ibandronate
Pamidronate
Any dose
Zoledronic acid: any use 
within the 3 years prior to 
randomization
Ibandronate or 
pamidronate: any use 
within the past 2 years.
If iv bisphosphonate 
treatment is initiated 
during the study, the 
subject should be 
discontinued from study 
medication.
ADA=adalimumab; AZA=azathioprine; axSpA=axial spondyloarthritis; CD20=Cluster of Differentiation 20; 
COX 2=cyclooxygenase 2; CZP=certolizumab pegol; ETN=etanercept; GOL=golimumab; 
HCQ=hydroxychloroquine; IFX=infliximab; ia=intra-articular; im=intramuscular; iv=intravenous; 
LFN=leflunomide; MTX=methotrexate; NSAID=nonsteroidal anti-inflammatory drug; prn=pro re nata (as needed); 
RA=rheumatoid arthritis; SAARD=slow acting antirheumatic drug; SIJ=sacroiliac joint; SSZ=sulfasalazine
a A table of corticosteroid equivalent doses is provided in Table 18.1 (Appendix 18.2)
b Throughout the table, we refer to compounds such as sulfasalazine and methotrexate as SAARDs (slow-acting 
antirheumatic drugs). These medications are also commonly referred to as DMARDs, but since there is no 
evidence that they are in fact disease-modifying in axSpA (unlike in RA), we have opted for the more appropriate 
SAARD terminology.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 45 of 173
Previous clinical studies and previous biological therapy exclusions
9. Subjects must not have received any nonbiological therapy for axSpA not listed above within 
or outside a clinical study in the 3 months or within 5 half-lives prior to the Baseline Visit 
(whichever is longer). 
10. Subjects must not have received any experimental biological agents (defined as those agents 
unlicensed for use in axSpA in Europe or the USA).
11. Subjects must not have received previous treatment with a polyethylene glycolylated 
(PEGylated) compound that resulted in a severe hypersensitivity reaction or an anaphylactic 
reaction.
12. Subjects may not have been exposed to more than 1 TNF antagonist prior to the Baseline 
Visit and may not be a primary failure to TNF antagonist therapy (defined as no response 
within the first 12 weeks of treatment with the TNF antagonist).
Medical History Exclusions
13. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 10 weeks (or – for participating countries of the EU – 5 months in accordance 
with the SmPC) following the last dose of the investigational product.
14. Subjects with a history of chronic or recurrent infections (more than 3 episodes requiring 
antibiotics or antivirals during the preceding year), recent serious or life-threatening infection 
within the 6 months prior to the Baseline Visit (including hospitalization for any infection in 
the last 6 months or any current sign or symptom that may indicate an infection).
15. Subjects with a history of herpes zoster infection within 6 months prior to the Baseline Visit.
16. Subjects with known TB infection, at high risk of acquiring TB infection, or LTB infection 
are excluded.
a.
Known TB infection whether present or past is defined as:

Active TB infection or clinical signs and symptoms suggestive of TB 
(pulmonary or extra pulmonary)

History of active TB infection involving any organ system or findings in other 
organ systems consistent with TB infection 

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:

Known exposure to another person with active TB infection within the 3 months 
prior to Screening

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.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 46 of 173
c.
Latent TB infection (unless appropriate prophylaxis is initiated prior to study treatment 
and continued to completion of prophylaxis). Please refer to Section 12.7.3 for further 
details and instructions.
17. Subjects with current acute or chronic viral hepatitis B or C or with human 
immunodeficiency virus (HIV) infection.
18. Subjects with current or a history of active infection with histoplasma, coccidiodes, 
paracoccidioides, pneumocystis, nontuberculous mycobacteria, blastomyces, or aspergillus.
19. Subjects must not have had a history of an infected joint prosthesis any time.
20. Subjects receiving any live (includes attenuated) vaccination within the 8 weeks prior to 
Baseline (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal 
influenza vaccination is not allowed).
21. Subjects who, in the Investigator's opinion, have a high risk of infection (eg, subjects with 
leg ulcers, indwelling urinary catheter, persistent or recurrent chest infections, and subjects 
who are permanently bedridden or wheelchair bound).
22. Subjects with a history of a lymphoproliferative disorder including lymphoma or current 
signs and symptoms suggestive of lymphoproliferative disease.
23. Current malignancy or a history of malignancy, although subjects with less than 3 completely 
excised basal cell carcinomas or with cervical carcinoma in situ successfully surgically 
treated more than 5 years prior to Screening may be included.
24. Subjects with Class III or IV congestive heart failure as per the New York Heart Association 
(NYHA) 1964 criteria.
25. Subjects with a history of or suspected demyelinating disease of the central nervous system 
(eg, multiple sclerosis or optic neuritis).
26. Subjects who have had major surgery (including joint surgery) within 8 weeks prior to 
Screening or have planned surgery within 6 months of the Screening Visit.
27. Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, 
hematological, endocrine, pulmonary, cardiac, or neurological disease, as determined by the 
Investigator. 
28. Subjects with significant laboratory abnormalities included but not limited to: 

Liver function tests >2.0 x ULN

Estimated Glomerular Filtration Rate (GFR) as measured by Chronic Kidney Disease 
Epidemiology Collaboration (Levey et al, 2009) <60 mL/min/1.73m2

White blood cell (WBC) <3.0x109/L
29. Subjects with any other condition that, in the Investigator’s judgment, would make the 
subject unsuitable for inclusion in the study.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 47 of 173
6.3
Withdrawal and escape criteria
6.3.1
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 takes prohibited concomitant medications as defined in this protocol.
4. Subject withdraws his/her consent.
5. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test.
6. The Sponsor or a regulatory agency requests withdrawal of the subject.
7. Subject’s subsequent TB test was confirmed positive or any further evidence is suggestive of 
potential TB infection (eg, exposure) and further examinations result in a diagnosis of active 
TB, or in case of LTB no prophylactic treatment was initiated. Refer to Section 12.7.3 for 
further details and instructions.
Once withdrawn from study treatment, subjects must return for the WD Visit, complete all WD 
assessments, and complete a final SFU Visit 10 weeks after the last dose of study medication.
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 Case Report form must document the primary reason for withdrawal or 
discontinuation.
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a subject in advance.
Subjects withdrawn from the study will not be replaced.
6.3.2
Escape treatment
Subjects receiving placebo or half-dose CZP (200mg Q4W) who experience a flare during the 
Double-Blind Period will escape to full-dose treatment (CZP 200mg Q2W) until the end of that 
period or for at least 12 weeks, whichever is longer. The escapers need to come back to the site 
at the timepoint of the escape (Week 0), 2 and 4 weeks after escape (Weeks 2 and 4), and every 
12 weeks thereafter until the originally scheduled Week 96.
Subjects escaping from placebo to full-dose CZP (200mg Q2W) will receive a loading dose of 
CZP (400mg Q2W; 2 injections) at the 3 consecutive visits after the flare. Subjects escaping 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 48 of 173
from half-dose CZP to full-dose CZP will receive a loading dose of CZP 200mg Q2W at the 3 
consecutive visits after the flare. In order to maintain the blind, subjects escaping from half-dose 
CZP to full-dose CZP will receive a placebo administration and a CZP 200mg administration (a 
total of 2 injections) at these 3 visits (Figure 7.1). 
Subjects randomized to the CZP full-dose (200mg Q2W) treatment during the Double-Blind 
Period who qualify for escape will remain on their current treatment allocation. As with subjects 
escaping from half-dose CZP to full-dose CZP, these subjects will receive a placebo and 
CZP 200mg injection (a total of 2 injections) at the 3 visits after the flare in order to maintain the 
blind to the randomized treatment. 
After the loading dose (200mg Q2W or 400mg Q2W), all escaped subjects will continue full-
dose CZP treatment in an open-label fashion.
The definition of flare is provided in Section 3.
At the Investigator’s discretion, the subject may be withdrawn from the study at any time (eg, to 
receive alternative treatment for the disease).
7
STUDY TREATMENT(S)
7.1
Description of investigational medicinal product(s)
Investigational medicinal products will be supplied under the responsibility of the UCB Clinical 
Supply Unit. The frequency at which the IMP will be supplied to each individual center will be 
adapted to the recruitment capacity of that center and to the expiry date of the IMP and will be 
managed by the IXRS.
Drug supplies will consist of the following:
Certolizumab pegol is supplied as a sterile, clear, and colorless to slightly yellow liquid solution 
with a pH of approximately 4.7 in 1mL single use glass prefilled syringe (PFS) with a 
25G ½ inch thin wall needle for sc administration. Each syringe contains an extractable volume 
of 1mL at a concentration of 200mg/mL of CZP in 10mM sodium acetate buffer and 125mM 
sodium chloride as a tonicity agent.
Placebo is supplied in a PFS with a 25G ½ inch thin-wall needle, containing an injectable 
volume of 1mL 0.9% saline for single use.
Due to the difference in presentation and viscosity between CZP and placebo, special precautions 
will be taken in order to ensure maintained blinding of the study (unblinded/blinded site 
personnel and monitors).
7.2
Treatment(s) to be administered
Treatments to be administered are as described in Section 5.1.
7.2.1
Treatment administration
Part A
A Pharmacy Manual will be provided to each site containing instructions regarding drug 
preparation and dosing. The administration schedule is described in Section 5.1.1.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 49 of 173
Study medication will be given sc by dedicated and adequately trained site personnel or the 
subject may start self-administering from Week 6 after training at Week 2 and Week 4.
Suitable areas for administrations are the lateral abdominal wall and upper outer thigh. During 
each dosing visit, if 2 injections are being administered (ie, loading dose CZP 400mg as 
2 injections of 200mg each) each of the 2 injections should be administered at a separate 
injection site.
Study medication should be administered with a minimum of 10 days between the 
CZP 200mg Q2W administrations. Each deviation less than the minimum timeframe must be 
discussed immediately with the Medical Monitor for safety purposes.
Part B
A Pharmacy Manual will be provided to each site containing instructions regarding drug 
preparation and dosing. The administration schedule is described in Section 5.1.2.
Injections will be given sc by dedicated, unblinded and adequately trained site personnel. 
Suitable areas for administrations are the lateral abdominal wall and upper outer thigh. 
Injections should be administered with a minimum of 10 days between the CZP 200mg Q2W 
administrations. Each deviation less than the minimum timeframe must be discussed 
immediately with the Medical Monitor for safety purposes.
7.3
Packaging
For Part A and B, CZP and placebo are packaged and labeled according to Good Manufacturing 
Practice guidelines and applicable laws or regulations. They are suitably packaged in such a way 
as to protect the IMP from deterioration during transport and storage.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Conference on 
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good Manufacturing 
Practice and will include any locally required statements. If necessary, labels will be adapted to 
the size of IMP package, and translated into the local language. Details on the labeling of the 
IMP will be provided in the Pharmacy Manual.
7.5
Handling and storage requirements
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
The IMP stored by the Investigator is to be kept in a secured area with limited access. The IMP 
containers should be stored at 2 to 8°C and protected from light. 
Appropriate storage conditions must be ensured by a controlled temperature and by completing a 
temperature log in accordance with local requirements on a regular basis (eg, once a week) 
showing minimum and maximum temperatures reached over the recorded time interval.
In case an out of range temperature is noted, it must be immediately communicated to the 
Sponsor’s designee in accordance with the Pharmacy Manual.
The Investigator (or designee) will instruct the subject to store the IMP following the instructions 
on the label.
Detailed information on handling and storage of IMP will be given in the Pharmacy Manual.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 50 of 173
7.6
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP lost (due to breakage or wastage), not used, disposed of at the study site, or returned to 
the Sponsor or designee must also be recorded on the appropriate forms. All supplies and 
pharmacy documentation must be made available throughout the study for UCB (or designee) to 
review.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of 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 Investigator must ensure that the IMP is used only in accordance with the protocol.
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers) and unused IMP containers must be reconciled and returned to UCB (or designee), 
preferably in their original package. Investigational medicinal product intended for the study 
cannot be used for any other purpose than that described in this protocol.
All study medication documentation (eg, shipping receipts, drug accountability logs, IXRS 
randomization materials) must be maintained and accessed by unblinded, trained site personnel 
only. Designated, unblinded site personnel must be appropriately trained and licensed (per 
country guidelines) to administer study drug. Each site will be required to have a written blinding 
plan in place signed by the Principal Investigator, which will detail the site’s steps for ensuring 
that the double blind nature of the study is maintained from Week 48 to Week 96. 
7.7
Procedures for monitoring subject compliance
At each visit after IMP is dispensed, subjects must return all unused IMP and empty IMP 
containers. Drug accountability must be done in the subject’s presence in order to obtain 
explanations regarding discrepancies in compliance with the dosing regimen. Drug 
accountability must be recorded on the Drug Accountability form.
Part A (Open-Label Period: Week 0 [Baseline] to Week 48)
If a subject is found to be persistently noncompliant (3 or more missed doses in total over 
48 weeks), the Sponsor, in conjunction with the Investigator, will make a decision as to whether 
the subject should be withdrawn from the study. Doses of IMP that were missed due to a 
reasonable interfering AE that does not allow administration of an anti-TNF due to safety 
reasons, will not be considered for the evaluation of subject compliance. Evaluation of the 
reasonability of the AE must be discussed immediately with the Medical Monitor.
Part B (Double-Blind Period: Week 48 to Week 96)
If a subject is found to be persistently noncompliant (3 or more missed doses over any period of 
48 weeks), the Sponsor, in conjunction with the Investigator, will make a decision as to whether 
the subject should be withdrawn from the study. Doses of IMP that were missed due to a 
reasonable interfering AE that does not allow administration of an anti-TNF due to safety 
reasons, will not be considered for the evaluation of subject compliance. Evaluation of the 
reasonability of the AE must be discussed immediately with the Medical Monitor.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 51 of 173
7.8
Concomitant medication(s)/treatment(s)
For any subject taking any medication, including over the counter products, nutraceutical 
products, or herbal medications at Screening or at any time during the course of the study, an 
accurate record must be kept in the clinic chart (source documentation) and the eCRF. This 
record should include the name of the drug, the dose, the date(s) of administration, and the 
indication for use.
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications/treatments are permitted during the study, from Baseline 
onward, with restrictions as specified:

NSAIDs/cyclooxygenase 2 (COX-2) inhibitors: doses should be stable throughout the study 
and ad hoc as needed (prn) inhibitors should not be used 24 hours prior to any post-Screening 
study visit. No change in dose or dose regimen is allowed during the study except for reasons 
of safety, where the NSAIDs/COX-2 inhibitors dose may be decreased or discontinued.
NSAID dose may be down-titrated at Investigator discretion. The reduction in NSAID dose if 
clinically indicated is permitted at the discretion of the Investigator until Week 28, however 
after that timepoint the NSAID treatment should remain stable as much as possible.

Stable doses of analgesics (including, but not limited to acetaminophen, paracetamol, 
NSAIDs, opiates or combinations) will be permitted except that ad hoc (prn) usage is 
prohibited within the 14 days prior to Baseline or 24 hours prior to any post-Screening 
assessments. 

Corticosteroids (see Section 7.8.2 for prohibited corticosteroids):

Oral chronic stable doses are allowed as long as the maximum daily total prednisone 
equivalent dose is ≤10mg. Oral corticosteroid tapers of less than 14 days used to treat 
other indications (asthma exacerbation, contact dermatitis, etc.) are allowed as long the 
maximum daily dose is ≤20mg. The taper must end 1 week before a study visit.

Intra-articular (ia): ia administrations of corticosteroids are permissible in peripheral 
joints; however, after an ia injection the joint will no longer be evaluated for data 
regarding swollen and tender joints.

Intravenous (iv): iv administration of corticosteroid will be permitted for the purposes of 
stress dosing for a surgical procedure under general or spinal anesthesia. Furthermore, iv 
administration of corticosteroids may be used during the study for acute illnesses as long 
as the dose is not given within 1 week prior to Week 12, Week 24, Week 48, or Week 96, 
and the underlying disease does not present a contraindication to the subject remaining in 
the study. Indications might include dermatitis, gastroenteritis, asthma exacerbation, and 
pneumonia.

Slow-acting anti-rheumatic drugs (SAARDs) (only SSZ and/or HCQ and/or MTX and/or 
azathioprine [AZA] and/or leflunomide [LFN]: maximum SSZ ≤3g daily; HCQ ≤400mg 
daily; MTX ≤25mg weekly; AZA ≤150mg daily; LFN ≤20mg daily) are allowed. No change 
in dose or dose regimen is allowed during the study except for reasons of intolerance, where 
the SAARDs dose may be reduced or discontinued. No change is permitted in the route of 
administration for MTX (sc, or oral) during the study.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 52 of 173

Osteoporosis medications (eg, risedronate, alendronate, ibandronate, denosumab, cathepsin K 
inhibitor, cinacalcet, calcitonin) with the exception of iv bisphosphonates are allowed 
without restriction.
7.8.2
Prohibited concomitant treatments (medications and therapies)
Prior medication exclusions and washout periods are listed in Section 6.2. In addition, use of the 
following concomitant medications is prohibited during the study, except where indicated:

Corticosteroids (administered oral, iv/ia) are permitted only as described in Section 7.8.1. 
Intramuscular corticosteroids and SIJ ia corticosteroid injections are not permitted. 

Hyaluronic acid may be used as ia injection in the knee only.

Specific SAARDs (cyclosporine, cyclophosphamide, mycophenolic acid, apremilast).

Biologicals (TNF antagonists: IFX, ADA, ETN, GOL; abatacept [ABA]; CZP; Rituximab or 
other anti-CD20 antibodies; tocilizumab; ustekimumab; tofacitinib; also any other biological 
response modifiers which are not licensed for the treatment of AS or axSpA).

All iv bisphosphonates (zoledronic acid, ibandronate, pamidronate) are excluded.
Subjects must not participate in any other clinical study for any indication or receive any 
unauthorized medication during the Study Period.
If the subject requires any of the medications specified in this section, the subject must be 
withdrawn from the study prior to the initiation of these medications.
The administration of live vaccines is not recommended for subjects treated with TNF 
antagonists. Live vaccines should not be administered 8 weeks prior to Baseline. If immunization 
with a live organism-based vaccine is considered during the study, the clinician is urged to 
carefully weigh the risks vs benefits of immunization. If the subject is going to proceed with live 
organism-based immunization, the subject must be withdrawn from the study prior to 
administration of the vaccine. Such vaccines must be recorded in the eCRF.
7.8.3
Rescue medication
Escape treatment is as described in Section 5.1.3.
7.9
Blinding
Due to differences in presentation and viscosity between active and placebo, special precautions 
will be taken in order to ensure blinding of the study during Part B. The subject will receive the 
IMP throughout the study duration for each single administration in a sealed box with a PFS 
containing either CZP 200mg or placebo. Packaging and labeling will be done in a way to ensure 
that the provided box including the PFS will not provide any information about the assigned 
treatment of the study (CZP 200mg or placebo). Administration of the IMP will be done 
according to the schedule of study assessments (Table 5.1) either onsite by appropriately trained 
unblinded study personnel or at home by the unblinded home nurse. 
The injection schedule can be seen in Figure 7.1.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 53 of 173
Figure 7.1:
Injection Schedule
CZP=certolizumab pegol; PBO=placebo; Q2W=every 2 weeks; Q4W=every 4 weeks; W=Week
0
2
4
6
8
10
12
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16
18
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22
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PART A - Open-label Period
●
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example: 200 mg CZP Q2W escaping to 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 54 of 173
7.9.1
Procedures for maintaining and breaking the treatment blind
7.9.1.1
Maintenance of study treatment blind
All subject treatment details will be allocated and maintained by the IXRS.
Part B of the study will be double blind and placebo controlled for 48 weeks. No study team 
member involved in the clinical conduct will have access to the randomization schedule until 
after database lock and unblinding. 
7.9.1.2
Breaking the treatment blind in an emergency situation
All Sponsor, Investigator site, and Contract Research Organization (CRO) staff involved with the 
study will be blinded to the treatment code until the database lock (ie, after completion of the 
Double-Blind Period) with the following exceptions:

Sponsor clinical study supplies coordinator, packager, and qualified person

Pharmacy monitors who monitor unblinded pharmacy documentation

Sponsor pharmacovigilance staff reporting serious adverse events (SAEs) to regulatory 
authorities

Emergency service provider staff at the 24/7 SAE reporting hotline

Laboratory staff analyzing blood samples for CZP plasma concentrations and ADAb

Site study medication administrator
The appropriate persons (Investigators, Single Safety Case Management (SSCM) - Safety 
Officer, Medical Monitor) will be provided with an individual password to access the IXRS 
menu that will enable them to unblind a subject's double-blind treatment allocation. This 
password must be kept confidential and not shared with any other persons. The IXRS will be 
able to identify the individual who has unblinded a subject's treatment allocation. The IXRS will 
be accessible at all times. If possible, Investigators are advised to contact the company or its 
representatives prior to unblinding the treatment allocation of subjects. 
Under normal circumstances, the blinded treatment must not be revealed. In the case of a 
medical emergency, UCB or its representatives preferably should be contacted prior to any 
unblinding. The blind should be broken only if doing so will change the decision making as to 
the subject's treatment or clinical intervention. Any unblinding performed by the Investigator of 
the IMP must be documented and explained by the Investigator. If the blind is broken, the date, 
the reason for the breaking the blind, and person doing so must be recorded. UCB or its 
representatives must be notified immediately if the blind is broken.
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the subject has been allocated by contacting the IXRS. All sites will be provided with details of 
how to contact the system for code breaking at the start of the study. The Medical Monitor or 
equivalent should be consulted prior to unblinding, whenever possible.
For the product and study information and emergency unblinding purposes, the Sponsor will 
provide each Investigator with an appropriate quantity of clinical study subject cards. Each 
subject will be instructed to keep the card with him/her at all times. These subject cards will be 
written in the language of the subject. The Investigator will fill in each card with the details of 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 55 of 173
his/her contact information (eg, Investigator stamp) and subject identifier. The card will be 
distributed to the subject at the time of informed consent.
The Clinical Project Manager (CPM) or designee will be informed immediately via the IXRS 
when a code is broken, but will remain blinded to specific treatment information. Any unblinding 
of the IMP performed by the Investigator must be recorded in the source documents and on the 
Study Termination eCRF page.
7.10
Randomization and numbering of subjects
An IXRS will be used for assigning eligible subjects to a treatment regimen based on a 
predetermined production randomization and/or packaging schedule provided by the CRO. The 
IXRS will generate individual assignments for subject kits of IMP, as appropriate, according to 
the visit schedule.
To enroll a subject (Screening), the Investigator or designee will contact the IXRS and provide 
brief details about the subject to be enrolled. Each subject will receive a 5-digit number assigned 
at screening that serves as the subject identifier throughout the study. The subject number will be 
required in all communication between the Investigator or designee and the IXRS regarding a 
particular subject. Subject numbers and kit numbers will be tracked via the IXRS.
The stratification for mNY classification will have the following 2 levels:

mNY-positive

mNY-negative
For enrollment in Part A, the IXRS will be designed to ensure that at least 45% and no more than 
55% of the subjects belong to each of the 2 clinical subgroups above. Throughout the study, 
IXRS will be used for the calculation of ASDAS.
To randomize a subject (Week 48), the Investigator or designee will contact the IXRS and 
provide brief details about the subject to be randomized. The IXRS will automatically inform the 
Investigator or designee of the subject’s randomization number. The IXRS will allocate kit 
numbers to the subject based on the subject number during the course of the study.
Randomization will be stratified on:

Geographic region (North America, Western Europe, Eastern Europe, and Asia)

mNY classification
In order to eventually end up with 210 subjects in sustained clinical remission qualifying for 
Part B, the enrollment will be adjusted accordingly. For such, the ASDAS will be monitored 
during Part A at various timepoints to predict the expected percentage of enrolled subjects 
responding well to the treatment and likely to achieve sustained remission at the end of Part A. 
Subjects will be allocated to treatment during Part B in a 1:1:1 ratio (CZP 200mg Q2W: 
CZP 200mg Q4W: placebo). 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 56 of 173
8
STUDY PROCEDURES BY VISIT 
Section 5.2 (Schedule of assessments) provides a general overview of study assessments. A 
detailed listing of procedures to be undertaken at each visit is described below. 
During the study, the Investigator will assess each subject over the entire study period of up to 
109 weeks including a SFU Period of 10 weeks after the last dose. Visit windows of ±3 days on 
either side of the scheduled dosing are permitted; however, the Investigator should try to keep 
the subjects on the original dosing schedule. The window of ±3 days is relative to Baseline and 
applicable for all subsequent visits. Changes to the dosing schedule outside of the 3-day window 
must be discussed with the Medical Monitor and may result in subject withdrawal. For the 
conduct of MRI, the acceptable time window is ±2 weeks.
8.1
Screening Visit (up to 5 weeks)
Prior to any study activities, subjects will be asked to read and sign an informed consent form for 
participation in the study AS0005 and - optional - for obtaining pharmacogenomic samples. All 
informed consent forms have been approved by an IEC/IRB and the Sponsor and comply with 
regulatory requirements. Subjects will be given adequate time to consider any information 
concerning the study given 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. 
Assessments at the Screening Visit include:

Review inclusion/exclusion criteria

Confirm informed consent

Demographic data (includes date of birth, gender, race/ethnicity)

Washout of prohibited medications

Significant past medical and procedure history and concomitant disease (includes allergy and 
any current symptoms); axSpA history; history of extra-articular manifestations (including 
number of extraarticular episodes during the previous 12 months for psoriasis and IBD and 
24 months for uveitis before Screening)

Vital signs (pulse rate, systolic and diastolic blood pressures, temperature and respiratory 
rates)

Hematology, biochemistry, and urine for clinical laboratory values (includes a serum 
pregnancy test for women of childbearing potential, HLA-B27 and testing to rule out 
hepatitis B surface antigen, antibodies to hepatitis C, antibodies to HIV, and CRP) 

Physical examination (including weight, evaluation of signs and symptoms of active TB and 
risk factors for exposure to TB)

Screening chest x-ray must have occurred within 3 months prior to Screening

TB test: IGRA test (QuantiFERON TB GOLD test [or another WHO-validated IGRA test 
such as Elispot test only when QuantiFERON test indicated but not available]). 

TB evaluation questionnaire 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 57 of 173

Sacroiliac joint x-ray (centrally read). An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit maybe used as the Baseline assessment provided that the film can be 
submitted and meets the requirements for central reading.

MRI (centrally read)

BASMI and Spinal mobility assessments

BASDAI

PtGADA

Prior medications

Fecal sample kit provided to the subject

Contact the IXRS to indicate the subject has been screened
The period between the Screening and Baseline Visits must not exceed 5 weeks. The Screening 
chest x-ray should be read by a radiologist or pulmonologist and must exclude evidence of TB. 
The qualifying CRP levels from the Screening Visit will be used for the Inclusion Criteria review 
at Baseline. One retesting of CRP is permitted during the Screening Period in order to meet the 
Inclusion Criteria.
Subjects who initiate treatment for LTB infection during the Screening Period must repeat initial 
screening laboratory parameters, all examinations, and questionnaires (after receiving at least 4 
weeks of treatment for LTB infection) prior to randomization in the study, and must plan to 
continue the full course of therapy. It is recommended that the QuantiFERON TB GOLD test be 
the first test performed at Screening to reduce the number of screening procedures conducted for 
any QuantiFERON positive subjects that may need to be treated for TB prophylaxis or 
potentially withdrawn from the study. The Investigator must assess that the subject’s likelihood 
of completing the therapy is high and duly record their opinion in the subject’s record prior to 
randomizing the subject. 
8.2
Baseline Visit (Week 0)
Subjects qualifying for this study will have the following procedures performed/recorded prior to 
study medication administration:

Review of inclusion/exclusion criteria (The qualifying CRP levels from the Screening Period 
will be used for the inclusion criteria review at Baseline.)

Vital signs (pulse rate, systolic and diastolic blood pressures, temperature and respiration 
rates)

Blood samples will be collected for hematology, biochemistry analyses, serum calprotectin,
and CRP 

Urine will be collected for urinalysis and for a urine pregnancy test for women of 
childbearing potential

Physical examination (including extra-articular assessments, height, and weight)

TB questionnaire
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 58 of 173

BASMI and spinal mobility 

BASDAI 

BASFI 

SF-36 

ASQoL 

EQ-5D 

MASES

Total spinal pain NRS and nocturnal spinal pain NRS 

Swollen and tender joint counts

PtGADA

PhGADA

WPS

Resources utilization

IBD-Q 

Plasma sample for CZP concentration, ADAb

Plasma sample for biomarkers, if applicable

Genetics/epigenetics, proteomics if applicable

Stool sample provided by the subject for fecal calprotectin evaluation

Prior medications

AEs

Contact IXRS to randomize subject and to obtain kit number 

Study drug administration (after all other visit assessments are completed and laboratory 
samples are drawn)
8.3
Weeks 2 to 96/WD onsite visits
8.3.1
Weeks 2, 4, 12, 24, 32, 36, 48, 52, 60, 72, 84, and 96/WD (± 3 Days)
Assessments at these onsite visits include:

Vital signs: pulse rate, systolic and diastolic blood pressures, temperature will be measured 
(all visits). If a subject experiences an AE, respiration rate will be measured in addition. 

Blood samples will be collected for hematology and biochemistry analyses (at Weeks 12, 24, 
32, 36, 60, 72, 84, and at Week 96/WD), and CRP (at Weeks 2, 4, 12, 24, 32, 36, and from 
Week 52 onwards every 4 weeks only).

Urine pregnancy testing for women of childbearing potential will be at Week 96/WD only.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 59 of 173

Urine will be collected for urinalysis (at Weeks 12, 24, 32, 36, 48, 60, 72, 84, and at 
Week 96/WD). 

Physical examination (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD), including 
weight at Week 48 and at Week 96/WD.

Extra-articular assessments (at Weeks 4, 12, 24, 36, 48, 52, 60, 72, 84, and at Week 96/WD).

TB test (at Week 48 and at Week 96/WD only).

TB questionnaire (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD).

MRI (at Week 48 and at Week 96/WD only). 

BASMI and spinal mobility (at Weeks 2, 4, 12, 24, 36, 48, 52, 60, 72, 84, and at 
Week 96/WD only).

BASDAI (at Weeks 2, 4, 12, 24, 32, 36, 52, 60, 72, 84, and at Week 96/WD).

BASFI (at Weeks 2, 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

SF-36 (at Weeks 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

ASQoL (at Weeks 2, 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

EQ-5D (at Weeks 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

IBD-Q (at Week 96/WD only).

MASES (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Total spinal pain NRS and nocturnal spinal pain NRS (at Weeks 2, 4, 12, 24, 36, 52, 60, 72, 
84, and at Week 96/WD only).

Swollen and tender joint counts (at Weeks 2, 4, 12, 24, 36, 48, 52, 60, 72, 84, and at 
Completion at Week 96/WD only).

PtGADA (at Weeks 2, 4, 12, 24, 32, 36, and from Week 52 onwards every 4 weeks only).

PhGADA (at Weeks 12, 24, 36, 48, 52, 60, 72, 84, and at Week 96/WD only).

WPS (at Weeks 4, 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Resource utilization (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Plasma for CZP concentration and ADAb (at Weeks 4, 12, 24, 60, 72, 84, and at 
Week 96/WD only).

Plasma for biomarkers (at Weeks 4, 12, 24, 60, 72, 84, and at Week 96/WD only), if 
applicable.

Genomics and proteomics (at Weeks 12, 24, 72, and at Week 96/WD only), if applicable.

Stool sample will be collected for fecal calprotectin at Week 48 and at Week 96/WD only.

Blood sample will be collected for serum calprotectin at Week 12, Week 24, Week 72 and 
Week 96/WD only.

Concomitant medication
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 60 of 173

AEs

Contact IXRS to obtain next kit numbers.

Study drug administration (after all other visit assessments are completed and laboratory 
samples are drawn) (all visits except at Week 96/WD).

Randomization at Week 48

Check of sustained remission criteria (all visits except Weeks 2, 4, and Week 96/WD visit).
8.3.2
3 to 5 days prior to Week 48

Blood samples will be collected for hematology and biochemistry analyses and CRP

BASDAI

BASFI 

SF-36 

ASQoL 

EQ-5D 

IBD-Q 

Total spinal pain NRS and nocturnal spinal pain NRS

PtGADA

Plasma for CZP concentration and ADAb

Plasma for biomarkers 

Genetics

Blood sample will be collected for serum calprotectin

AEs
8.4
Weeks 6 to 94 home visits and home nurse visits
8.4.1
Home visits during Part A
Assessments at these home visits include:

Study drug self-administration at home (at Weeks 6, 8, 10, 14, 16, 18, 20, 22, 26, 28, 30, 34, 
38, 40, 42, 44, and 46)

Subjects will be contacted by telephone in between the onsite visits (at Weeks 6 to 10, 14 to 
22, 26 to 30, and 38 to 46)
8.4.2
Home and home nurse visits during Part B
Assessments at these home and nurse visits include:

Vital signs: pulse rate, systolic and diastolic blood pressures, temperature will be measured. 
If a subject experiences an AE, respiration rate will be measured in addition (at Week 50, 
Weeks 54 to 58, 62 to 70, 74 to 82, and 86 to 94 only)
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8.4

UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 61 of 173

CRP and PtGADA (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)

BASDAI (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)

Contact IXRS to report kit number (all Visit at Weeks 50, 54 to 58, 62 to 70, 74 to 82, and 86 
to 94) 

Nurse visit at subject home including to perform study medication administration (at Weeks 
50, 54, 56, 58, 62, 64, 66, 68, 70, 74, 76, 78, 80, 82, 86, 88, 90, 92, and 94)

Check of sustained remission criteria (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)
8.5
Study procedures after flare until the final assessment visit at 
Week 96/WD
The assessment schedule for subjects experiencing a flare in Part B will start 2 weeks after the 
flare condition is fulfilled (Escape Week 0) and will end 2 weeks before the final assessment 
visit at Week 96 (whereas the appointment for Week 96 is to be scheduled in accordance to the 
regular assessment schedule [Table 5.1] with Week 0 as Baseline). If the flare occurs late in 
Part B (at or after Week 82), the subject must receive the escape treatment for 12 weeks (eg, 
starting at Week 84 [Escape Week 0] until Week 96 [Escape Week 12]). The final assessments at 
study end (as laid down for Week 96 of the regular schedule) must be performed 2 weeks after 
the last study dose administration accordingly (ie, 98 weeks after Baseline for the example 
provided).
Assessments and their timing after a flare are specified in Table 5.2 and include:

Vital signs: pulse rate, systolic and diastolic blood pressures, temperature will be measured at 
Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final assessment visit at 
Week 96/WD. If a subject experiences an AE, respiration rate will be measured in addition

Blood samples will be collected for hematology and biochemistry analyses at Escape Week 0 
and every 12 weeks thereafter until the final assessment visit at Week 96/WD

Urine will be collected for urinalysis at Escape Week 0 and every 12 weeks thereafter until 
the final assessment visit at Week 96/WD

CRP at Escape Weeks 0, 2, 4, and every 4 weeks thereafter until the final assessment visit at 
Week 96/WD

MRI at Escape Weeks 0 and 12, and at final assessment visit at Week 96/WD, if the last MRI 
was done at least 12 weeks prior to Week 96/WD

Stool sample will be collected for fecal calprotectin and blood sample for serum calprotectin 
at Escape Weeks 0 and 12

IBD-Q at Escape Weeks 0 and 12

Physical examination at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the 
final assessment visit at Week 96/WD

Extra-articular assessments at Escape Weeks 0, 4, 12, and every 12 weeks thereafter until the 
final assessment visit at Week 96/WD
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 62 of 173

TB questionnaire at Escape Week 0 and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD

BASMI and spinal mobility at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until 
the final assessment visit at Week 96/WD

BASDAI at Escape Weeks 0, 2, 4, and every 4 weeks thereafter until the final assessment 
visit at Week 96/WD

BASFI at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD

SF-36 at Escape Weeks 0, 4, 12, and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD

ASQoL at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD

EQ-5D at Escape Weeks 0, 4, 12, and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD

MASES at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final assessment 
visit at Week 96/WD.

Total spinal pain NRS and nocturnal spinal pain NRS at Escape Weeks 0, 2, 4, 12, and every 
12 weeks thereafter until the final assessment visit at Week 96/WD

PtGADA at Escape Weeks 0, 2, 4, and every 4 weeks thereafter until the final assessment 
visit at Week 96/WD

PhGADA at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final 
assessment visit at Week 96/WD

WPS at Escape Weeks 0, 4, 12, and every 12 weeks thereafter until the final assessment visit 
at Week 96/WD

Resource utilization at Escape Weeks 0, 4, 12, and every 12 weeks thereafter until the final 
assessment visit at Week 96/WD

Plasma for CZP concentration and ADAb at Escape Weeks 0, 2, 4, 12, and every 12 weeks 
thereafter until the final assessment visit at Week 96/WD

Plasma for biomarkers at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the 
final assessment visit at Week 96/WD, if applicable.

Concomitant medication at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the 
final assessment visit at Week 96/WD

AEs

Contact IXRS to obtain next kit numbers

Study drug administration (after all other visit assessments are completed and laboratory 
samples are drawn) at site and study drug self-injection at home
Refer to Table 5.1 and Section 8.3 for the final assessments due at Week 96/WD.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 63 of 173
8.6
Safety Follow-Up Visit
Assessments at this visit include:

Vital signs; pulse rate, systolic and diastolic blood pressures, and temperature (respiration 
rate will be assessed in addition if the subject experiences an AE)

Blood samples will be collected for hematology, biochemistry analyses, and pregnancy test

Urine will be collected for urinalysis

Physical examination 

Plasma for CZP concentration and ADAb

Plasma for biomarkers 

Concomitant medication

AEs

Contact IXRS to indicate that subject has completed the SFU
8.7
Withdrawal Visit
Assessments to be conducted at the WD Visit are specified in Section 8.3 for Week 96/WD.
8.8
Unscheduled Visit
It is at the Investigator's discretion to initiate an Unscheduled Visit, if deemed necessary by the 
Investigator for the subject's safety and well-being. At this visit, any of the following 
assessments may be performed dependent on the presenting reason:

Vital signs 

Blood samples for hematology, biochemistry analyses, other testing such as for TB or CRP

Urine for urinalysis and/or pregnancy testing (for women of childbearing potential)

Physical examination

Concomitant medication

AEs

TB questionnaire
9
ASSESSMENT OF EFFICACY
Most of these tools have been used in AS studies but data support their use also in axSpA studies 
(Haibel et al, 2008; Barkham et al, 2009).
9.1
Assessment of primary and secondary efficacy variables
9.1.1
ASAS20, ASAS40, ASAS 5/6 response, and ASAS partial remission
The ASAS20 is defined as an improvement of at least 20% and absolute improvement of at least 
1 unit on a 0 to 10 NRS in at least 3 of the 4 following domains:

Patient's Global Assessment of Disease Activity (see Section 9.2.3)
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9.1

UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 64 of 173

Pain assessment (the total spinal pain NRS score)

Function (represented by BASFI, Section 9.1.3)

Inflammation (the mean of the BASDAI questions 5 and 6, [see Section 9.1.2] concerning 
morning stiffness intensity and duration) 
and absence of deterioration in the potential remaining domain (deterioration is defined as a 
relative worsening of at least 20% and an absolute worsening of at least 1 unit).
The ASAS criteria for 40% improvement are defined as relative improvements of at least 40%, 
and absolute improvement of at least 2 units on a 0 to 10 NRS in at least 3 of the 4 domains and 
no worsening at all in the remaining domain.
The ASAS 5/6 response is defined as at least 20% improvement in 5 of 6 domains, including 
spinal mobility (lateral spinal flexion) and CRP as more objective measures (Brandt et al, 2004).
The ASAS PR response is defined as a score of ≤2 units on a 0 to 10 unit scale in all 4 domains 
listed above for ASAS20.
The ASAS variables will be calculated at Weeks 0, 2, 4, 12, 24, 36, 48, 52, 60, 72, 84, and 96.
The ASAS assessments per visit are described in the schedule of study assessments Table 5.1. 
9.1.2
Bath ankylosing spondylitis disease activity index (BASDAI)
The most common instrument used to measure the disease activity of AS from the subject’s 
perspective and in the broad AxSpA population is the BASDAI (van Tubergen et al, in press 
2015; Garrett et al, 1994). The BASDAI is a validated self-reported instrument which consists of 
six 10-unit horizontal NRSs to measure severity of fatigue, spinal and peripheral joint pain and 
swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last 
week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease 
activity. The minimal clinically important difference (MCID) used to interpret scores is 10mm 
on a VAS or 22.5% of the Baseline score (Pavy et al, 2005). An MCID of 1 unit will be selected 
for the NRS version. 
The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI response.
The BASDAI is calculated as follows: 
Fatigue item of the BASDAI
Fatigue as a major symptom of AS can effectively be measured with single item questions such 
as the BASDAI item (van Tubergen et al, 2002b). This item has shown moderate to good 
reliability and responsiveness (van Tubergen et al, 2002b). The same MCID will be used for the 
fatigue item of the BASDAI as for the total BASDAI score, ie, a change of 1 unit on the NRS.
The BASDAI assessments per visit are described in the schedule of study assessments Table 5.1.
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9.1.3
Bath ankylosing spondylitis functional index (BASFI)
The BASFI is a validated disease-specific instrument for assessing physical function (van 
Tubergen et al, in press 2015; Calin et al, 1994, van der Heijde et al, 2005). The BASFI 
comprises 10 items relating to the past week. The NRS version will be used for the answering 
options of each item on a scale of 0 (“Easy”) to 10 (“Impossible”) (van Tubergen et al, 2002a). 
The BASFI is the mean of the 10 scores such that the total score ranges from 0 to10, with lower 
scores indicating better physical function. The MCID used to interpret scores is 7mm on a 0 to 
100mm VAS or 17.5% of the Baseline score (Pavy et al, 2005); an MCID of 1 unit will be used 
for the NRS version.
The BASFI assessments per visit are described in the schedule of study assessments Table 5.1.
9.1.4
MRI assessments
Magnetic resonance imaging of the spine and sacroiliac joints will be performed at Screening, 
Week 48, Week 96, or WD Visit if MRI was performed more than 12 weeks prior to WD. 
Magnetic resonance imaging will be assessed centrally and scoring will be done by 2 
independent readers, who are blinded to both the order of the scans and to the treatment group, 
using a previously reported scoring system. In addition, a single reader assessment will be 
performed for change from Baseline (Week 48) evaluation in sacroiliac SPARCC and 
ASspIMRI-a in the Berlin-modification scores for all subjects that entered Part A.
According to the ASAS/OMERACT definition, the presence of bone marrow oedema (BMO) or 
osteitis is highly suggestive of SpA that is located in the typical anatomical areas (subchodral or 
periarticular bone marrow). There must be either more than 1 BMO lesion on 1 slice or a lesion 
that is present on at least 2 consecutive slices (Rudwaleit et al, 2009b). The ASAS/OMERACT
definition will be used for the classification of all Screening MRIs by the central readers. In 
practice, this is very similar to the SPARCC SIJ ≥2 definition of MRI which requires at least 
2 BMO lesions to be present. A recent paper showed that the sensitivity and specificity of the 
ASAS/OMERACT and SPARCC SIJ score ≥2 definitions of MRI positive were identical 
(sensitivity 0.80, specificity 0.76) (Weber et al, 2014). For the evaluation of the inflammatory 
changes over time, the SPARCC SIJ definition will be applied for all MRI images.
The SPARCC scoring method for lesions found on the MRI is based on an abnormal increased 
signal on the short-tau-inversion recovery (STIR) sequence, representing BMO (defined as an 
increased signal in bone marrow on a T2-weighted sequence, reflecting an increased
concentration of “free water” related to a bone lesion). Total SIJ SPARCC scores can range from 
0 to 72.
In addition to the method mentioned above, MRIs may be evaluated using other reading criteria.
9.1.5
Bath ankylosing spondylitis metrology index 
The BASMI characterizes the spinal mobility of subjects with AS. The BASMI is a 
disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical 
rotation; tragus to wall distance; lateral spinal flexion; modified Schober test; intermalleolar 
distance. Each of the 5 movements is scored according to the linear BASMI definition. The mean 
of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the 
subject’s limitation of movement due to their axSpA.
The BASMI assessments per visit are described in the schedule of study assessments Table 5.1.
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9.1.6
Total and nocturnal spinal pain NRS
The pain in the spine due to AS (ie, “How much pain of your spine due to spondylitis do you 
have?”); and pain in the spine at night due to AS (ie, “How much pain of your spine due to 
spondylitis do you have at night?”) (Sieper et al, 2009; van der Heijde et al, 2005; 
CPMP/EWP/556/95). Usually, a 10% difference (ie, a 1-point difference on a NRS ranging from 
0 to 10) is considered the MCID used to interpret scores (Dworkin et al, 2008). Pain experienced 
by axSpA subjects has also been measured with this assessment (Haibel et al, 2008).
The pain NRS assessments per visit are described in the schedule of study assessments Table 5.1.
9.1.7
Ankylosing spondylitis disease activity score (ASDAS)
The Ankylosing spondylitis disease activity score is comprised of a number of assessments 
which are scored by the subject and physician and multiplied by a proven formula (van der 
Heijde et al, 2009) as listed:
0.121 × Back pain (BASDAI Q2 result, see Section 9.1.2)
0.058 × Duration of morning stiffness (BASDAI Q6 result)
0.110 × PtGADA (see Section 9.2.3)
0.073 × Peripheral pain/swelling (BASDAI Q3 result)
0.579 × (natural logarithm of the CRP [mg/L] + 1) 
Back pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The variables related to ASDAS disease activity are defined as follows:

ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3

ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥1.3, <2.1

ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥2.1, ≤3.5

ASDAS-very High Disease activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS improvement are defined as follows:

ASDAS-CII: ASDAS reduction (improvement) of ≥1.1 relative to Baseline

ASDAS-MI: ASDAS reduction (improvement) of ≥2.0 relative to Baseline
The ASDAS will be calculated according to the assessment schedule in Table 5.1.
9.2
Assessment of other efficacy variables
9.2.1
Ankylosing spondylitis quality of life
The ASQoL, a validated disease-specific 18-item questionnaire, has been recently developed 
specifically for measuring health-related quality of life (HRQoL) in subjects with AS (Doward et 
al, 2003). The ASQoL has been used and has shown to be responsive in axSpA (Barkham et al, 
2009; Haibel et al, 2008). The ASQoL score ranges from 0 to 18 with higher score indicating 
worse HRQoL. A change of 1.8 points, which represents 10% of the possible score range, has 
been used as the MCID criteria to guide the interpretation of ASQoL score changes in previous 
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studies with a TNF-antagonist (van der Heijde et al, 2009; Davis et al, 2007). A change in 
ASQoL score of 2 points (ie, 10% of the total score range) will be used as the MCID to guide the 
interpretation of ASQoL score changes.
The ASQoL assessments per visit are described in the schedule of study assessments Table 5.1.
9.2.2
Work Productivity Survey
The WPS is an instrument used to assess productivity at work and within the home. The WPS 
has been found to be valid, reliable, and responsive to clinical changes in RA, PsA, and axSpA 
subjects (Osterhaus and Purcaru, 2014; Osterhaus et al, 2009). 
Site personnel should obtain information from the subject in order to complete this survey. 
 
 
 
 
 
 
 
 
 
 
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9.2.3
Patient’s global assessment of disease activity (NRS)
Subjects will score their global assessment of their disease activity in response to the question 
“How active was your spondylitis on average during the last week?” using a NRS where 0 is 
“not active” and 10 is “very active” (van Tubergen et al, in press 2015).
The PtGADA assessments per visit are described in the schedule of study assessments Table 5.1.
9.2.4
SF-36
The SF-36 (version 2, standard recall) is a 36-item generic HRQoL instrument that uses a recall 
period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), 
Role Physical (4 items), Bodily Pain (2 items), General Health (5 items),Vitality (4 items), Social 
Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and 1 item for 
perceived stability or change in health (Health Transition) during the last year. The concepts 
represented by these domains contribute to physical, mental, and social aspects of HRQoL.
In addition to domain scores, the PCS and MCS scores are calculated from the 8 domains 
(excluding the Health Transition item). Component scores appreciate the impact of each domain 
on physical and mental health status (Ware et al, 1994). Each of the 8 domain scores and the 
component summary scores range from 0 to 100, with a higher score indicating a better health 
status. The 2 component summary scores are standardized with a mean of 50 and a standard 
deviation (SD) of 10 in the general USA population. The MCIDs for SF-36 domains and 
component summaries are 2 to 4 points and 2 to 3 points, respectively (Ware et al, 2007).
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The SF-36 has been used and has shown to be responsive in axSpA (van Tubergen et al, in press 
2015; Haibel et al, 2008). The SF-36 will be administered per visit as described in the schedule 
of study assessments Table 5.1.
9.2.5
Enthesitis (MASES)
The Maastricht Ankylosing Spondylitis Enthesitis Score is an index that measures the severity 
(ie, intensity and extent) of enthesitis through the assessment of 13 entheses (bilateral 
costochondral 1, costochondral 7, anterior superior iliac spine, posterior iliac spine, iliac crest 
and proximal insertion of the Achilles tendon sites, and the fifth lumbar vertebral body spinous 
process) (Heuft-Dorenbosch et al, 2003), each scored as 0 or 1 and then summed for a possible 
score of 0 to 13.
Enthesitis assessments per visit are described in the schedule of study assessments Table 5.1.
9.2.6
Swollen and tender joint counts (44 joints evaluation)
The following 44 joints are to be examined for swelling and tenderness by the Principal 
Investigator, another delegated physician, or an appropriately qualified medical professional 
(based on local requirements) who has had documented training on how to perform these 
assessments correctly. Preferably the same assessor should evaluate the subject at each arthritis 
assessment.

Upper body (4) – bilateral sternoclavicular, and acromioclavicular joints.

Upper extremity (26) – bilateral shoulders, elbows, wrists (includes radiocarpal, carpal and 
carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I, II, III, 
IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, and V.

Lower extremity (14) – bilateral knees, ankles, and metatarsophalangeals (I, II, III, IV, and 
V).
The assessment for swelling and tenderness is made on 44 joints from the above list. Artificial 
and ankylosed joints are excluded from swelling and tenderness assessments.
The assessments per visit are described in the schedule of study assessments Table 5.1.
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Table 9.1:
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9.2.7
Physician’s global assessment of disease activity
The Investigator will assess the overall status of the subject with respect to the axSpA signs and 
symptoms and the functional capacity of the subject using a VAS where 0 is “very good, 
asymptomatic and no limitation of normal activities” and 100 is “very poor, very severe 
symptoms which are intolerable and inability to carry out all normal activities.”
This assessment by the Investigator should be made without any knowledge of the PtGADA.
The PhGADA will be completed as described in the schedule of study assessments Table 5.1.
9.2.8
Spinal mobility
In addition to the assessments performed for the BASMI, additional spinal mobility assessments 
include:

Occiput to wall distance

Chest expansion
Spinal mobility will be assessed as described in the schedule of study assessments Table 5.1.
9.2.9
Health status (EQ-5D)
The EQ-5D is comprised of a 5-item health status measures and a visual analog rating scale. 
Each of the 5 health states is divided into 3 levels: no problem, some or moderate problems, and 
extreme problems and is scored as 1, 2, and 3, respectively. The scored levels for 5 dimensions 
can be combined in a 5-digit number describing the respondent’s health profile or can be 
converted into a single summary index. The published mean Minimally Important Difference 
(MID) for the index value is 0.074 (range -0.011 to 0.140) and the SRM of 0.24 (range -0.05 to 
0.43) (Walters et al, 2005). The EQ-5D VAS records the respondent’s self-rated health status on 
a vertical 20cm scale, 0 to 100 graduated (0=worst imaginable health status, 100=best 
imaginable health status). The MID for VAS of 7 in cancer patients was published in 2007 by 
Pickard et al. (Pickard et al, 2007).This instrument is to be completed by the subject as described 
in the schedule of study assessments Table 5.1.
9.2.10
Resource utilization
Study specific questionnaires (standard eCRF modules) will be used to capture data regarding 
resources utilization during the study, ie:

Concomitant Medical Procedures

Health care provider consultations not foreseen by the protocol

Hospitalizations/Emergency Room visit (including length of stay)
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Site personnel should obtain information from the subject and corroborate data with known AEs 
and SAEs in order to complete this survey as described in the schedule of study assessments 
Table 5.1. The recall period for the questionnaire will be the previous 4 weeks.
9.2.11
Extra-articular assessments
The evolution of associated nonmusculoskeletal features including IBD, psoriasis and uveitis 
(including their severity), and flare rate history will be assessed as described in the schedule of 
study assessments Table 5.1. 
9.2.12
Fecal and serum calprotectin
The calgranulins, S100A8/S100A9 and S100A12, are calcium-binding proteins of the S100 
family. They are released from activated monocytes and granulocytes at local sites of 
inflammation during the early phase of the immune response. Extracellularly, they exert 
important pro-inflammatory effects, thereby providing stimulation and amplification of the 
innate immune reaction. Calgranulins can be measured in serum and stool, and have been found 
to be very sensitive markers of innate immune activation. Moreover, the S100A8/S100A9 
heterodimer, also called calprotectin, has been established for a long time as a fecal marker of 
disease activity in inflammatory bowel disease (Foell et al, 2009; Foell et al, 2007).
For all subjects, fecal and serum calprotectin will be examined for gut inflammation as described 
in the schedule of study assessments Table 5.1. Fecal calprotectin will be measured at Baseline, 
Week 48 and Week 96 and serum calprotectin will be measured at Baseline, Week 12, Week 24, 
3 to 5 days prior to Week 48, Week 72, and Week 96 for the completers. For escapers, an 
additional sample will be collected at the time when they are escaping (Week 0) and 12 weeks 
thereafter.
9.2.13
Inflammatory Bowel Disease Questionnaire assessment
The Inflammatory Bowel Disease Questionnaire is a validated quality of life questionnaire, 
which combines an assessment of symptoms as a result of IBD, the way the subject has been 
feeling in general, and how their mood has been over the previous 2 weeks.
The IBD-Q (Guyatt et al, 1989) is a widely used disease-specific instrument that has been 
validated to be reliable and reproducible in assessing HRQoL in CD. It contains 32 questions 
covering 4 domains of subjects’ lives (bowel symptoms, systemic symptoms, emotional function, 
and social function).
Subjects will be asked to answer questions relating to the impact of their CD on their HRQoL 
over the 2 weeks prior to their study visit using the IBD-Q. The IBD-Q must be completed by the 
subject prior to start any study-related activities.
Total score will be calculated for this study. An IBD-Q response is defined as a clinically 
meaningful improvement in the IBD-Q total score and corresponds to an increase in the IBD-Q 
total score ≥16 points from Baseline (Irvine, 1999). The IBD-Q remission is defined as an 
IBD-Q total score ≥170 points (Guyatt et al. 1989).
The IBD-Q will be completed by the subject as described in the schedule of study assessments 
Table 5.1.
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10
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACOGENOMICS VARIABLE(S)
Plasma samples for the measurement of CZP concentrations will be taken at Baseline and 
Weeks 4, 12, 24, 3 to 5 days prior to Week 48, and Weeks 60, 72, 84, 96/WD, and at the SFU 
visit 10 weeks after the last dose of study medication. For escapers plasma samples will be taken 
after the flare at Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer 
to Table 5.2 for details). These plasma samples may be used additionally for analyses of CZP 
and its constituent moieties using alternative methods and the results of those analyses may be 
reported separately.
Plasma samples for possible analyses of exploratory biomarkers will be taken at Baseline and 
Weeks 4, 12, 24, 3 to 5 days prior to Weeks 48, and Weeks 60, 72, 84, 96/WD, and at the SFU 
visit 10 weeks after the last dose of study medication. For escapers plasma samples will be taken 
after the flare at Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer 
to Table 5.2 for details). Selected biomarkers that may be analyzed are: MMP-3; BMP-2, -4, and 
-7, WNT1, WISP, Gremlin, DKK1, Sclerostin, Hedgehog proteins (Shh, Ihh, Dhh), Collagen 
turnover/cleavage products, collagen type X, VEGF, citrullinated vimentin fragments, cytokines: 
IL13, IL17 A and F, IL23, IL34, TGF-β, M-CSF, GM-CSF, CSF-1, sCSF1r levels.
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline
(Week 0), and for genomic and proteomics analysis only, at Weeks 12, 24, 3 to 5 days prior 
to Week 48, 72, and at Week 96/WD to enable exploratory evaluation of biomarkers relative to 
drug treatment and inflammatory and immune response processes. 
Samples will be moved from the Central Laboratory (ACM) at the end of the study to a 
long-term storage facility - BioStorage Technologies, GmbH - and will be stored at -80°C at the 
Central Laboratory facilities for up to 20 years.
11
ASSESSMENT OF IMMUNOGENICITY VARIABLES
Plasma samples for the measurement of ADAb and potentially NAb levels will be taken at 
Baseline (Week 0) and Weeks 4, 12, 24, 48, 60, 72, 84, 96, and the SFU visit (10 weeks after the 
last dose of study medication). For escapers, plasma samples will be taken after the flare at 
Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer to Table 5.2 for 
details).
The sampling, handling, and shipment of samples will be performed as detailed in the Laboratory 
Manual.
12
ASSESSMENT OF SAFETY
12.1
Adverse events
12.1.1
Definition of adverse event
An 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 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 72 of 173
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.
If a surgical procedure is performed during the study participation, the underlying condition 
should be reported as the AE (eg, "appendicitis" is the AE resulting in appendectomy).
The following laboratory values and physical findings are also to be considered AEs:

Laboratory value(s) that are out of reference range AND of clinical relevance, excluding 
Screening values

Laboratory value(s) that change from a subject's Baseline AND are of clinical relevance

Pre-existing physical findings (including vital sign measurements) that worsen compared 
with Baseline AND that are "clinically important"
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.
12.1.2
Procedures for reporting and recording adverse events
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)?”
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study.
12.1.3
Description of adverse events
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.
12.1.4
Follow up of adverse events
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.
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 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 73 of 173
clinically significant, or until the subject is lost to follow-up. If no follow-up is provided, the 
Investigator must provide a justification. The follow-up will usually be continued for 70 days 
after the subject has discontinued his/her IMP.
12.1.5
Rule for repetition of an adverse event
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
12.1.6
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
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 return for an early discontinuation visit.

The subject should immediately stop the intake of the IMP or be down-titrated as instructed 
at the early discontinuation visit. 

A Safety Follow-Up Visit should be scheduled 10 weeks after the subject has discontinued 
her IMP (last dose of IMP).
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/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 beginning of this protocol) 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 74 of 173
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 an SAE in the following circumstances: miscarriage, therapeutic abortion, 
and 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.
12.1.7
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the appropriate Drug Accountability forms and module of 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).
12.1.8
Safety signal detection
Regular monitoring of safety data collected during clinical studies will be performed as 
described in the Safety Signal Detection in the Ongoing Clinical Trials Charter for CZP.
Safety data including SAEs, AEs, vital signs, laboratory results, and electrocardiogram (ECG) 
data (as applicable) will be periodically reviewed by UCB.
The data from all studies with the same IMP will be reviewed to detect as early as possible any 
new safety concerns related to the IMP so that the Investigators, clinical study subjects, 
regulatory authorities, and IRBs/IECs will be informed in the most appropriate and timely 
manner.
12.2
Serious adverse events
12.2.1
Definition of serious adverse event
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

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 allergic bronchospasm requiring intensive treatment 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 75 of 173
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 subject 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 preexisting 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 preexisting 
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.)
12.2.2
Procedures for reporting serious adverse events
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 
30 days from the end of the study for each subject (which is usually the SFU visit), and to also 
inform participating subjects of the need to inform the Investigator of any SAE within this 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 76 of 173
period. Serious AEs that the Investigator 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 current version of 
the CZP Investigator’s Brochure (IB).
12.2.3
Follow up of serious adverse events
An SAE 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. 
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time.
12.3
Adverse events of interest
An AE of interest is any AE which is listed in the European Risk Management Plan, or meets 
another commitment requiring nonstandard expedited reporting, even if the AE does not fulfill 
the expedited reporting criteria of “serious,” “unexpected,” and “associated with the use of the 
drug.” Adverse events of interest include:

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 illness

Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
12.4
Immediate reporting of adverse events
The following AEs must be reported immediately:

SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product

AE of interest (see Section 12.3)
12.5
Anticipated serious adverse events
The following list of Anticipated SAEs has been identified, as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol.
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 12.2.2.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 77 of 173
JIA=Juvenile Idiopathic Arthritis; SAE=serious adverse event; CD=Crohn’s disease; RA=rheumatoid arthritis
a The lists of anticipated SAEs were based on the treatment-emergent SAEs with an incidence ≥0.5% in subject who 
participated in UCB sponsored placebo-controlled studies who received placebo (CD and RA safety pooling).
12.6
Laboratory measurements
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline
(Week 0), Weeks 12, 24, 32, 36, 3 to 5 days prior to Week 48, and Weeks 60, 72, 84, 96/WD, 
and at the SFU Visit (10 weeks after the last dose). Testing for HLA-B27, hepatitis B surface 
antigen, and antibodies to hepatitis C and HIV will be performed at Screening. The urinalysis 
will be performed with a dipstick, and in case of a positive outcome, on a clean catch urine 
sample sent to the central laboratory for analysis. The central laboratory will analyze and assess 
blood and urine samples for the following:
Table 12.1:
Anticipated serious adverse events in population independent of 
drug exposure
Population
Anticipated SAE(s)
Rheumatoid arthritis 
a
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Crohn’s disease a
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Perianal abscess
Abdominal pain
Ankylosing spondylitis
Ankylosing spondylitis
Psoriatic arthritis
Psoriatic arthritis
JIA
Juvenile arthritis
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 78 of 173
Table 12.2:
Laboratory measurements
Hematology
Chemistry
Urinalysis
Red blood cells
Sodium
pH
Hemoglobin
Potassium
Protein
Hematocrit
Chloride
Glucose 
Platelets
Bicarbonate
Blood
White blood cells
Total calcium
Esterase 
Neutrophils
Inorganic phosphorus
Microscopy (WBC, RBC, casts, 
crystals, bacteria) (Microscopy will 
be performed only when there are 
abnormalities on dipstick)
Lymphocytes
CRP
Monocytes
Creatine phosphokinase
Eosinophils
Glucose
Urine-sample to be collected for 
central-laboratory 
analysis 
only 
when there are abnormalities on 
dipstick
Basophils
Creatinine
Uric acid
Urea
Total protein
Others
Albumin
Hepatitis B surface antigen
Alkaline phosphatase
Antibodies to hepatitis C
Aspartate aminotransferase 
Antibodies to HIV
Alanine aminotransferase 
HLA-B27
Bilirubin
Fecal calprotectin
Total cholesterol
Serum calprotectin
CRP=C reactive protein; RBC=red blood cells; WBC=white blood cells; HIV=human immunodeficiency virus; 
HLA=human leukocyte antigen
12.7
Other safety measurements
12.7.1
Pregnancy testing
Pregnancy testing must be carried out for women of childbearing potential and will consist of 
serum testing at Screening and SFU, and urine testing at Baseline and W96/WD. 
12.7.2
Physical assessments
Physical examination will be performed at Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 
96/WD, and at the SFU Visit (10 weeks after the last dose). Physical examination findings will 
be recorded in the eCRF only at Screening. Clinically important abnormal changes in subsequent 
physical examinations will be recorded as AEs. Physical examinations must be documented in 
source documentation.
The following body systems will be examined:

General Appearance

Ear, Nose, and Throat
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 79 of 173

Eyes

Hair and Skin

Respiratory

Cardiovascular

Gastrointestinal

Musculoskeletal

Hepatic

Neurological (including limb reflexes)

Mental Status
In addition, the TB signs and symptoms questionnaire will be performed at Screening, Baseline, 
Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD Visit.
Weight is to be measured at Screening, Baseline, Week 48, and at Week 96/WD. Height will be 
measured at the Baseline Visit only.
12.7.3
Assessment and management of TB and TB risk factors
As TNF antagonists are known to be associated with significant risk of reactivation of LTB, 
appropriate rigorous precautions are being taken within the protocol (see Section 6.2 [Exclusion 
Criterion 16]) and Section 6.3.1 [Withdrawal Criterion 7]).
Signs and Symptoms
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s history. Sites commonly 
infected by TB include: the lungs, larynx, lymph glands, pleura, gastrointestinal system, 
genito-urinary tract (including renal), bones and joints, meninges, peritoneum, pericardium, and 
skin. This is not an exhaustive list and unusual presentations and areas of involvement should 
always be considered. 
Common symptoms with which the subject may present with include cough, blood in sputum, 
night sweats, lymphadenitis, joint pain/swelling, spinal deformity, headache/confusion, 
abdominal pain mimicking IBD, frequent or painful urination, scrotal mass in men and pelvic 
inflammatory disease in women as well as other symptoms, or nonspecific symptoms. This is not 
an exhaustive list and unusual presentations should always be considered.
Latent TB infection is defined as the absence of signs, symptoms (ie, evidence of organ-specific 
involvement), or physical findings suggestive of TB infection with a positive IGRA test (or 
2 indeterminate IGRA test results) and a chest x-ray (or other imaging) without evidence of TB 
infection. If the result of the IGRA test is indeterminate, the particular IGRA test previously 
performed may be repeated once; if positive or indeterminate on retest, the subject may not be 
randomized to study medication without further evaluation, treatment, and discussion with the 
Study Physician, if LTB infection is identified. (If active TB is identified, subject must undergo 
appropriate study specified withdrawal procedures.) The retest must be done during the 
protocol-defined Screening window.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 80 of 173
Note: If available, respiratory or other specimens must also be smear and culture negative for TB 
(CDC diagnosis of LTB infection, http://www.cdc.gov/TB/topic/testing/default.htm). 
Test Conversion
Tuberculosis test conversion is defined as a positive result (IGRA) for the current test but 
previous test results were negative (IGRA). All subjects with TB test conversion must 
immediately stop study drug administration. In case of a TB test conversion, the subject must be 
considered as having either a suspected new latent or an active TB infection and be promptly 
referred to an appropriate specialist (ie, pulmonologist, infectious disease specialist) for further 
evaluation. If test conversion indicates LTB infection, active TB, or nonmycobacterial TB 
infection then, per UCB TB working instructions, TB test conversion (confirmed) should be 
classified as due to LTB, active TB infection, or non-TB mycobacterial infection. Additional 
assessments (eg, blood tests or IGRA test, chest x-rays, or other imaging) should be performed as 
medically indicated.
Latent TB
In case the evaluation by the appropriate specialist indicates a new LTB, a prophylactic TB 
treatment (as described in Section 6.2, Exclusion Criterion 16) should be initiated and study 
medication can be continued no sooner than 4 weeks after start of prophylactic TB treatment, if it 
is deemed likely that prophylactic TB treatment is continued to completion.
In case no prophylactic treatment is initiated, the subject has to be withdrawn.
Every action should be discussed in advance with the Medical Monitor. Latent TB is an Adverse 
Event of special interest (AESI) and must be reported as such. 
Active TB/nontuberculosis mycobacterium
Subjects who develop active TB or nontuberculosis mycobacterium (NTMB) infection during 
the study (conversion demonstrated by IGRA) must be withdrawn from the study. The subject 
must be immediately discontinued from study medication and a WD Visit must be scheduled as 
soon as possible, but no later than the next scheduled visit. The subject should be encouraged to 
keep the SFU Visit as specified by the protocol. The TB must be documented as an SAE. 
Treatment should be immediately started.
Note that subjects with history of or active NTMB infection are excluded from the study 
regardless of prior or current therapy.
Confirmed active TB is an SAE and an AESI and must be captured on an SAE report form and 
provided to the Sponsor in accordance with SAE reporting requirements. As with all SAEs, 
periodic follow-up reports should be completed as per protocol requirement until such time as 
the TB infection resolves. 
Subjects who prematurely discontinue treatment for LTB or, in the opinion of the Investigator or 
Sponsor, are noncompliant with anti-TB therapy must discontinue further use of study 
medication and be immediately withdrawn. Once withdrawn from study treatment, subjects 
should return for the Week 96/WD Visit, complete all WD assessments, and complete an SFU 
Visit (10 weeks after the last dose of study medication).
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 81 of 173
12.7.3.1
Tuberculosis assessments
During conduct of the study, the TB assessment by IGRA (QuantiFERON TB GOLD In Tube 
test or Elispot, if QuantiFERON TB GOLD In Tube test is not available locally), should be 
repeated at Week 48 and Week 96/WD for all subjects. The test results will be reported as 
positive, negative, or indeterminate and must be reviewed by an experienced TB specialist, 
radiologist, or a pulmonologist. If the assessment by IGRA is positive or indeterminate on retest 
for subjects who were previously negative at Screening and not treated for LTB, the subject may 
not continue study treatment without further evaluation by a TB specialist, prophylactic 
TB-treatment, and discussion with the Medical Monitor, if LTB infection is identified. If active 
TB is identified, subject must undergo appropriate study-specified withdrawal procedures. The 
retest during Screening must be done during the protocol-defined Screening window.
12.7.3.2
Chest x-ray
A plain posteroanterior chest x-ray (or, if done, computed axial tomography of the chest) must be 
done within 3 months prior to the Screening Visit. The chest x-ray must be clear of signs of TB 
infection (previous or current) before first study medication administration. The chest x-ray 
should be repeated only if the TB test was confirmed positive or any further evidence is 
suggestive of potential TB infection (eg, exposure). Radiographic findings suggestive of inactive 
TB or active TB may include but are not limited to: apical fibrosis, pleural thickening, 
pulmonary nodules, fibrotic scars, calcified granulomas, upper lobe infiltrates, cavitations and 
pleural effusions, calcified lung nodules, calcified hilar lymph nodes, and pericardial 
calcification.
The chest x-ray (or, if done, computed axial tomography of the chest) must be negative for TB 
infection as determined by a qualified radiologist and/or pulmonary physician. Any new 
clinically significant findings post Baseline during physical examination or on chest x-ray must 
be documented in the source documents and eCRF as an AE.
12.7.3.3
Tuberculosis questionnaire
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will be completed at Screening, Baseline, and every 
12 weeks thereafter until Week 96/WD. The questionnaire will assist with the identification of 
subjects who may require therapy for TB. A subject who answers “Yes” to the question 
 
at Screening is excluded. A “Yes” response to any of the other 
questions within the questionnaire at Screening should trigger further careful assessment to 
determine if subject has latent or active TB (see Exclusion Criterion 16, Section 6.2). A “Yes” 
response to any of the questions during the study should trigger further assessments to determine 
if the subject has either LTB or active TB infection.
Subjects with a LTB infection must receive prophylactic therapy prior to continuing study 
medication (if allowed by prophylactic therapy specific protocol).
Subjects with active TB infection must be withdrawn from the study and will have further 
assessments.
12.7.3.4
Tuberculosis management
For inclusion in the study, see Section 6.2 (Exclusion Criterion 16).
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 82 of 173
It is the Sponsor’s requirement that all subjects who are on LTB treatment at Baseline must 
comply with the full therapy course (see Section 6.2, Exclusion Criterion 16). 
LTB infection and active TB identified during study
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of study medication and will be referred to an 
appropriate TB specialist (pulmonologist or infectious disease specialist) for further evaluation. 
Evidence of LTB infection is defined as the subject’s IGRA test converting to positive or 
indeterminate (and confirmed indeterminate on repeat), or the subject’s questionnaire history or 
physical examination indicating that TB infection or exposure may have occurred. Evidence of 
active TB includes, in addition to the aforementioned tests, signs and symptoms of organ 
involvement. In either situation, the subject should be carefully assessed by a TB specialist for 
active TB. Subjects diagnosed with active TB or LTB infection should receive appropriate TB or 
prophylaxis therapy. 
If a TB specialist excludes an active TB infection, the subject can proceed with the study 
medication no earlier than 4 weeks after the start of an appropriate prophylactic therapy. 
Any presumptive diagnosis or diagnosis of a TB infection (latent or active TB) is a reportable 
AESI. Confirmed active TB must be reported as a SAE, confirmed LTB as AESI (please see 
Section 12.2 and 12.3). The Investigator is to complete and submit the TB follow-up form 
provided.
The subject should be transferred to the care of their physician and managed according to the 
best available standard of care. Subjects identified as having converted to active TB during the 
study must be withdrawn and scheduled to return for the WD Visit as soon as possible but no 
later than the next scheduled study visit and complete all WD Visit assessments.
The subject should be encouraged to complete an SFU Visit 10 weeks after the last dose of study 
medication.
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed.
Subjects with LTB infection must not undergo IGRA testing. The IGRA test should be used for 
any protocol mandated monitoring.
Follow-Up information of suspected and confirmed TB cases should be provided to UCB at least 
after 3, 9, and 12 months of the start date of anti-TB treatment, including hematological and 
biochemical safety parameters, x-ray evolution data, and TB diagnostic procedures used to 
follow-up and confirm recovery of TB.
12.7.4
Vital signs 
Subjects should be sitting for 5 minutes prior and during the collection of blood pressure, pulse 
rate, and respiration rate measurements. 
Vital signs, including temperature, will be measured at all onsite visits including the SFU Visit 
(10 weeks after the last dose of study medication) with the exception of Visit 1. Respiration rate 
will be measured at Screening and Baseline only; and in addition at subsequent visits, if a subject 
experiences an AE.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
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Page 83 of 173
13
STUDY MANAGEMENT AND ADMINISTRATION 
13.1
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 CPM of the Sponsor 
within 24 hours and follow any local regulatory requirements.
13.2
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.
13.2.1
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, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies 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.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 84 of 173
The following data will be recorded directly in the ePRO tablet and will not appear in a source 
document as defined above:

Patient Reported Outcome questionnaires: SF-36, EQ-5D, PtGADA, BASDAI, BASFI, 
ASQoL, IBD-Questionnaire, Work Productivity Survey, Total and Nocturnal Spinal Pain 
Questionnaire
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 MRI records, must be saved and stored as instructed by UCB (or 
designee).
13.2.2
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 13.2.1.
13.3
Data handling
13.3.1
Case report form completion
This study will be using remote data capture (RDC); the Investigator is responsible for prompt 
reporting of accurate, complete, and legible data in the eCRF and in all required reports.
This study will also use an electronic device (Site Tablet) to capture patient reported outcomes
(see Section 13.3.2).
Serious adverse event reporting will be done using the SAE form (see Section 12.2.2) while also 
entering the event in the appropriate eCRF section. The safety database and the clinical database 
will be reconciled during the study and discrepancies will be corrected as needed.
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Access to the RDC will be given after training has been received. A training certificate will be 
provided and filed.
Detailed instructions on the use of the RDC will be provided in the eCRF Completion 
Guidelines.
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be re-approved by the Investigator. Any change or correction 
to the eCRF after saving must be accompanied by a reason for the change.
13.3.2
Electronic reporting outcome
Compared to the paper subject questionnaires the new electronic options have several advantages 
combining handheld devices in conjunction with online technologies in order to send subject 
self-assessments directly to a central server. The collected data could then be reviewed in real 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 85 of 173
time for improved subject symptom and compliance. The electronic patient reported outcome 
(ePRO) possibilities will be used in this study.
This study will use an electronic Site Tablet having a large screen and intuitive fingertip data 
entry to ensure all questionnaire data are captured appropriately, completely, and on time. Only 
subjects’ data will be collected with the tablets. Physicians’ data (joint counts and PhGADA) 
will be entered in the eCRF or collected on worksheets.
Access to the system will be given after training has been received. A training certificate will be 
provided and filed. The Investigator should maintain a list of personnel authorized to enter data 
into the ePRO device.
13.3.3
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. This study is performed using RDC; 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.
13.3.4
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.
13.4
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 other material in accordance with UCB procedures for the study.
Upon completion of the study, the monitor will conduct the following activities in conjunction 
with the Investigator, as appropriate:
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 86 of 173

Return of all study data to the Sponsor or its representative

Data clarification and/or resolution

Accountability, reconciliation, and arrangements for used and unused study drugs

Review of site study records for completeness

Discussion/reminder on archiving responsibilities
Further details will be given in the monitoring guidelines.
13.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, 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 
study master file.
13.6
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 
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).
13.7
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.
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24 Jan 2018
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Certolizumab Pegol
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Page 87 of 173
14
STATISTICS
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP).
14.1
Definition of analysis sets
The Enrolled Set (ES) will consist of all subjects who have given informed consent. 
The Open-Label Set (OLS) will consist of all subjects who receive at least 1 dose of study 
medication in the Open-Label Period of the study (Part A).
The Randomized Set (RS) will consist of all subjects randomized into Part B of the study. 
The Flared Set (FS) will consist of all subjects from the RS who experience a flare in Part B.
The Part B Full-Dose Set (FDS) will include all subjects from the RS who ever received a dose 
of CZP Q2W during Part B (including escape treatment).
The Safety Set (SS) will consist of all subjects in the ES who have received at least 1 dose of 
study medication. 
The Safety Set Part B (SSB) will consist of all subjects in the RS who have received at least 
1 dose of study medication in the Double-Blind Period of the study (Part B).
The Full Analysis Set (FAS) will consist of all subjects in the RS who have received at least 
1 dose of study medication in Part B, and have valid ASDAS measurements at Week 48 and at 
least 1 timepoint following Week 48. 
The Per Protocol Set (PPS) will be used to evaluate the sensitivity of the results of the primary 
efficacy analysis, which is based only on subjects who enter Part B. As such, the PPS will consist 
of subjects in the FAS without any major protocol deviations that may influence the validity of 
the data for the primary efficacy variable. Important protocol deviations will be defined and 
evaluated prior to unblinding.
The Pharmacokinetic Set A (PKSA) will consist of all subjects from the OLS who provide at 
least 1 PK sample during Part A.
The Pharmacokinetic Set B (PKSB) will consist of all subjects from the SSB who provide at 
least 1 PK sample during Part B.
14.2
General statistical considerations
All efficacy analyses for Part B will be performed using the RS. The FAS and PPS will be used 
for a sensitivity analysis on the primary endpoint only. Efficacy summaries for variables 
collected in Part A will be based on the OLS.
Summaries at the Week 48 timepoint for laboratory data and data collected via electronic device 
(Site Tablet) will be based on the assessments conducted 3 to 5 days prior to the Week 48 clinic 
visit.
The statistical analysis of the primary efficacy variable will account for the testing of multiple 
doses by using a fixed sequence testing procedure. The proportion of subjects who do not 
experience a flare (where flare is defined as ASDAS ≥2.1 on 2 consecutive visits or ASDAS 
>3.5 at any visit) will be compared between each CZP dose and placebo. The predefined order of 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 88 of 173
hypotheses testing, each at a 2-sided 0.05 significance level for the comparison between the 
given CZP dose and placebo, will be performed in the sequence shown below:
1. CZP 200mg Q2W vs placebo
2. CZP 200mg Q4W vs placebo
The second test will be performed irrespective of whether the first test is significant at the 0.05 
level or not. However, the second test will be interpreted as statistically significant only if the 
first test is significant at the 0.05 level as well.
14.3
Planned efficacy analyses
14.3.1
Analysis of the primary efficacy variable
The primary efficacy variable is the proportion of subjects who do not experience a flare. The 
primary analysis will be based on logistic regression. The odds ratio based on the proportion of 
subjects who do not experience a flare will be estimated and tested between treatment groups 
using a logistic regression model with factors of treatment group, geographic region, and mNY 
criteria (yes/no). Geographic region and mNY classification are also randomization stratification 
factors. The use of region as a stratification variable and as a factor in the model is intended to 
combine study centers in similar geographic regions. The geographic regions to be used will be 
pre-defined in the IXRS and in the SAP. Each CZP dose will be compared against placebo to 
establish superiority over placebo and will be tested sequentially at an alpha of 0.05 as outlined 
in Section 14.2. 
An approach based on the principles of nonresponse imputation (NRI) will be used to impute 
missing values. Specifically, if a subject withdraws from Part B at any point, they will be 
considered as having not responded to treatment. Therefore, they will be assumed to have 
experienced a flare during Part B for analysis purposes. If a subject has an intermittent missing 
ASDAS score (ie, a missing value at 1 visit but nonmissing values at the previous and 
subsequent visit), then the missing value will be ignored and flare will be based on the 
2 available values. If the ASDAS score is missing at 2 or more consecutive visits, then the 
subject will be treated as having experienced a flare (even if ASDAS scores are available after 
the missed visits).
Subgroup analyses based on age, gender, race, region, CRP level, ADAb status, and mNY 
criteria will be performed. These analyses will be done for the primary efficacy variable and will 
be based on descriptive statistics only.
14.3.2
Analysis of the secondary efficacy variables
14.3.2.1
Part A analysis
The secondary efficacy variables defined in Part A are as follows:

Percentage of subjects achieving sustained remission at Week 48

ASDAS disease activity (ASDAS-ID and ASDAS-MD, ASDAS-HD, ASDAS-vHD) at 
Week 48

ASDAS clinical improvement (ASDAS-MI and ASDAS-CII) at Week 48
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 89 of 173
The percentage of subjects achieving sustained remission, ASDAS-MI, and ASDAS-CII at 
Week 48 will be summarized using descriptive statistics (counts and percentages). Separate 
summaries will be done using NRI and observed case data.
Ankylosing Spondylitis Disease Activity Score disease activity at Week 48 will also be 
summarized using descriptive statistics, where counts and percentages are reported for each of 
the 4 categories. Two summaries will be provided: One will derive disease activity at Week 48 
using last observation carried forward (LOCF, impute using the last post-Baseline nonmissing 
result) for missing values and the other will be based on observed case data. 
All summaries of secondary efficacy variables in Part A will be based on the OLS.
14.3.2.2
Part B analysis
The time to flare will be analyzed using Kaplan-Meier methods. For those who meet the criteria 
for flare, the time will be defined as the length in days from randomization in Part B until the 
visit at which the criteria for flare were met. Subjects who discontinue the study without meeting 
the criteria for flare will be censored at the time of their last study visit. Subjects who complete 
the study without meeting the criteria for flare will be censored at their Week 96 visit. Between 
group differences will be analyzed with the log-rank statistic.
The changes from Baseline in ASDAS, BASDAI, BASFI, and BASMI at Week 96 for the RS 
will be compared between treatment groups using a mixed model for repeated measures 
(MMRM). The pattern of missingness for these variables is assumed to be missing at random 
(MAR). Subjects who enter Part B will have already demonstrated sustained remission through 
48 weeks on CZP 200mg Q2W. Many of these subjects will be randomized to receive placebo 
and will, therefore, be more likely to experience a flare. Postflare data for subjects who 
experience a flare (in any treatment group) will be treated as missing for the MMRM analysis. It 
is further assumed that most subjects who discontinue at this late stage in the study (ie, during 
Part B) will do so as a result of reduced efficacy. Therefore, missing efficacy data due to either 
flare or study treatment discontinuation should be dependent on the observed efficacy scores, but 
independent of unobserved data. 
The MMRM model will include Baseline score as a fixed-effect covariate, treatment group, 
region, mNY criteria (yes/no), and visit as fixed-effect categorical factors, and Baseline-by-visit 
and treatment group-by-visit as interaction terms. An unstructured correlation pattern will be 
used to estimate the variance-covariance of the within-subject repeated measures. Tables will 
present the adjusted means for placebo and the CZP doses (200mg Q2W and 200mg Q4W), the 
respective difference to placebo, the corresponding p-value, and 95% CI. 
Change from Baseline in SIJ SPARCC and spine ASspIMRI-a in the Berlin modification scores 
at Week 96 will be compared between treatment groups using analysis of covariance 
(ANCOVA) for observed values only (ie, no imputation). The model will include Baseline score, 
treatment group, region, and mNY criteria (yes/no). Tables will present the adjusted means for 
placebo and the CZP doses (200mg Q2W and 200mg Q4W), the respective difference to placebo, 
the corresponding p-value, and 95% CI. 
The binary secondary efficacy variables (ASDAS-MI, ASDAS-CII, ASAS20, ASAS40, 
ASAS5/6, ASAS PR, and BASDAI50 response) at Week 96 will be analyzed using a logistic 
regression. The odds ratio of the responder rates at Week 96 will be estimated and tested 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 90 of 173
between treatment groups using a logistic regression model with factors of treatment group, 
region, and mNY criteria (yes/no). Tables will present the responder rates for placebo, 
CZP 200mg Q2W, and CZP 200mg Q4W, the respective effect estimates (adjusted odds ratio 
with reference to placebo), p-values, and 95% CIs. Subjects with a missing responder status at 
Week 96 will be treated as a nonresponder for analysis purposes (ie, NRI).
Ankylosing Spondylitis Disease Activity Scores (ASDAS-ID, ASDAS-MD, ASDAS-HD, 
ASDAS-vHD) will be summarized by treatment group using summary statistics (counts and 
percentages) based on observed case data.
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observations [n], mean, median, SD, minimum, and maximum) will be provided by treatment 
group for the secondary efficacy variables. The descriptive analyses will be covered in the tables 
summarizing the variables over time. This will include a summary of the actual values, change 
from Baseline (Week 0), and change from randomization Baseline (Week 48). The statistical 
comparisons described for secondary efficacy variables are not part of the multiplicity-controlled 
testing procedure described in Section 14.2. The p-values reported for these analyses will not be 
adjusted for multiplicity and will be considered nominal. All analyses and summaries of 
secondary efficacy variables in Part B will be based on the RS.
14.3.2.3
Part B analysis for subjects who experience a flare
For subjects who experience a flare during Part B, the secondary efficacy variables listed below 
will be analyzed. The timepoint for these secondary efficacy analyses will be at Escape 
Week 12).

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) 

ASDAS clinical improvement (ASDAS-CII, ASDAS-MI)

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

Change from Baseline in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in MRI
These variables will be summarized by treatment group using descriptive statistics. For the 
binary response variables (ASDAS-CII, ASDAS-MI, ASAS20, ASAS40, ASAS5/6, and ASAS 
PR), counts and percentages at Escape Week 12 visit will be displayed. For comparative 
purposes, the tables will also include the responder counts and percentages at the visit where 
flare criteria were met. ASDAS disease activity will be summarized in a similar way based on 
the 4 categories.
For the continuous variables (ASDAS, BASDAI, BASFI, BASMI), quantitative descriptive 
statistics by treatment group will be displayed. This summary will include the actual results at
Escape Week 12, change from Baseline (Week 0), change from randomization Baseline 
(Week 48), and change from the visit in which the flare occurred. 
All Part B summaries after subjects experience a flare will be based on observed case data and 
will use the FS.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 91 of 173
14.3.3
Other efficacy analyses
14.3.3.1
Part A
The other efficacy variables for Part A as outlined in Section 4.1.3.1 will be summarized by visit 
and treatment group using descriptive statistics for the timepoint itself and for the change from 
Baseline. This will be done for the OLS using observed case data and with imputation using 
LOCF. Further details are described in the SAP.
Tables for the binary variables will display the responder rates for the various timepoints over 
time. This will be done for the OLS using observed case data and with imputation using NRI.
14.3.3.2
Part B
Treatment group comparisons for both CZP groups vs placebo will be performed based on the 
change from Baseline in other selected efficacy variables. These analyses will be performed 
using an ANCOVA model with variables of Baseline score, treatment group, region, and mNY 
criteria (yes/no) in the model. The treatment differences and corresponding 95% CIs will be 
calculated based on the adjusted means. Missing values will be imputed using LOCF. This 
analysis approach will be used for the following variables:

Total spinal pain
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
PtGADA

Morning stiffness (BASDAI 5 and 6)

SF-36 PCS, MCS, and physical function domain

Fatigue NRS

ASQoL
Such analyses will also be done for the following continuous variables: ASDAS, BASDAI, 
BASFI, and BASMI will be analyzed using a MMRM similar to the one specified in 
Section 14.3.2.2 at timepoints not covered in the secondary efficacy analyses. Additionally, 
ASDAS-MI, ASDAS-CII, ASAS, and BASDAI50 response variables will be analyzed using a 
logistic regression model similar to the one specified for binary response variables in 
Section 14.3.2.2 at timepoints not covered in the secondary efficacy analyses. 
These comparisons are not part of the multiplicity-controlled testing procedure described in 
Section 14.2. The p-values reported for these analyses will not be adjusted for multiplicity and 
will be considered nominal. Exploratory statistical comparisons will also be performed for WPS 
scores using the nonparametric bootstrap-t method. This will be explained in greater detail in the 
SAP.
All other efficacy variables will be summarized descriptively by visit and treatment group using 
observed case and imputed data based on the RS.
14.3.3.3
Part B analysis for subjects who experience a flare
The other efficacy variables for subjects who experience a flare in Part B as outlined in 
Section 4.1.3.3 will be summarized by visit and randomized treatment group using descriptive 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 92 of 173
statistics for the timepoint itself and for the change from Baseline. A subset of variables will 
summarize the change from randomization Baseline (Week 48) and the change from the visit at 
which the flare occurred. This will be done for the FS using observed case data.
14.4
Planned safety and other analyses
14.4.1
Safety analyses
The frequency of all AEs by study period (Part A and Part B) will be presented separately by 
System Organ Class, high-level term, and preferred term and for Part B by each treatment group. 
The data will be displayed as number of subjects experiencing the AEs, percentage of subjects, 
and number of AEs. Data will also be corrected for exposure by 100 patient years.
Laboratory evaluations and vital signs will be analyzed over time in the SS and SSB for observed 
cases and at the end of treatment.
14.4.2
Pharmacokinetic and immunogenicity analysis
Certolizumab pegol plasma concentrations will be tabulated and summarized by treatment group 
for each visit at which samples were taken using the geometric mean, 95% CI, geometric 
coefficient of variation, arithmetic mean, arithmetic SD, median, minimum, and maximum. 
Immunogenicity will be assessed through listing of individual results by subject and summary 
tables. Immunogenicity data will be correlated with PK and efficacy readout. In addition, 
immunogenicity will be correlated with possible safety findings.
14.5
Handling of protocol deviations
Important protocol deviations are deviations from the protocol that could potentially have a 
meaningful impact on study conduct or on the primary efficacy outcomes for an individual 
subject. The criteria for identifying important protocol deviations will be defined within the 
appropriate protocol-specific document. Important protocol deviations will be reviewed as part 
of the ongoing data cleaning process and all important deviations will be identified and agreed 
upon prior to unblinding to confirm exclusion from analysis sets.
14.6
Handling of dropouts or missing data
For the primary efficacy variable (percentage of subjects in Part B who do not experience a flare), 
an approach based on the principles of NRI will be used to impute missing values. Specifically, 
if a subject withdraws from Part B at any point, they will be considered as having not responded 
to treatment. Therefore, they will be assumed to have experienced a flare during Part B for 
analysis purposes. If a subject has an intermittent missing ASDAS score (ie, a missing value at 
1 visit but nonmissing values at the previous and subsequent visit), then the missing value will be 
ignored and flare will be based on the 2 available values. If the ASDAS score is missing at 2 or 
more consecutive visits, then the subject will be treated as having experienced a flare (even if 
ASDAS scores are available after the missed visits).
For the time to flare endpoint, the rules as described above for the primary endpoint will be 
applied to account for missing data when determining whether or not a subject experienced a 
flare. Subjects who discontinue the study without meeting the criteria for flare will be censored 
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 93 of 173
at the time of their last study visit. Subjects who complete the study without meeting the criteria 
for flare will be censored at their Week 96 visit.
Selected continuous secondary efficacy variables will be analyzed using MMRM methods (see 
Section 14.3.2.2 for details). Missing data for binary response secondary efficacy variables will 
be handled using NRI. Secondary variables related to MRI will be analyzed based on the 
observed case data.
In general, other efficacy variables will be summarized as both observed case and with 
imputation (NRI for binary response variables and LOCF for continuous variables), unless 
otherwise specified. Nonresponse imputation is implemented by treating missing data for binary 
response variables as a nonresponse. The LOCF summaries will impute missing continuous data 
using the last post-Baseline nonmissing result. In the event that a subject has no post-Baseline 
data for a given continuous variable, no imputation will be performed.
14.7
Planned interim analysis and data monitoring
A database lock may be performed and an interim study report may be written, if required. The 
main focus of this interim analysis would be the efficacy and safety up to a certain treatment 
timepoint eg, after Week 48.
Regular monitoring of safety data collected during clinical studies will be performed as 
described in the Safety Signal Detection in the Ongoing Clinical Trials Charter for CZP.
A specific data monitoring, steering, or evaluation committee is not planned for this study.
14.8
Determination of sample size
It is anticipated that approximately 210 subjects will be randomized in a 1:1:1 ratio to the 
CZP 200mg Q2W, CZP 200mg Q4W, and placebo treatment groups. The primary efficacy 
analysis is based on the proportion of subjects who do not experience a flare during Part B of the 
study. The proportion of subjects who do not experience a flare during Part B is assumed to be 
80%, 75%, and 45% for the CZP 200mg Q2W, CZP 200mg Q4W, and placebo treatment groups, 
respectively. Given these assumptions, a sample size of 70 subjects per group provides 98% 
power to detect a significant difference between the CZP 200mg Q2W dose and placebo and 
94% power to detect a significant difference between the CZP 200mg Q4W dose and placebo 
using a 2-sided significance level of 0.05. 
Given that subjects enter Part B only if they have achieved sustained remission in Part A, it is 
necessary to estimate the number of subjects needed to enroll in Part A. It is assumed that 
approximately 28% of subjects enrolled in Part A will achieve sustained remission and qualify 
for Part B. This means that about 750 subjects will be enrolled in Part A in order to have 
210 subjects who are randomized into Part B. Subject response to treatment will be evaluated on 
an ongoing basis as subjects enroll in Part A, and the number of subjects enrolled will be adapted 
accordingly in order to achieve 210 subjects randomized to Part B.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
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Page 94 of 173
15
ETHICS AND REGULATORY REQUIREMENTS
15.1
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 written 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.
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.
15.2
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 
subject identifying information and medical emergency contact information. The Investigator 
will instruct the subject to keep the card with him/her at all times.
15.3
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.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 95 of 173
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.
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.
15.4
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).
15.5
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.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 96 of 173
16
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.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 97 of 173
17
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Clinical Study Protocol
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AS0005
Confidential
Page 98 of 173
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Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 99 of 173
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Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 100 of 173
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Clinical Study Protocol
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AS0005
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Page 101 of 173
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Certolizumab Pegol
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Page 102 of 173
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Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 103 of 173
18
APPENDICES
18.1
ASAS classification criteria for axSpA
Imaging criteria
ASAS clinical criteria for axSpA
Sacroiliitis (MRI or radiographs a) plus ≥1 SpA 
feature
HLA-B27 plus ≥2 other SpA features
SpA features b
Inflammatory back pain c
Arthritis
Enthesitis (heel)
Uveitis
Dactylitis
Psoriasis
Crohn’s disease/ulcerative colitis
HLA-B27
Elevated CRP
ASAS=Assessment of SpondyloArthritis International Society; CRP=C-reactive protein; MRI=magnetic resonance 
imaging; HLA-B27=human leukocyte antigen B27; NSAID=nonsteroidal anti-inflammatory drug; 
SpA=spondyloarthritis
aActive inflammatory lesions of sacroiliac joints with definite bone marrow oedema/osteitis suggestive of 
sacroiliitis associated with spondyloarthritis in MRI or radiographic sacroiliitis grade 2 to 4 bilaterally or grade 3 
to 4 unilaterally according to modified NY criteria.
b ‘Family history for SpA’ and ‘Good response to NSAIDs’ are excluded as SpA feature criteria.
c Inflammatory back pain according to ASAS criteria for axSpA defined as the presence of 4 out of 5 of the 
following parameters:
1) age at onset <45 years
2) insidious onset
3) improvement with exercise 
4) no improvement with rest
5) pain at night (with improvement upon getting up)
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Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 104 of 173
18.2
Corticosteroid equivalent doses
Table 18.1:
Corticosteroid equivalent doses (with reference to prednisone 10mg 
dose)
a
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10mg
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Dexamethasone
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a Source: Meikle and Tyler, 1977
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Certolizumab Pegol
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Page 105 of 173
18.3
Protocol Amendment 1
Rationale for the amendment
This substantial amendment includes additional efficacy variables for subjects entering Part A 
and Part B of the study, as well as a completely new list of other efficacy variables for those 
subjects who experience a flare in Part B. For the purposes of analysis, 4 new analysis sets were 
defined; 2 of which will be used in the PK analysis, 1 which will be used in the efficacy analysis 
of subjects experiencing a flare in Part 2, and 1 which will be used to evaluate safety in subjects 
who ever received treatment with full-dose CZP during Part B of the study. Several clarifications 
were made including the timepoint for the assessment of the secondary efficacy variables for 
subjects who experience a flare in Part B, HLA-B27 as a Screening laboratory assessment, and 
the assessments to be performed 3 to 5 days prior to Week 48. Inconsistencies in the naming of 
Week 96 visit and assessments were corrected, study personal information was updated, and 
minor editorial changes were made.
Modifications and changes
Global changes
The following changes were made throughout the protocol:

Assessment of ePRO outcomes and CRP at Week 48 to be performed 3 to 5 days prior to 
Week 48. This was updated throughout the protocol.

HLA-B27 removed from Baseline and included in Screening. 

The term “Investigator's AS” was changed to ‘PhGADA’.

Anti-CZP antibody was abbreviated to ADAb throughout the document.

Timepoint for assessment of secondary efficacy variables for subjects who experience a flare 
in Part B was changed from “Week 96 or a later timepoint” to “Escape Week 12”.

The variable “spinal mobility” was added as 2 variables as follows:

Change from Baseline in spinal mobility, as assessed by occiput to wall distance. 

Change from Baseline in spinal mobility as assessed by chest expansion.

Efficacy variable total and nocturnal spinal pain has been changed to: total spinal pain (part 
of the ASAS) and nocturnal spinal pain has been separated from ASAS core components.

Addition of variables to be assessed for subjects experiencing flare in Part B.

Additional analysis sets for assessment of pharmacokinetic variables and for assessment of 
variables in subjects experiencing flare in Part B.

Completion/Withdrawal Visit is now referred to as Week 96/Withdrawal Visit throughout the 
protocol.

Serum calprotectin analysis was added in addition to the existing fecal calprotectin analysis 
and references to “calprotectin” alone were separated into “serum calprotectin” and “fecal 
calprotectin”.

Correction of errors.
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AS0005
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Page 106 of 173
It is to be noted that typographical updates were made in the document, but not listed 
individually in the specific changes list.
Specific changes
Change #1
STUDY CONTACT INFORMATION
Name:
Address:
8010 Arco Corporate Drive Raleigh,
NC 27617
Phone:
Fax:
Has been changed to:
Name:
Address:
Alfred-Nobel-Strasse 10
40789 Monheim, Germany
Phone:
Fax:
Change #2
STUDY CONTACT INFORMATION
Name:
Address:
8010 Arco Corporate Drive Raleigh,
NC 27617
Phone:
Fax:
Has been changed to:
Name:
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 107 of 173
Change #3
The following abbreviations were added:
ADAb
anti-CZP antibody
ASAS20, 40
Assessment of SpondyloArthritis International Society 20%, 40% response 
criteria
FDS
Full Dose Set
FS
Flared Set
M-CSF
macrophage colony-stimulating factors
PKSA
Pharmacokinetic Set A
PKSB
Pharmacokinetic Set B
Change #4
1. 
SUMMARY, paragraph 1
Study AS0005 is a multicenter, open-label (Part A) followed by a randomized, double-blind, 
parallel-group, placebo-controlled clinical study (Part B) to evaluate the efficacy, safety, 
pharmacokinetics (PK), and immunogenicity of certolizumab pegol (CZP) in adult subjects with 
active axial spondyloarthritis (axSpA) in sustained remission who continued either on full-dose 
treatment (CZP 200mg every 2 weeks [Q2W]), on a dose reduction (CZP 200mg every 4 weeks 
[Q4W]) or withdrawal of CZP treatment. The study includes 2 parts an Open-Label Run-In 
Period for 48 weeks (Part A) followed by a Double-Blind Period for 48 weeks (Part B) with 
3 treatment arms (200mg CZP Q2W [referred to as full-dose], 200mg CZP Q4W [referred to as 
half-dose], and placebo), and a Safety Follow-Up (SFU) Period for 10 weeks after the last dose 
of study medication.
Has been changed to:
Study AS0005 is a multicenter, open-label (Part A) followed by a randomized, double-blind, 
parallel-group, placebo-controlled clinical study (Part B) to evaluate the efficacy, safety, 
pharmacokinetics (PK), and immunogenicity of certolizumab pegol (CZP) in adult subjects with 
active axial spondyloarthritis (axSpA) in sustained remission who continued either on full-dose 
treatment (CZP 200mg every 2 weeks [Q2W]), on a dose reduction (CZP 200mg every 4 weeks 
[Q4W]) or withdrawal of CZP treatment (placebo). The study includes: an Open-Label Run-In 
Period of 48 weeks (Part A) followed by a Double-Blind Period of 48 weeks (Part B) with 
3 treatment arms (200mg CZP Q2W [referred to as full-dose], 200mg CZP Q4W [referred to as 
half-dose], and placebo), and a Safety Follow-Up (SFU) Period for 10 weeks after the last dose 
of study medication.
Change #5
1. 
SUMMARY, paragraphs 8, 9, and 10
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated at Week 96 or a later timepoint, if applicable: 1) ASDAS disease activity 
and clinical improvement, 2) ASAS20, ASAS40, ASAS5/6, and ASAS PR response, and 3) 
Change from Baseline in ASDAS, BASDAI, BASFI, BASMI, and MRI.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 108 of 173
Further, other efficacy variables for Part A, and Part B are listed in Section 4.1.3.1 and 
Section 4.1.3.2, respectively.
Pharmacokinetic and pharmacogenomic variables are listed in Section 4.1.3.3, and 
immunological variables are listed in Section 4.3.
Has been changed to:
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated at Escape Week 12: 1) ASDAS disease activity and clinical 
improvement, 2) ASAS20, ASAS40, ASAS5/6, and ASAS PR response, and 3) change from 
Baseline in ASDAS, BASDAI, BASFI, BASMI, and 4) change from Baseline in sacroiliac 
SPARCC and ASspIMRI-a in the Berlin modification scores.
Further, other efficacy variables for Part A, and Part B and for subjects who experience a flare in 
Part B are listed in Section 4.1.3.1, Section 4.1.3.2, and Section 4.1.3.3, respectively.
Pharmacokinetic and pharmacogenomic variables are listed in Section 4.2 and immunological 
variables are listed in Section 4.3.
Change #6
2.5. 
RATIONALE, paragraph 4
For axSpA patients suffering from gut inflammation, the QoL will be assessed with an 
inflammatory bowel disease questionnaire (IBD-Q) and, in addition to this, an analysis of 
calprotectin in stool samples (a protein associated with acute gut inflammation) will be 
performed to assess the correlation between gut inflammation, quality of life, and response to 
treatment with CZP.
Has been changed to:
For axSpA patients suffering from gut inflammation, the QoL will be assessed with an 
inflammatory bowel disease questionnaire (IBD-Q) and, in addition to this, an analysis of 
calprotectin in stool and serum samples (a protein associated with acute gut inflammation) will 
be performed to assess the correlation between gut inflammation, quality of life, and response to 
treatment with CZP.
Change #7
3. 
STUDY OBJECTIVES
The following sentence was inserted as the last paragraph:
Subjects who meet the criteria of flare during Part B and who crossed-over to full-dose treatment 
(CZP 200mg Q2W) are regarded as escapers. 
Change #8
Section 4.1.2.3: Secondary efficacy variables for subjects who experience a flare in Part B, 
paragraph 1
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated 12 weeks after escape and at Week 96, or a later timepoint, if applicable. 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 109 of 173
The minimum full-dose treatment for the escapers is 12 weeks and could extend beyond the 
Week 96 visit.
Has been changed to:
The following are secondary efficacy variables for subjects who experience a flare in Part B. 
These will be evaluated at Escape Week 12.
Bullet #3 has been modified:

Change from Baseline in ASDAS, BASDAI, BASFI, BASMI, and sacroiliac SPARCC and 
ASspIMRI-a in the Berlin modification scores.
Change #9
4.1.3.1 
Other efficacy variables for subjects entering Part A
Bullet #2, 3, 6, and 20 were amended

Change from Baseline in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in sacroiliac SPARCC and spine ASspIMRI-a in the Berlin 
modification scores 

Change from Baseline in all individual ASAS core components

Total and nocturnal spinal pain (Numeric Rating Scale [NRS])

Correlation between fecal calprotectin, and IBD-Q
Has been changed to:

Change from Baseline in ASDAS, BASDAI and BASMI

Change from Baseline in sacroiliac SPARCC and ASspIMRI-a in the Berlin modification 
scores 

Change from Baseline in all individual ASAS core components

Total spinal pain (Numeric Rating Scale [NRS])

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP
Inserted bullet #2, 4, 7, 8, 9, 10, and 21

BASDAI50 response

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI)

Change from Baseline in nocturnal spinal pain (NRS)

Change from Baseline in spinal mobility, as assessed by occiput to wall distance 

Change from Baseline in spinal mobility as assessed by chest expansion

Change from Baseline in PhGADA 

Change from Baseline in serum calprotectin
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 110 of 173
Change #10
4.1.3.2 Other efficacy variables for subjects entering Part B
Bullets #6 and 18 were amended

Change from Baseline in all individual ASAS core components

Total and nocturnal spinal pain (Numeric Rating Scale [NRS])

Correlation between fecal calprotectin and IBD-Q
Has been changed to:

Change from Baseline in all individual ASAS core components

Total spinal pain (NRS)

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP
Inserted bullet #1, 2, 3, 4, 5, 7, 8, 9, 10, 15, and 23

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

BASDAI50 response

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI)

Change from Baseline in ASDAS, BASDAI, and BASMI

Change from randomization Baseline (Week 48) in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in nocturnal spinal pain (NRS)

Change from Baseline in spinal mobility, as assessed by occiput to wall distance

Change from Baseline in spinal mobility assessed by chest expansion

Change from Baseline in PhGADA

Change from randomization Baseline (Week 48) in sacroiliac SPARCC and spine 
ASspIMRI-a in the Berlin modification scores

Change from Baseline in serum calprotectin
Change #11
Inserted section 4.1.3.3. Other efficacy variables for subjects who experience a flare in Part B 
The following other efficacy variables for subjects who experience a flare in Part B will be 
evaluated at all scheduled study visits where the assessment is performed following Escape 
Week 0.

ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and 
clinical improvement (ASDAS-CII, ASDAS-MI) 

ASAS20, ASAS40, ASAS5/6, and ASAS PR response

Change from Baseline in ASDAS, BASDAI, and BASMI
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 111 of 173

Change from randomization Baseline (Week 48) in ASDAS, BASDAI, BASFI, and BASMI

Change from the visit at which the flare occurred in ASDAS, BASDAI, BASFI, and BASMI

Change from Baseline in all individual ASAS core components
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
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
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
Change from Baseline in spinal mobility assessed by chest expansion

Change from Baseline in PhGADA

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Change from Escape Week 0 in sacroiliac SPARCC and ASspIMRI-a in Berlin modification 
scores

Change from Baseline in WPS 

Health status as assessed by the EQ-5D: domains, VAS actual score, and change from 
Baseline in VAS score

Change from Baseline in MASES

Number of uveitis flares

Number of IBD exacerbations

Change from Baseline in fecal calprotectin

Change from Baseline in serum calprotectin

Change from Baseline in the IBD-Q

Correlation between fecal calprotectin, serum calprotectin, IBD-Q, and CRP

Number of psoriasis exacerbations (in subjects with concurrent psoriasis)

Change from Baseline in all SF-36 domains, SF-36 PCS, and SF-36 MCS
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 112 of 173

Resources utilization: concomitant medical procedures, healthcare provider consultations not 
foreseen by the protocol, hospitalizations/emergency room visits
Change #12
4.2.3
Pharmacogenomic variables
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline, 
and, for genomic and proteomics analysis only, additionally at Weeks 12, 24, 48, and 96 to 
enable exploratory evaluation of biomarkers relative to drug treatment and inflammatory and 
immune response processes. The samples will be stored at -80°C at the Central Laboratory
facilities for up to 20 years or according to local laws.
Has been changed to:
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline, 
and, for genomic and proteomics analysis only, additionally at Weeks 12, 24, 48, 72, and 96/WD
to enable exploratory evaluation of biomarkers relative to drug treatment and inflammatory and 
immune response processes. The samples will be stored at -80°C at the Central Laboratory 
facilities for up to 20 years or according to local laws.
Change #13
4.4.
Safety variables
Safety variables to be assessed are AEs, physical examination, chest x-ray, and measurements of 
laboratory parameters (hematology, biochemistry, and urinalysis). 
Adverse events will be solicited at every visit, and recorded and coded according to the latest 
version of the Medical Dictionary for Regulatory Activities® criteria used at UCB at the time of 
analysis.
Physical examination findings will be recorded in the electronic Case Report Form (eCRF) only 
at Screening. Clinically relevant changes in subsequent physical examinations will be recorded 
as AEs.
Clinical laboratory values (hematology, biochemistry, and urinalysis) will be collected and 
assessed at Screening, Baseline, at Weeks 12, 24, 32, 36, and every 12 weeks thereafter through 
to study Completion/WD Visit and at the SFU Visit 10 weeks after the last dose of study 
medication. C-reactive protein values will be collected and assessed at Screening, Baseline, 
Weeks 2, 4, 12, 24, 32, 36, 3 to 5 days prior to Week 48, 48, 50, 52, and every 4 weeks thereafter
through to study Completion/WD Visit. For escapers, different schedules for clinical laboratory 
values and CRP apply after start of the escape treatment (refer to Table 5.2).
At Screening, Week 48, and Week 96, all subjects will have an IGRA test (QuantiFERON TB 
GOLD In Tube test or another WHO-validated IGRA test such as Elispot, if QuantiFERON TB 
GOLD In Tube test is not available locally). A chest x-ray (or, if done, computed axial 
tomography of the chest) at Screening (or up to 3 months prior to Screening) must be read and 
reported consistent with standard clinical reporting practice by an experienced TB specialist, 
radiologist or a pulmonologist, who is specifically required to look for signs of active TB or 
signs of past/inactive TB infection. The official report of the imaging must specifically indicate 
the absence of findings suggestive of current active TB or prior inactive TB. In addition to a 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 113 of 173
physical examination done intermittently throughout the study, subjects will be evaluated at 
Screening, Baseline, and every 12 weeks thereafter, including the Completion/WD Visit, for 
signs and symptoms of latent or active TB infection and risk factors for exposure to TB using the 
TB questionnaire.
Has been changed to:
Safety variables to be assessed are AEs, physical examination, vital sign measurements, chest 
x-ray, and measurements of laboratory parameters (hematology, biochemistry, and urinalysis). 
Adverse events will be solicited at every visit, and recorded and coded according to the latest 
version of the Medical Dictionary for Regulatory Activities® criteria used at UCB at the time of 
analysis.
Physical examination findings will be recorded in the electronic Case Report Form (eCRF) only 
at Screening. Clinically relevant changes in subsequent physical examinations will be recorded 
as AEs.
Clinical laboratory values (hematology, biochemistry, and urinalysis) will be collected and 
assessed at Screening, Baseline, at Weeks 12, 24, 32, 36, and every 12 weeks thereafter through 
to study Week 96/WD Visit and at the SFU Visit 10 weeks after the last dose of study 
medication. C-reactive protein values will be collected and assessed at Screening, Baseline, 
Weeks 2, 4, 12, 24, 32, 36, 3 to 5 days prior to Week 48, Week 50, Week 52, and every 4 weeks 
thereafter through to study Week 96/WD Visit. For escapers, different schedules for clinical 
laboratory values and CRP apply after start of the escape treatment (refer to Table 5.2).
At Screening, Week 48, and Week 96, all subjects will have an IGRA test (QuantiFERON TB 
GOLD In Tube test or another WHO-validated IGRA test such as Elispot, if QuantiFERON TB 
GOLD In Tube test is not available locally). A chest x-ray (or, if done, computed axial 
tomography of the chest) at Screening (or up to 3 months prior to Screening) must be read and 
reported consistent with standard clinical reporting practice by an experienced TB specialist, 
radiologist or a pulmonologist, who is specifically required to look for signs of active TB or 
signs of past/inactive TB -infection. The official report of the imaging must specifically indicate 
the absence of findings suggestive of current active TB or prior inactive TB. In addition to a 
physical examination done intermittently throughout the study, subjects will be evaluated at 
Screening, Baseline, and every 12 weeks thereafter, including the Week 96/WD Visit, for signs 
and symptoms of latent or active TB infection and risk factors for exposure to TB using the TB 
questionnaire.
Change #14
5.1.1
Part A, paragraph 1
Period 1 (Screening Period): Up to 5 Weeks before Baseline
Eligible subjects will be informed about the study and sign the informed consent. Concomitant 
medications such as MTX, SSZ, hydroxychloroquine (HCQ), NSAIDs, and corticosteroids, will 
be verified and, if required, the washout of any medications not permitted for use during the 
study will be started. Concomitant medications must follow the protocol requirements in 
Table 6.1. Subjects will receive a physical examination. Women of childbearing age will be 
tested for pregnancy. Laboratory data (hematology, urine, and biochemistry tests) and a fecal 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 114 of 173
stool sample will be obtained, and treatment of latent TB (LTB), where necessary, initiated. 
Subjects must undergo a TB test and complete a TB questionnaire. Bath Ankylosing Spondylitis 
Disease Activity Index, BASMI, and spinal mobility assessments will be performed. 
Additionally, a central reading of the x-ray will define the stratification of the subjects into the 
nr-axSpA or the AS subpopulation. 
Has been changed to:
Period 1 (Screening Period): Up to 5 Weeks before Baseline
Eligible subjects will be informed about the study and sign the informed consent. Concomitant 
medications such as MTX, SSZ, hydroxychloroquine (HCQ), NSAIDs, and corticosteroids, will 
be verified and, if required, the washout of any medications not permitted for use during the 
study will be started. Concomitant medications must follow the protocol requirements in Table 
6.1. Subjects will receive a physical examination and vital signs measurements will be taken. 
Women of childbearing age will be tested for pregnancy. Laboratory data (hematology, urine, 
and biochemistry tests) and treatment of latent TB (LTB), where necessary, will be collected. 
Subjects must undergo a TB test and complete a TB questionnaire. Patient’s Global Assessment 
of Disease Activity, BASDAI, BASMI, spinal mobility assessments, and MRI will be performed. 
Additionally, a central reading of the x-ray will define the stratification of the subjects into the 
nr-axSpA or the AS subpopulation. 
Change #15
5.1.2
Part B, period 3, last paragraph
Stool samples for fecal calprotectin will be collected for all subjects at Weeks 48 and 
96/withdrawal.
Has been changed to:
Stool samples for fecal calprotectin will be collected for all subjects at Weeks 48 and 96/WD and 
blood samples for serum calprotectin will be collected for all subjects 3 to 5 days prior to 
Week 48, Week 72, and at Week 96/WD.
Change #16
5.1.3 Escape treatment, first paragraph
The interactive voice or web response system (IXRS) will be used to determine whether escape 
criteria are met.
Has been changed to:
The interactive voice or web response system (IXRS) will be used to determine whether flare 
criteria are met.
Change #17
5.1.4
Study duration per subject 
For each subject, the study will last a maximum of 109 weeks, as follows:

Up to 5 weeks of Screening Period

48 weeks in the Open-Label Period
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 115 of 173

48 weeks in the Double-Blind Period (dose reduction/withdrawal of CZP-treatment) 

A SFU Visit 10 weeks after last dose administration (Period 4)
For subjects who experience a flare during the Double-Blind Period, the study duration might be 
prolonged (refer to Section 6.3.2).
The end of the study is defined as the date of the last visit of the last subject in the study.
Has been changed to:
For each subject, the study will last a maximum of 109 weeks, as follows:

Up to 5 weeks of Screening Period

48 weeks in the Open-Label Period

48 weeks in the Double-Blind Period (dose reduction/withdrawal of CZP-treatment) 

A SFU Visit 10 weeks after last dose administration (Period 4)
Of the 10 weeks interval specified for the SFU Visit, the first 2 weeks coincide with the last 
2 weeks of the Double-Blind Period (ie, last 2 weeks of the 48 weeks) and the last administration 
is at Week 94. Hence, the maximum duration is 109 weeks. 
For subjects who experience a flare during the Double-Blind Period, the study duration might be 
prolonged (refer to Section 6.3.2).
The end of the study is defined as the date of the last visit (SFU) of the last subject in the study.
Change #18
5.1.5 Planned number of subjects and sites 
Approximately 1250 subjects will be screened in order to enroll 750 subjects into Part A, where 
210 subjects are expected to meet the sustained remission criteria and be eligible for 
randomization into Part B. Ankylosing Spondylitis Disease Activity Score will be closely 
monitored during Part A of the study to project the percentage of enrolled subjects likely to 
achieve ASDAS-ID at the end of Part A. The enrollment will be adjusted accordingly in order to 
achieve the required number of 210 subjects in sustained clinical remission qualifying for Part B. 
The end of the study is defined as the date of the last visit (SFU) of the last subject in the study. 
It is planned to enroll the subjects at approximately 95 sites.
Has been changed to:
Approximately 1250 subjects will be screened in order to enroll 750 subjects into Part A, where 
210 subjects are expected to meet the sustained remission criteria and be eligible for 
randomization into Part B. Ankylosing Spondylitis Disease Activity Score will be closely 
monitored during Part A of the study to project the percentage of enrolled subjects likely to 
achieve sustained remission at the end of Part A. The enrollment will be adjusted accordingly in 
order to achieve the required number of 210 subjects in sustained clinical remission qualifying 
for Part B. 
It is planned to enroll subjects at approximately 95 sites.
.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 116 of 173
Change #19
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period 1 (Screening)
2 (Open-Label)
3 (Double-Blind)
4
/
(
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0
2
4
6
12
14
24
26
32
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60
62
72
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84
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46
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70
82
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Protocol Activity
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visit
Inclusion/exclusion
X
X
Informed consent b
X
Demographic data
X
Medical history (including
axSpA
X
Vital signs c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Haematology/
urine/ 
biochemistry
Xd
Xd
X
X
X
X
X
X
X
X
X
X
CRP e
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testing f
X
X
X
X
PE g
X
X
X
X
X
X
X
X
X
X
X
Extra-articular assessments
X
X
X
X
X
X
X
X
X
X
X
X
Chest x-ray h
X
TB test i
X
X
X
TB questionnaire
X
X
X
X
X
X
X
X
X
X
Sacroiliac joint x-ray j
X
MRI k
X
X
X
Stool sample l
X
X
X
IBD-Questionnaire
X
X
X
BASMI and Spinal mobility m
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 117 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period 1 (Screening)
2 (Open-Label)
3 (Double-Blind)
4
/
k (
)
-5 to -1
0
2
4
6
12
14
24
26
32
34
H
36
38
3-5
48
50
HN
52
54
60
62
72
74
84
86
96/ 
WD
SFU a
10
22
30
46
prio
58
70
82
94
H
H
H
H
r to
HN
HN
HN
HN
Protocol Activity
W48
visit
BASDAI e
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
AsQoL
X
X
X
X
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
X
X
X
X
X
MASES
X
X
X
X
X
X
X
X
X
Total and
nocturnal 
spinal pain
X
X
X
X
X
X
X
X
X
X
X
X
Swollen and tender joint counts
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of Disease
Activity e
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigator’s AS assessment
X
X
X
X
X
X
X
X
X
X
Work Productivity Survey
X
X
X
X
X
X
X
X
X
X
Resources utilization n
X
X
X
X
X
X
X
X
X
CZP plasma
concentration/ anti-
CZP Abs / Biomarker
X
X
X
X
X
X
X
X
X
X
Genetics/genomics/ proteomics
o
X
X
X
X
X
X
Prior and Concomitant
medication p
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Y
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O Y
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 118 of 173
AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IXRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc on-site
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc self-inj. at home
X
X
X
X
X
Randomization
X
Nurse visit at subj. home (incl. 
study drug sc inj.) q
X
X
X
X
X
Check of sustained remission 
criteria r
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone Contact s
X
X
X
X
Abs=antibodies; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing Spondylitis Quality of Life; axSpA=axial spondyloarthritis; 
BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis 
Metrology Index; CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site visit; HIV=human 
immunodeficiency virus; HLA-B27=human leukocyte antigen B27; HN=home nurse visit at subjects home; IBD=Inflammatory bowel disease; incl.=including; 
inj=injection; IXRS=Interactive Voice or Web Response System; MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; MRI=magnetic resonance 
imaging; PE=physical exam; sc=subcutaneously; SF-36=Short‑Form 36‑item Health Survey; SFU=Safety Follow-Up; SI=sacroiliac; subj=subject; 
TB=tuberculosis; W=Week; WD=Withdrawal; WHO=World Health Organization
a SFU: 10 weeks after last dose of study medication.
b Informed consent: Prior to any study activities, subjects will be asked to read and sign the informed consent form for the conduct of the study. A separate 
informed consent form will be obtained from subjects consenting also to the use of their blood samples for possible genetic, genomic, and proteomic analysis.
c Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening and Baseline, thereafter pulse rate, systolic 
and diastolic blood pressures and temperature are to be measured. If a subject experiences an AE, respiration rate will be measured in addition. 
d Testing to rule out hepatitis B surface antigen, antibodies to hepatitis C, and antibodies at Screening only. Testing for HLA-B27 at Baseline only.
e To be assessed as indicated and from Week 52 onwards every 4 weeks only
f Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and SFU and urine testing at Baseline and Week 96/WD 
Visit.
g Includes evaluation of signs and symptoms of active TB and risk factors for exposure to TB. Weight is to be measured at Screening, Baseline, Week 48, and at 
Completion at Week 96/Withdrawal. Height will be measured at the Baseline Visit only.
h Screening chest x-ray must have occurred within 3 months prior to Screening Visit and should be repeated only if the TB test was confirmed positive or any 
further evidence is suggestive of potential TB infection (eg, exposure).
i QuantiFERON TB GOLD test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB GOLD test is not locally available. The TB tests 
will be repeated at Week 48 and 96 (or at Early Withdrawal Visit if medically indicated) for subjects with previously negative TB test result.
j Sacroiliac joint x-rays will be performed at Screening and used as the Baseline assessment for all subjects. An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit may be used as the Baseline assessment provided that the film can be submitted and meets the requirements for central reading.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 119 of 173
k Magnetic resonance imaging of the spine and sacroiliac joints to be performed at Screening, Week 48, and 96 or Early WD Visit if MRI was performed more 
than 12 weeks prior to Early WD Visit.
l Kit for collection of stool sample to be provided at Screening Visit. Stool sample shall be obtained prior to Baseline and provided to the Investigator at the 
Baseline Visit.
m Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal flexion, cervical rotation, tragus to wall distance, 
and maximal intermalleolar distance.
n Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by the protocol, hospitalizations/emergency 
room visits.
o Blood sample for genetic analysis at Baseline only, for genomic and proteomic analysis at all indicated timepoints.
p Prior medication will be at Screening only.
q Nurse visit at home only where approved and with agreement of subjects. Otherwise, the visit procedures will be done on-site by the site-staff.
r Refer to Protocol Section 3 for definition. In case of loss of sustained remission in Part B, the subject must visit the study site for the next scheduled dose of 
study medication. The Investigator will initiate the escape treatment as appropriate. Refer to Table 5.2 for details.
s Subjects will be contacted by telephone about every 4 weeks in between the on-site visits.
REDACTED COPY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 120 of 173
Has been changed to
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Inclusion/exclusion
X
X
Informed consent c
X
Demographic data
X
Medical history 
(including axSpA and 
extra-articular 
manifestations history)
X
Vital signs d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology/urine/
biochemistry
Xe
X
X
X
X
X
X
X
X
X
X
X
CRP f
X 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testing g
X
X
X
X
PE h
X
X
X
X
X
X
X
X
X
X
X
Extra-articular 
assessments
X
X
X
X
X
X
X
X
X
X
X
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 121 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Chest x-ray i
X
TB test j
X
X
X
TB questionnaire
X
X
X
X
X
X
X
X
X
X
Sacroiliac joint x-ray k
X
MRI l
X
X
X
Stool sample m
X
X
X
Serum calprotectin
X
X
X
X
X
X
IBD-Questionnaire
X
X
X
BASMI and Spinal 
mobility n
X
X
X
X
X
X
X
X
X
X
X
X
X
BASDAI f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
AsQoL
X
X
X
X
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
X
X
X
X
X
EDACTED COPY
COPY
COPY
PY 
COPY
TED
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any marketing authorization application and any extensions or variations thereof. 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 122 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
MASES
X
X
X
X
X
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
X
X
X
X
X
X
X
X
Swollen and tender joint 
counts
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of Disease 
Activity f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of Disease 
Activity
X
X
X
X
X
X
X
X
X
X
Work Productivity Survey
X
X
X
X
X
X
X
X
X
X
Resources utilization o
X
X
X
X
X
X
X
X
X
CZP plasma 
concentration/ 
ADAb 
X
X
X
X
X
X
X
X
X
X
Biomarker
X
X
X
X
X
X
X
X
X
X
Genetics
X
X
EDACTED COPY 
OPY
OPY
PY
TED
TE
X
C
X
COP
OP
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RE
RE
X
DA
X
ACTE
TE
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t cannot be used to support any marketing authorization application and any extensions or variations thereof. 
2
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or 
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This document canno
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 123 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Genomics/ proteomics 
X
X
X
X
X
X
Prior and Concomitant 
medicationp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IXRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc self-inj. at 
home
X
X
X
X
X
Randomization
X
Nurse visit at subj. home 
(incl. study drug sc inj.) q
X
X
X
X
X
Check of sustained 
remission criteria r
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone Contact s
X
X
X
X
Abs=antibodies; ADAb= anti-CZP antibody concentration; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing Spondylitis Quality of Life; 
axSpA=axial spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; 
BASMI=Bath Ankylosing Spondylitis Metrology Index; CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; 
H=home, no site visit; HIV=human immunodeficiency virus; HLA-B27=human leukocyte antigen B27; HN=home nurse visit at subject’s home; 
IBD=Inflammatory bowel disease; incl.=including; inj=injection; IXRS=Interactive Voice or Web Response System; MASES=Maastricht Ankylosis Spondylitis 
REDACTED COPY 
OPY
OPY
PY
D COP
COP
D CO
ACTED
CTE
X
D
X
ED
ED
ED
AC ED
RE
RE
X
DA
X
AC
AC
AC
AC
EDAC
RE
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X
R
X
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support any marketing authorization application and any extensions or variations thereof. 
2
on
PART
or 
PART
va
3 (Doub
sio
3 (Doub
s o
and any extx
ex
o 
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58
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HN
60
ten
60
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 124 of 173
Enthesitis Score; MRI=magnetic resonance imaging; PE=physical exam; sc=subcutaneously; SF-36=Short‑Form 36‑item Health Survey; SFU=Safety Follow-
Up; SI=sacroiliac; subj=subject; TB=tuberculosis; W=Week; WD=Withdrawal; WHO=World Health Organization
a Assessments conducted 3 to 5 days prior to Week 48 will serve as the qualification assessments for subjects determined to be eligible for randomization into 
Part B at Week 48.
b SFU: 10 weeks after last dose of study medication.
c Informed consent: Prior to any study activities, subjects will be asked to read and sign the informed consent form for the conduct of the study. A separate 
informed consent form will be obtained from subjects consenting also to the use of their blood samples for possible genetic, genomic, and proteomic analysis.
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening and Baseline, thereafter pulse rate, systolic 
and diastolic blood pressures and temperature are to be measured. If a subject experiences an AE, respiration rate will be measured in addition. 
e Testing to rule out hepatitis B surface antigen, antibodies to hepatitis C, antibodies to HIV and HLA-B27 at Screening only.
f To be assessed as indicated and from Week 52 onwards every 4 weeks only.
g Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and SFU and urine testing at Baseline and Week 96/WD 
Visit.
h Includes evaluation of signs and symptoms of active TB and risk factors for exposure to TB. Weight is to be measured at Screening, Baseline, Week 48, and at 
Week 96/WD. Height will be measured at the Baseline Visit only.
i Screening chest x-ray must have occurred within 3 months prior to Screening Visit and should be repeated only if the TB test was confirmed positive or any 
further evidence is suggestive of potential TB infection (eg, exposure).
j QuantiFERON TB GOLD test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB GOLD test is not locally available. The TB test 
will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for subjects with previously negative TB test result.
k Sacroiliac joint x-rays will be performed at Screening and used as the Baseline assessment for all subjects. An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit may be used as the Baseline assessment provided that the film can be submitted and meets the requirements for central reading.
l Magnetic resonance imaging of the spine and sacroiliac joints to be performed at Screening, Week 48, and 96 or WD Visit if MRI was performed more than 
12 weeks prior to WD Visit.
m Kit for collection of stool sample to be provided at Screening Visit. Stool sample shall be obtained prior to Baseline and provided to the Investigator at the 
Baseline Visit.
n Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal flexion, cervical rotation, tragus to wall distance, 
and maximal intermalleolar distance.
o Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by the protocol, hospitalizations/emergency 
room visits.
p Prior medication will be at Screening only.
q Nurse visit at home only where approved and with agreement of subjects. Otherwise, the visit procedures will be done onsite by the site staff.
r Refer to Protocol Section 3 for definition. In case of loss of sustained remission in Part B, the subject must visit the study site for the next scheduled dose of 
study medication. The Investigator will initiate the escape treatment as appropriate. Refer to Table 5.2 for details.
s Subjects will be contacted by telephone about every 4 weeks in between the onsite visits.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 125 of 173
Change #20
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare in 
Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6
to 10
H/H N 
a
12 (and
every 12 weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Vital signs d
X
X
X
X
Haematology/ urine/ biochemistry
X
X
CRP e
X
X
X
X f
X
X f
Stool sample g
X
X
IBD-Questionnaire g
X
X
PE
X
X
X
X
Extra-articular assessments
X
X
X
MRI h
X
X
TB questionnaire
X
X
BASMI & Spinal mobility i
X
X
X
X
BASDAI
X
X
X
X f
X
X f
BASFI
X
X
X
X
SF-36
X
X
X
AsQoL
X
X
X
X
EQ-5D
X
X
X
MASES
X
X
X
X
Total and nocturnal spinal pain
X
X
X
X
Patient’s Global Assessment of Disease Activity
X
X
X
X f
X
X f
Investigator’s AS assessment
X
X
X
X
TED COPY 
X
Y
X
Y
X
OPY
X
PY
O Y
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 126 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
P
t B f
bj
t
i
i
fl
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6
to 
10
/
12 (and
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Work Productivity Survey
X
X
X
Resources utilization j
X
X
X
CZP plasma concentration/anti-CZP Abs / Biomarker
X
X
X
X
Concomitant medication
X
X
X
X
AEs
X
X
X
X
IXRS
X
X
X
X
X
X
Study drug sc on-site
X
X
X
X
Study drug sc self-inj. at home
X
X
Telephone Contact k
X
X
Has been changed to:
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
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X
X
X
X
Hematology/urine/ biochemistry
X
X
CRP e
X
X
X
X f
X
X f
Stool sample g
X
X
Serum calprotectin g
X
X
IBD-Questionnaire g
X
X
D COPY
X
PY 
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 127 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
PE 
X
X
X
X
Extra-articular assessments
X
X
X
MRI h
X
X
TB questionnaire
X
X
BASMI & Spinal mobility i
X
X
X
X
BASDAI
X
X
X
X f
X
X f
BASFI
X
X
X
X
SF-36
X
X
X
AsQoL
X
X
X
X
EQ-5D
X
X
X
MASES
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
Patient’s Global Assessment of Disease Activity
X
X
X
X f
X
X f
Physician’s Global Assessment of Disease Activity
X
X
X
X
Work Productivity Survey
X
X
X
Resources utilization j
X
X
X
CZP plasma concentration/ADAb
X
X
X
X
Biomarker
X
X
X
X
Concomitant medication
X
X
X
X
EDACTED COPY 
Y
X
OPY
X
Y
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 128 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
AEs
X
X
X
X
IXRS
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
Study drug sc self-inj. at home
X
X
Telephone Contact k
X
X
Change #21
Section 6.1 Inclusion criteria
Criterion #6 (sub-bullet #3)

Spinal pain >4 on a 0 to 10 NRS (from BASDAI Item 2)
Has been changed to:

Spinal pain ≥4 on a 0 to 10 NRS (from BASDAI Item 2)
Change #22
6.2 Exclusion criteria 
Criterion #8
Table 6.1 Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
Study Visits
Analgesics (including, but
not limited to
acetaminophen,
paracetamol, opiates, or
combinationsthereof)
Up to maximum approved
dose
Any change in stable dose
regimen is excluded in
the 14 days prior to the
Baseline Visit.
Any ad hoc (prn) use of
analgesics is not
permitted within 24 hours
prior to any postscreening
visit.
Stable dose of analgesics
(including narcotics) are
permitted
throughout
the study.
REDACTED COPY 
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NRS (f
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 129 of 173
NSAIDs(including
cyclooxygenase 2
[COX 2] inhibitors)
Up to maximum approved
dose regimen
Any change in stable dose
regimen is excluded in
the 14 days prior to the
Baseline Visit.
Any ad hoc (prn) use of
NSAIDs is not permitted
within 24 hours prior to
any postscreening visit.
NSAID dose should be
stable until Week 96 (if
subjects have to decrease
or stop taking medication
due to safety reasons,
they may reduce their
dose and continue in the
study).
SAARDsb:
SSZ and/or HCQ and/or
MTX and/or LFN and /or
AZA
Maximum allowed: SSZ
≤3g daily
HCQ ≤400mg daily
MTX ≤25mg weekly
AZA ≤150mg/day
LFN ≤20mg/day (see
exclusion criteria for
washoutrequirements)
SAARD use initiated and
or any change in the dose
regimen in the 28 days
prior to the Baseline Visit.
No change is permitted in
the route of
administration for MTX
(im, sc, or oral) in the 28
days prior to the Baseline
Visit
Use of LFN in the 6
months prior to the
Baseline Visit unless a
cholestyraminewashout
has been performed. In
case of a cholestyramine
washout, use 28 days
prior to the Baseline Visit
SAARDs should be stable
until Week 96 (if a subject
has to decrease or stop
taking medications due to
safety reasons, they may
reduce their SAARDs and
continue in the study).
Has been changed to:
Drug class
Dose
Exclusion criteria
Study Visits
Analgesics (including, but 
not limited to 
acetaminophen, 
paracetamol, opiates, or 
combinations thereof)
Up to maximum approved 
dose 
Any change in stable dose 
regimen is excluded in the 
14 days prior to the 
Baseline Visit.
Any ad hoc (prn) use of 
analgesics is not permitted 
within 24 hours prior to 
any postscreening visit.
Stable dose of analgesics 
(including narcotics) are 
permitted throughout the 
study.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 130 of 173
Drug class
Dose
Exclusion criteria
Study Visits
NSAIDs (including 
cyclooxygenase 2 
[COX 2] inhibitors) 
Up to maximum approved 
dose regimen 
Any change in stable dose 
regimen is excluded in the 
14 days prior to the 
Baseline Visit.
Any ad hoc (prn) use of 
NSAIDs is not permitted 
within 24 hours prior to 
any postscreening visit.
NSAID dose can be 
down-titrated at 
Investigator discretion, if 
clinically indicated, until 
Week 28, after which 
NSAID treatment should 
remain as stable as 
possible.
NSAID dose should be 
stable until Week 96 (if 
subjects have to decrease 
or stop taking medication 
due to safety reasons, they 
may reduce their dose and 
continue in the study).
SAARDsb:
SSZ and/or HCQ and/or 
MTX and/or LFN and /or 
AZA
Maximum allowed:
SSZ ≤3g daily
HCQ ≤400mg daily 
MTX ≤25mg weekly
AZA ≤150mg/day
LFN ≤20mg/day
SAARD use initiated 
and/or any change in the 
dose regimen in the 28 
days prior to the Baseline 
Visit. 
No change is permitted in 
the route of administration 
for MTX (im, sc, or oral) 
in the 28 days prior to the 
Baseline Visit
SAARDs should be stable 
until Week 96 (if a subject 
has to decrease or stop 
taking medications due to 
safety reasons, they may 
reduce their SAARDs and 
continue in the study).
Change #23
6.2 Exclusion Criteria
13 Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 3 months following the last dose of the investigational product.
Has been changed to:
13 Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 10 weeks (or – for participating countries of the EU – 5 months in accordance 
with the SmPC) following the last dose of the investigational product.
Change #24
6.3.2
Escape criteria, paragraphs 2, 3, and 4
Subjects escaping from placebo to full-dose CZP (200mg Q2W) will receive a loading dose of 
CZP (400mg Q2W) at the 3 consecutive visits after the flare. Subjects escaping from half-dose 
CZP to full-dose CZP will receive CZP 200mg Q2W at the 3 consecutive visits after the flare. In 
REDACTED COPY
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6.

UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 131 of 173
order to maintain the blind, subjects escaping from half-dose CZP to full-dose CZP will receive a 
placebo administration and a CZP 200mg administration at these 3 visits. 
Subjects randomized to the CZP full-dose (200mg Q2W) treatment during the Double-Blind 
Period who qualify for escape will remain on their current treatment allocation. As with subjects 
escaping from half-dose CZP to full-dose CZP, these subjects will receive a placebo and CZP 
200mg injection at the 3 visits after the flare in order to maintain the blind to the randomized 
treatment. 
After the loading dose, all escaped subjects will continue full-dose CZP treatment in an open-
label fashion.
Has been changed to:
6.3.2
Escape treatment
Subjects escaping from placebo to full-dose CZP (200mg Q2W) will receive a loading dose of 
CZP (400mg Q2W; 2 injections) at the 3 consecutive visits after the flare. Subjects escaping 
from half-dose CZP to full-dose CZP will receive a loading dose of CZP 200mg Q2W at the 3 
consecutive visits after the flare. In order to maintain the blind, subjects escaping from half-dose 
CZP to full-dose CZP will receive a placebo administration and a CZP 200mg administration (a 
total of 2 injections) at these 3 visits (Figure 7.1). 
Subjects randomized to the CZP full-dose (200mg Q2W) treatment during the Double-Blind 
Period who qualify for escape will remain on their current treatment allocation. As with subjects 
escaping from half-dose CZP to full-dose CZP, these subjects will receive a placebo and 
CZP 200mg injection (a total of 2 injections) at the 3 visits after the flare in order to maintain the 
blind to the randomized treatment. 
After the loading dose (200mg Q2W or 400mg Q2W), all escaped subjects will continue full-
dose CZP treatment in an open-label fashion.
Change #25
7.2.1
Treatment administration, paragraphs 2 and 3
Study medication will be given sc by dedicated and adequately trained site personnel. Suitable 
areas for administrations are the lateral abdominal wall and upper outer thigh. During each 
dosing visit, if 2 injections are being administered (ie, CZP 400mg as 2 injections of 200mg 
each) each of the 2 injections should be administered at a separate injection site.
Has been changed to:
Study medication will be given sc by dedicated and adequately trained site personnel or the 
subject may start self-administering from Week 6 after training at Week 2 and Week 4.
Suitable areas for administrations are the lateral abdominal wall and upper outer thigh. During 
each dosing visit, if 2 injections are being administered (ie, loading dose CZP 400mg as 
2 injections of 200mg each) each of the 2 injections should be administered at a separate 
injection site.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 132 of 173
Change #26
7.3 Packaging
Part A
Each site will receive during Period 2 (Open-Label Period: Week 0 [Baseline] to Week 47) 
uniquely numbered PFSs of CZP, which will be packaged in individual labeled protective 
containers (clamshells).
Part B
Each site will receive during Period 3 (Double-Blind Period: Week 48 to Week 96, placebo 
controlled) uniquely numbered PFSs of CZP or placebo, which will be packaged in individual 
labeled protective containers (clamshells).
Has been changed to:
For Part A and B, CZP and placebo are packaged and labeled according to Good Manufacturing 
Practice guidelines and applicable laws or regulations. They are suitably packaged in such a way 
as to protect the IMP from deterioration during transport and storage.
Change #27
7.8.1
Permitted concomitant treatments (medications and therapies)
The following concomitant medications/treatments are permitted during the study, from Baseline 
onward, with restrictions as specified: 

NSAIDs/cyclooxygenase 2 (COX-2) inhibitors: doses should be stable throughout the study 
and ad hoc as needed (prn) inhibitors should not be used 24 hours prior to any post-Screening 
study visit. No change in dose or dose regimen is allowed during the study except for reasons 
of safety, where the NSAIDs/COX-2 inhibitors dose may be decreased or discontinued.
Has been changed to:

NSAIDs/cyclooxygenase 2 (COX-2) inhibitors: doses should be stable throughout the study 
and ad hoc as needed (prn) inhibitors should not be used 24 hours prior to any post-Screening 
study visit. No change in dose or dose regimen is allowed during the study except for reasons 
of safety, where the NSAIDs/COX-2 inhibitors dose may be decreased or discontinued. 
NSAID dose may be down-titrated at Investigator discretion. The reduction in NSAID dose if 
clinically indicated is permitted at the discretion of the Investigator until Week 28, however 
after that timepoint the NSAID treatment should remain stable as much as possible.
Change #28
7.8.3
Rescue Medication
Escape medication is as described in Section 5.1.3.
Has been changed to:
Escape treatment is as described in Section 5.1.3.
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 133 of 173
Change #29
7.10
Randomization and numbering of subjects
To enroll a subject (Week 0 [Baseline]), the Investigator or designee will contact the IXRS and 
provide brief details about the subject to be enrolled. Each subject will receive a 5-digit number 
assigned at screening that serves as the subject identifier throughout the study. The subject 
number will be required in all communication between the Investigator or designee and the IXRS
regarding a particular subject. Subject numbers and kit numbers will be tracked via the IXRS.
Randomization will be stratified on:

Geographic region

mNY classification
Has been changed to:
To enroll a subject (Screening), the Investigator or designee will contact the IXRS and provide 
brief details about the subject to be enrolled. Each subject will receive a 5-digit number assigned 
at screening that serves as the subject identifier throughout the study. The subject number will be 
required in all communication between the Investigator or designee and the IXRS regarding a 
particular subject. Subject numbers and kit numbers will be tracked via the IXRS.
Randomization will be stratified on:

Geographic region (North America, Western Europe, Eastern Europe, and Asia)

mNY classification
Change #30
8.1 Screening Visit has been changed to Screening Visit (up to 5 weeks)
Modified bullets #4, 7, and 8

Washout of excluded medications
Hematology, biochemistry, and urine for clinical laboratory values (includes a serum 
pregnancy test for women of childbearing potential, and testing to rule out hepatitis B surface 
antigen, antibodies to hepatitis C, antibodies to HIV, and CRP) 
Physical examination (including weight, height, evaluation of signs and symptoms of active 
TB and risk factors for exposure to TB) and extra-articular assessment
Has been changed to:

Washout of prohibited medications
Hematology, biochemistry, and urine for clinical laboratory values (includes a serum 
pregnancy test for women of childbearing potential, HLA-B27 and testing to rule out hepatitis 
B surface antigen, antibodies to hepatitis C, antibodies to HIV, and CRP) 
Physical examination (including weight, evaluation of signs and symptoms of active TB and 
risk factors for exposure to TB) and extra-articular assessment
Inserted bullet #16 and 18
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 134 of 173

PtGADA

Fecal sample kit provided to the subject
Deleted bullet #17

AEs
Change #31
8.2 Baseline Visit (Week 0)

Blood samples will be collected for hematology, biochemistry analyses (including 
HLA-B27), CRP

Investigator’s AS assessments (PhGADA)

Plasma sample for CZP concentration, anti-CZP antibodies; and biomarkers
Has been changed to:

Blood samples will be collected for hematology, biochemistry analyses, serum calprotectin,
and CRP 

PhGADA

Plasma sample for CZP concentration, ADAb

Plasma sample for biomarkers, if applicable
Modified bullet #24:

Stool sample provided by the subject for fecal calprotectin evaluation
Change #32
8.3
Weeks 2 to 96/WD onsite visits section title has been modified and has been divided into 
subsections:
8.3.1
Weeks 2, 4, 12, 24, 32, 36, 48, 52, 60, 72, 84, and 96/WD (± 3 Days)
Assessments at these onsite visits include:

Vital signs: pulse rate, systolic and diastolic blood pressures, temperature will be measured 
(all visits). If a subject experiences an AE, respiration rate will be measured in addition. 

Blood samples will be collected for hematology and biochemistry analyses (at Weeks 12, 24, 
32, 36, 60, 72, 84, and at Week 96/WD), and CRP (at Weeks 2, 4, 12, 24, 32, 36, and from 
Week 52 onwards every 4 weeks only).

Urine pregnancy testing for women of childbearing potential will be at Week 96/WD only.

Urine will be collected for urinalysis (at Weeks 12, 24, 32, 36, 48, 60, 72, 84, and at 
Week 96/WD). 

Physical examination (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD), including 
weight at Week 48 and at Week 96/WD.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 135 of 173

Extra-articular assessments (at Weeks 4, 12, 24, 36, 48, 52, 60, 72, 84, and at Week 96/WD).

TB test (at Week 48 and at Week 96/WD only).

TB questionnaire (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD).

MRI (at Week 48 and at Week 96/WD only). 

BASMI and spinal mobility (at Weeks 2, 4, 12, 24, 36, 48, 52, 60, 72, 84, and at 
Week 96/WD only).

BASDAI (at Weeks 2, 4, 12, 24, 32, 36, 52, 60, 72, 84, and at Week 96/WD).

BASFI (at Weeks 2, 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

SF-36 (at Weeks 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

ASQoL (at Weeks 2, 4, 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

EQ-5D (at Weeks 12, 24, 36, 60, 72, 84, and at Week 96/WD only).

IBD-Q (at Week 96/WD only).

MASES (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Total spinal pain NRS and nocturnal spinal pain NRS (at Weeks 2, 4, 12, 24, 36, 52, 60, 72, 
84, and at Week 96/WD only).

Swollen and tender joint counts (at Weeks 2, 4, 12, 24, 36, 48, 52, 60, 72, 84, and at 
Completion at Week 96/WD only).

PtGADA (at Weeks 2, 4, 12, 24, 32, 36, and from Week 52 onwards every 4 weeks only).

PhGADA (at Weeks 12, 24, 36, 48, 52, 60, 72, 84, and at Week 96/WD only).

WPS (at Weeks 4, 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Resource utilization (at Weeks 12, 24, 36, 48, 60, 72, 84, and at Week 96/WD only).

Plasma for CZP concentration and ADAb (at Weeks 4, 12, 24, 60, 72, 84, and at 
Week 96/WD only).

Plasma for biomarkers (at Weeks 4, 12, 24, 60, 72, 84, and at Week 96/WD only), if 
applicable.

Genomics and proteomics (at Weeks 12, 24, 72, and at Week 96/WD only), if applicable.

Stool sample will be collected for fecal calprotectin at Week 48 and at Week 96/WD only.

Blood sample will be collected for serum calprotectin at Week 12, Week 24, Week 72 and 
Week 96/WD only.

Concomitant medication

AEs

Contact IXRS to obtain next kit numbers 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 136 of 173

Study drug administration (after all other visit assessments are completed and laboratory 
samples are drawn) (all visits at Week 96/WD).

Randomization at Week 48.

Check of sustained remission criteria (all visits except Weeks 2, 4, and Week 96/WD visit).
8.3.2
3 to 5 days prior to Week 48.

Blood samples will be collected for hematology and biochemistry analyses and CRP

BASDAI

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
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
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
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
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
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
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
Genetics
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Blood sample will be collected for serum calprotectin

AEs
Change #33
18.4 
Weeks 6 to 94 home visits and home nurse visits section title has been modified and has 
been divided into subsections:
8.4.1
Home visits during Part A
Assessments at these home visits include:

Study drug self-administration at home (at Weeks 6, 8, 10, 14, 16, 18, 20, 22, 26, 28, 30, 34, 
38, 40, 42, 44, and 46)

Subjects will be contacted by telephone in between the onsite visits (at Weeks 6 to 10, 14 to 
22, 26 to 30, and 38 to 46)
8.4.2
Home and home nurse visits during Part B
Assessments at these home and nurse visits include:

Vital signs: pulse rate, systolic and diastolic blood pressures, temperature will be measured. 
If a subject experiences an AE, respiration rate will be measured in addition (at Week 50, 
Weeks 54 to 58, 62 to 70, 74 to 82, and 86 to 94 only)
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 137 of 173

CRP and PtGADA (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)

BASDAI (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)

Contact IXRS to report kit number (all Visit at Weeks 50, 54 to 58, 62 to 70, 74 to 82, and 86 
to 94) 

Nurse visit at subject home including to perform study medication administration (at Weeks 
50, 54, 56, 58, 62, 64, 66, 68, 70, 74, 76, 78, 80, 82, 86, 88, 90, 92, and 94)

Check of sustained remission criteria (at Weeks 50, 56, 64, 68, 76, 80, 88, and 92)
Change #34
8.5 Study procedures after flare until the final assessment visit at Week 96/WD

Stool sample will be collected for fecal calprotectin at Escape Weeks 0 and 12

Patient’s Global Assessment of Disease Activity at Escape Weeks 0, 2, 4, and every 4 weeks 
thereafter until the final assessment visit at Week 96/WD

Investigator’s AS Assessment at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter 
until the final assessment visit at Week 96/WD

Plasma for CZP concentration, anti CZP antibodies, and biomarkers at Escape Weeks 0, 2, 4, 12, and 
every 12 weeks thereafter until the final assessment visit at Week 96/WD
Has been changed to:

Stool sample will be collected for fecal calprotectin and blood sample for serum calprotectin 
at Escape Weeks 0 and 12

PtGADA at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final 
assessment visit at Week 96/WD

PhGADA at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the final 
assessment visit at Week 96/WD

Plasma for CZP concentration and ADAb at Escape Weeks 0, 2, 4, 12, and every 12 weeks 
thereafter until the final assessment visit at Week 96/WD

Plasma for biomarkers at Escape Weeks 0, 2, 4, 12, and every 12 weeks thereafter until the 
final assessment visit at Week 96/WD, if applicable
Change #35
8.6 Safety Follow Up Visit

Plasma for CZP concentration, anti-CZP antibodies, and biomarkers
Has been changed to:

Plasma for CZP concentration and ADAb

Plasma for biomarkers 
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24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 138 of 173
Change #36
9.1.1. ASAS20, ASAS40, ASAS 5/6 response, and ASAS partial remission
The ASAS20 is defined as an improvement of at least 20% and absolute improvement of at least 
1 unit on a 0 to 10 NRS in at least 3 of the 4 following domains:

Patient's Global Assessment of Disease Activity (see Section 9.2.3)

Pain assessment (the average of total spinal pain NRS score)
Has been changed to:
The ASAS20 is defined as an improvement of at least 20% and absolute improvement of at least 
1 unit on a 0 to 10 NRS in at least 3 of the 4 following domains:

Patient's Global Assessment of Disease Activity (see Section 9.2.3)

Pain assessment (the total spinal pain NRS score)
The following sentence has been added to this section:
The ASAS assessments per visit are described in the schedule of study assessments Table 5.1. 
Change #37
9.1.7. Ankylosing spondylitis disease activity score (ASDAS)
Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
Has been changed to:
Back pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
Change #38
9.2.4 SF-36
The MCIDs for SI-36 domains and component summaries are 5 and 2.5 points respectively 
(Strand et al, 2005). 
Has been changed to:
The MCIDs for SI-36 domains and component summaries are 2 to 4 points and 2 to 3 points 
respectively (Ware et al, 2007). 
Change #39
9.2.7. Physician’s global assessment of disease activity
This assessment by the Investigator should be made without any knowledge of the PhGADA.
Has been changed to:
This assessment by the Investigator should be made without any knowledge of the PtGADA.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 139 of 173
Change #40
9.2.9
Health status (EQ-5D)
The EQ-5D is comprised of a 5-item health status measures and a visual analog rating scale. 
Each of the 5 health states is divided into 3 levels: no problem, some or moderate problems, and 
extreme problems and is scored as 1, 2, and 3, respectively. The EQ-5D VAS records the 
respondent’s self-rated health status on a vertical 20cm scale, 0 to 100 graduated (0=worst 
imaginable health status, 100=best imaginable health status).
Has been changed to:
The EQ-5D is comprised of a 5-item health status measures and a visual analog rating scale. 
Each of the 5 health states is divided into 3 levels: no problem, some or moderate problems, and 
extreme problems and is scored as 1, 2, and 3, respectively. The scored levels for 5 dimensions 
can be combined in a 5-digit number describing the respondent’s health profile or can be 
converted into a single summary index. The published mean Minimally Important Difference 
(MID) for the index value is 0.074 (range -0.011 to 0.140) and the SRM of 0.24 (range -0.05 to 
0.43) (Walters et al, 2005). The EQ-5D VAS records the respondent’s self-rated health status on 
a vertical 20cm scale, 0 to 100 graduated (0=worst imaginable health status, 100=best 
imaginable health status). The MID for VAS of 7 in cancer patients was published in 2007 by 
Pickard et al. (Pickard et al, 2007).
Change #41
9.2.12 Fecal calprotectin
The calgranulins, S100A8/S100A9 and S100A12, are calcium-binding proteins of the S100 
family. They are released from activated monocytes and granulocytes at local sites of 
inflammation during the early phase of the immune response. Extracellularly, they exert 
important pro-inflammatory effects, thereby providing stimulation and amplification of the 
innate immune reaction. Calgranulins can be measured in serum and stool, and have been found 
to be very sensitive markers of innate immune activation. Moreover, the S100A8/S100A9 
heterodimer, also called calprotectin, has been established for a long time as a fecal marker of 
disease activity in inflammatory bowel disease (Foell et al, 2009; Foell et al, 2007).
For all subjects, fecal calprotectin will be examined for gut inflammation as described in the 
schedule of study assessments Table 5.1. Fecal calprotectin will be measured at Baseline, 
Week 48 and Week 96 for the completers. For escapers, an additional sample will be collected at 
the time when they are escaping (Week 0) and 12 weeks thereafter.
Has been changed to:
9.2.12 Fecal and serum calprotectin
The calgranulins, S100A8/S100A9 and S100A12, are calcium-binding proteins of the S100 
family. They are released from activated monocytes and granulocytes at local sites of 
inflammation during the early phase of the immune response. Extracellularly, they exert 
important pro-inflammatory effects, thereby providing stimulation and amplification of the 
innate immune reaction. Calgranulins can be measured in serum and stool, and have been found 
to be very sensitive markers of innate immune activation. Moreover, the S100A8/S100A9 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 140 of 173
heterodimer, also called calprotectin, has been established for a long time as a fecal marker of 
disease activity in inflammatory bowel disease (Foell et al, 2009; Foell et al, 2007).
For all subjects, fecal and serum calprotectin will be examined for gut inflammation as described 
in the schedule of study assessments Table 5.1. Fecal calprotectin will be measured at Baseline, 
Week 48 and Week 96 and serum calprotectin will be measured at Baseline, Week 12, Week 24, 
3 to 5 days prior to Week 48, Week 72, and Week 96for the completers. For escapers, an 
additional sample will be collected at the time when they are escaping (Week 0) and 12 weeks 
thereafter.
Change #42
9.2.13 Inflamatory Bowel Disease Questionnaire assessment 
The IBD-Q remission is defined as an IBD-Q total score ≥170 points (Irvine et al, 1994).
Has been changed to:
The IBD-Q remission is defined as an IBD-Q total score ≥170 points (Guyatt et al. 1989).
Change #43
10 Assessment of Pharmacokinetics and Pharmacogenomics Variable(s)
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline
(Week 0), and for genomic and proteomics analysis only, at Weeks 12, 24, 48, 72, and at 
Completion at Week 96/WD to enable exploratory evaluation of biomarkers relative to drug 
treatment and inflammatory and immune response processes. 
Has been changed to:
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline 
(Week 0), and for genomic and proteomics analysis only, at Weeks 12, 24, 3 to 5 days prior to 
Week 48, 72, and at Completion at Week 96/WD to enable exploratory evaluation of biomarkers 
relative to drug treatment and inflammatory and immune response processes.
Change #44
12.6
Laboratory Measurements
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline (Week 
0), Weeks 12, 24, 32, 36, 48, 60, 72, 84, 96/WD, and at the SFU Visit (10 weeks after the last 
dose). Testing for hepatitis B surface antigen and antibodies to hepatitis C and HIV will be 
performed at Screening. Screening for HLA-B27 will be performed at Baseline only.
Has been changed to:
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline
(Week 0), Weeks 12, 24, 32, 36, 3 to 5 days prior to 48, 60, 72, 84, 96/WD, and at the SFU Visit 
(10 weeks after the last dose). Testing for HLA-B27, hepatitis B surface antigen, and antibodies 
to hepatitis C and HIV will be performed at Screening.
Change #45
13.2.1 Definition of source data
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The following sentences have been added to this section:
The following data will be recorded directly in the ePRO tablet and will not appear in a source 
document as defined above:

Patient Reported Outcome questionnaires: SF-36, EQ-5D, PtGADA, BASDAI, BASFI, 
ASQoL, IBD-Questionnaire, Work Productivity Survey, Total and Nocturnal Spinal Pain 
Questionnaire
Change #46
13.3.1 Case report form completion
This study will also use an electronic device (Site Tablet) to capture the PhGADA and joint 
counts (see Section 13.3.2).
Has been changed to:
This study will also use an electronic device (Site Tablet) to capture patient reported outcomes 
(see Section 13.3.2).
Change #47
13.3.2 Electronic reporting outcome
This study will use an electronic Site Tablet having a large screen and intuitive fingertip data 
entry to ensure all questionnaire data are captured appropriately, completely, and on time. Not 
only subjects’ data will be collected with the tablets, physicians’ data (joint counts and 
PhGADA) will be entered directly.
Has been changed to:
This study will use an electronic Site Tablet having a large screen and intuitive fingertip data 
entry to ensure all questionnaire data are captured appropriately, completely, and on time. Only 
subjects’ data will be collected with the tablets. Physicians’ data (joint counts and PhGADA) 
will be entered in the eCRF or collected on worksheets.
Change #48
14.1
Definition of analysis sets
Inserted bullet #4, 5, 9, and 10

The Flared Set (FS) will consist of all subjects from the RS who experience a flare in Part B.

The Part B Full-Dose Set (FDS) will include all subjects from the RS who ever received a 
dose of CZP Q2W during Part B (including escape treatment).

The Pharmacokinetic Set A (PKSA) will consist of all subjects from the OLS who provide at 
least 1 PK sample during Part A.

The Pharmacokinetic Set B (PKSB) will consist of all subjects from the SS who provide at 
least 1 PK sample during Part B.
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Change #49
14.2
General statistical considerations
All efficacy analyses for Part B will be performed using the RS. The FAS and PPS will be used 
for a sensitivity analysis on the primary endpoint only. Efficacy summaries for variables 
collected in Part A will be based on the OLS.
The statistical analysis of the primary efficacy variable will account for the testing of multiple 
doses by using a fixed sequence testing procedure. The proportion of subjects who do not 
experience a flare (where flare is defined as ASDAS ≥2.1 on 2 consecutive visits or ASDAS 
>3.5 at any visit) will be compared between each CZP dose and placebo. The predefined order of 
hypotheses testing, each at a 2-sided 0.05 significance level for the comparison between the 
given CZP dose and placebo, will be performed in the sequence shown below:
1. CZP 200mg Q2W vs placebo
2. CZP 200mg Q4W vs placebo
The second test is performed only if the first test is significant at the 0.05 level.
A secondary objective of key importance in this study is to compare the efficacy of the full-dose 
to the half-dose. In order to evaluate this objective, a 2-sided 95% confidence interval (CI) for 
the difference in the proportion of subjects who do not experience a flare (CZP 200mg Q2W 
minus CZP 200mg Q4W) will be constructed. If the lower limit of the interval does not extend 
beyond the negative of the noninferiority margin of 15%, then noninferiority of the CZP 200mg 
Q4W dose to the CZP 200mg Q2W dose will have been established. This noninferiority test will 
be conducted only if both CZP doses are found to be statistically superior to placebo, as 
described above.
Has been changed to:
All efficacy analyses for Part B will be performed using the RS. The FAS and PPS will be used 
for a sensitivity analysis on the primary endpoint only. Efficacy summaries for variables 
collected in Part A will be based on the OLS.
Summaries at the Week 48 timepoint for laboratory data and data collected via electronic device 
(Site Tablet) will be based on the assessments conducted 3 to 5 days prior to the Week 48 clinic 
visit.
The statistical analysis of the primary efficacy variable will account for the testing of multiple 
doses by using a fixed sequence testing procedure. The proportion of subjects who do not 
experience a flare (where flare is defined as ASDAS ≥2.1 on 2 consecutive visits or ASDAS 
>3.5 at any visit) will be compared between each CZP dose and placebo. The predefined order of 
hypotheses testing, each at a 2-sided 0.05 significance level for the comparison between the 
given CZP dose and placebo, will be performed in the sequence shown below:
1. CZP 200mg Q2W vs placebo
2. CZP 200mg Q4W vs placebo
The second test is performed only if the first test is significant at the 0.05 level. 
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Change #50
14.3.2.1
Part A analysis
The percentage of subjects achieving sustained remission, ASDAS-MI, and ASDAS-CII at 
Week 48 will be summarized by treatment group using descriptive statistics (counts and 
percentages). Separate summaries will be done using NRI and observed case data.
Ankylosing Spondylitis Disease Activity Score disease activity at Week 48 will also be 
summarized by treatment group using descriptive statistics, where counts and percentages are 
reported for each of the 4 categories. Two summaries will be provided: 1 will derive disease 
activity at Week 48 using last observation carried forward (LOCF, impute using the last 
post-Baseline nonmissing result) for missing values and the other will be based on observed case 
data.
Has been changed to:
The percentage of subjects achieving sustained remission, ASDAS-MI, and ASDAS-CII at 
Week 48 will be summarized using descriptive statistics (counts and percentages). Separate 
summaries will be done using NRI and observed case data.
Ankylosing Spondylitis Disease Activity Score disease activity at Week 48 will also be 
summarized using descriptive statistics, where counts and percentages are reported for each of 
the 4 categories. Two summaries will be provided: One will derive disease activity at Week 48 
using last observation carried forward (LOCF, impute using the last post-Baseline nonmissing 
result) for missing values and the other will be based on observed case data. 
Change #51
14.3.2.2
Part B analysis
The same logistic regression model as described for the primary efficacy variable will be used to 
evaluate the noninferiority of CZP 200mg Q4W to CZP 200mg Q2W. Because the 95% CI 
resulting from the logistic regression model will be based on the odds ratio, a transformation will 
be necessary so that it can be presented in terms of a percentage difference to evaluate relative to 
the prespecified noninferiority margin of 15%. The details behind this transformation willbe 
described in the SAP. 
The time to flare will be analyzed using Kaplan-Meier methods. For those who meet the criteria 
for flare, the time will be defined as the length in days from randomization in Part B until the 
visit at which the criteria for flare were met. Subjects who discontinue the study without meeting 
the criteria for flare will be censored at the time of their last study visit. Subjects who complete 
the study without meeting the criteria for flare will be censored at their Week 96 visit. Between 
group differences will be analyzed with the log-rank statistic.
The changes from Baseline in ASDAS, BASDAI, BASFI, and BASMI at Week 96 for the FAS 
will be compared between treatment groups using a mixed model for repeated measures 
(MMRM). 
Has been changed to:
The time to flare will be analyzed using Kaplan-Meier methods. For those who meet the criteria 
for flare, the time will be defined as the length in days from randomization in Part B until the 
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visit at which the criteria for flare were met. Subjects who discontinue the study without meeting 
the criteria for flare will be censored at the time of their last study visit. Subjects who complete 
the study without meeting the criteria for flare will be censored at their Week 96 visit. Between 
group differences will be analyzed with the log-rank statistic.
The changes from Baseline in ASDAS, BASDAI, BASFI, and BASMI at Week 96 for the RS 
will be compared between treatment groups using a mixed model for repeated measures 
(MMRM). 
Change #52
14.3.2.3
Part B analysis for subjects who experience a flare
For subjects who experience a flare during Part B, the secondary efficacy variables listed below 
will be analyzed. The timepoint for these secondary efficacy analyses will be Week 96 (or later, 
if applicable, depending on when the flare occurred.
For the continuous variables (ASDAS, BASDAI, BASFI, BASMI), quantitative descriptive 
statistics by treatment group will be displayed. This summary will include the actual results at 
Week 96 (or later), change from Baseline (Week 0), change from randomization Baseline 
(Week 48), and change from the visit in which the flare occurred.
All Part B summaries after subjects experience a flare will be based on observed case data and 
will use the RS.
Has been changed to:
For subjects who experience a flare during Part B, the secondary efficacy variables listed below 
will be analyzed. The timepoint for these secondary efficacy analyses will be at Escape 
Week 12).
For the continuous variables (ASDAS, BASDAI, BASFI, BASMI), quantitative descriptive 
statistics by treatment group will be displayed. This summary will include the actual results at 
Escape Week 12, change from Baseline (Week 0), change from randomization Baseline 
(Week 48), and change from the visit in which the flare occurred. 
All Part B summaries after subjects experience a flare will be based on observed case data and 
will use the FS.
Change #53
14.3.3 Other efficacy analyses
14.3.3.1
Part A
The other efficacy variables for Part A as outlined in Section 4.1.3.1 will be summarized by visit 
and treatment group using descriptive statistics for the timepoint itself and for the change from 
Baseline. This will be done for the OLS using observed case data and with imputation using 
LOCF.
14.3.3.2
Part B
Treatment group comparisons for both CZP groups vs placebo will be performed based on the 
change from Baseline in other selected efficacy variables. These analyses will be performed 
using an ANCOVA model with variables of Baseline score, treatment group, region, and mNY 
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Page 145 of 173
criteria (yes/no) in the model. The treatment differences and corresponding 95% CIs will be 
calculated based on the adjusted means. Missing values will be imputed using LOCF. This 
analysis approach will be used for the following variables:

Total and nocturnal spinal pain

PtGADA

BASFI

Morning stiffness (BASDAI 5 and 6)

SF-36 PCS, MCS, and physical function domain

Fatigue NRS

ASQoL
Such analyses will also be done for the following continuous variables: ASDAS, BASDAI, 
BASFI, and BASMI for timepoints not specified in the secondary efficacy analyses using the 
same analysis methods described in Section 14.3.2.2. Additionally, ASDAS-MI, ASDAS-CII, 
and ASAS response variables will be analyzed using a logistic regression model similar to the 
one specified for binary response variables in Section 14.3.2.2 at timepoints not covered in the 
secondary efficacy analyses. 
Has been changed to:
14.3.3 Other efficacy analyses
14.3.3.1
Part A
The other efficacy variables for Part A as outlined in Section 4.1.3.1 will be summarized by visit 
using descriptive statistics for the timepoint itself and for the change from Baseline. This will be 
done for the OLS using observed case data and with imputation using LOCF. Further details are 
described in the SAP.
14.3.3.2
Part B analysis for subjects who experience a flare
Treatment group comparisons for both CZP groups vs placebo will be performed based on the 
change from Baseline in other selected efficacy variables. These analyses will be performed 
using an ANCOVA model with variables of Baseline score, treatment group, region, and mNY 
criteria (yes/no) in the model. The treatment differences and corresponding 95% CIs will be 
calculated based on the adjusted means. Missing values will be imputed using LOCF. This 
analysis approach will be used for the following variables:
•
Total spinal pain
•
Nocturnal spinal pain
•
PtGADA
•
Morning stiffness (BASDAI 5 and 6)
•
SF-36 PCS, MCS, and physical function domain
•
Fatigue NRS
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Page 146 of 173
•
ASQoL
Such analyses will also be done for the following continuous variables: ASDAS, BASDAI, 
BASFI, and BASMI will be analyzed using a MMRM similar to the one specified in 
Section 14.3.2.2. at timepoints not covered in the secondary efficacy analyses. Additionally, 
ASDAS-MI, ASDAS-CII, ASAS, and BASDAI50 response variables will be analyzed using a 
logistic regression model similar to the one specified for binary response variables in Section 
14.3.2.2 at timepoints not covered in the secondary efficacy analyses. 
Inserted section 14.3.3.3, Part B analysis for subjects who experience a flare 
The other efficacy variables for subjects who experience a flare in Part B as outlined in 
Section 4.1.3.3 will be summarized by visit and randomized treatment group using descriptive 
statistics for the timepoint itself and for the change from Baseline. A subset of variables will 
summarize the change from randomization Baseline (Week 48) and the change from the visit at 
which the flare occurred. This will be done for the FS using observed case data.
Change #54
14.4.1 Safety analyses
The frequency of all AEs by study period (Part A and Part B) will be presented for each 
treatment group separately by System Organ Class, high-level term, and preferred term. The data 
will be displayed as number of subjects experiencing the AEs, percentage of subjects, and 
number of AEs. Data will also be corrected for exposure by 100 patient years.
Has been changed to:
The frequency of all AEs by study period (Part A and Part B) will be presented separately by 
System Organ Class, high-level term, and preferred term and for Part B by each treatment group. 
The data will be displayed as number of subjects experiencing the AEs, percentage of subjects, 
and number of AEs. Data will also be corrected for exposure by 100 patient years.
Change #55
14.4.2 Pharmacokinetic analysis
Has been changed to: 
14.4.2 Pharmacokinetic and immunogenicity analysis
Change #56
14.8
Determination of sample size
It is anticipated that approximately 210 subjects will be randomized in a 1:1:1 ratio to the CZP 
200mg Q2W, CZP 200mg Q4W, and placebo treatment groups. The primary efficacy analysis is 
based on the proportion of subjects who do not experience a flare during Part B of the study. The 
proportion of subjects who do not experience a flare during Part B is assumed to be 80%, 75%, 
and 45% for the CZP 200mg Q2W, CZP 200mg Q4W, and placebo treatment groups, 
respectively. Given these assumptions, a sample size of 70 subjects per group provides 98% 
power to detect a significant difference between the CZP 200mg Q2W dose and placebo and 
94% power to detect a significant difference between the CZP 200mg Q4W dose and placebo 
using a 2-sided significance level of 0.05. Furthermore, a sample size of 70 subjects per arm 
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Page 147 of 173
provides 81% power to conclude that the CZP 200mg Q4W dose is noninferior to the CZP 
200mg Q2W dose, given a noninferiority margin of 15% and a 1-sided significance level of 
0.025.
Has been changed to:
It is anticipated that approximately 210 subjects will be randomized in a 1:1:1 ratio to the 
CZP 200mg Q2W, CZP 200mg Q4W, and placebo treatment groups. The primary efficacy 
analysis is based on the proportion of subjects who do not experience a flare during Part B of the 
study. The proportion of subjects who do not experience a flare during Part B is assumed to be 
80%, 75%, and 45% for the CZP 200mg Q2W, CZP 200mg Q4W, and placebo treatment groups, 
respectively. Given these assumptions, a sample size of 70 subjects per group provides 98% 
power to detect a significant difference between the CZP 200mg Q2W dose and placebo and 
94% power to detect a significant difference between the CZP 200mg Q4W dose and placebo 
using a 2-sided significance level of 0.05. 
Change #57
17 REFERENCES
The following reference was added:
Ware JE, Kosinski M, Bjorner J, Turner-Bowker D, Gandek B, Maruish M. Determining 
important differences in scores. User's Manual for the SF-36v2® Health Survey. Lincoln (RI): 
QualityMetric Incorporated; 2007:125-33.
Change #58
18.1
ASAS classification criteria for axSpA 
c Inflammatory back pain according to ASAS criteria for axSpA defined as the presence of 4 out of 5 of the
followingparameters:
1) age at onset <40 years
Has been changed to:
c Inflammatory back pain according to ASAS criteria for axSpA defined as the presence of 4 out of 5 of the
followingparameters:
1) age at onset <45 years
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18.4
Protocol Amendment 2
Rationale for the amendment
The main purpose of this amendment is to replace references to the current assay for measuring 
ADAbs in plasma samples (a validated screening ELISA method based on a double-antigen 
sandwich [bridge] format) with new methods in order to align with current regulatory guidelines. 
This change is being made across the CZP development program.
In the current version of the AS0005 protocol, an ADAb level >2.4 units/mL is defined as 
positive according to the bioanalytical method and testing strategy. The updated strategy for 
immunogenicity testing will take a tiered approach consisting of initial screening for ADAb
positive samples in subjects randomized to CZP or placebo, using a population-specific cutpoint 
resulting in a 5% false positive rate. Samples scored positively in the screening assay will be 
confirmed using a confirmatory assay with a population-specific confirmatory cutpoint resulting 
in a 1% false positive rate. Characterization of confirmed positive samples will consist of 
determination of the titer, and for a subset of samples, assessment of the neutralizing potential 
using a cell-based neutralizing antibody assay.
Moreover, one exclusion criterion (#28) was amended regarding one specific subcriterion: In the 
original version of the protocol, there was a differentiation of allowed Liver function test (LFT) 
values in patients with regard to concomitant MTX treatment (Liver function tests exclusionary 
if >2.0 x ULN for subjects treated with MTX and >ULN in subjects on concomitant MTX 
treatment). In line with other recent CZP protocols, this was now aligned that LFT >2.0 x ULN 
are exclusionary for all patients. During enrollment for the study, this was already handled in this
way in specifically discussed cases.
In line with the Statistical Analysis Plan (SAP) of the study, the Safety Set Part B (SSB) was 
added.
In addition, the wording of one inclusion criterion and of some other descriptional details was
modified for clarity and solving inconsistencies; current naming conventions were updated and 
typographical errors corrected.
Specific modifications and changesChange #1
Study contact information
Clinical Project Manager
Name:
Address:
Alfred-Nobel-Strasse 10
40789 Monheim, Germany
Phone:
Fax:
Clinical Trial Biostatistician
Name:
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 149 of 173
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Has been changed to:
Clinical Project Manager
Name:
Address:
Alfred-Nobel-Strasse 10
40789 Monheim, Germany
Phone:
Fax:
Clinical Trial Biostatistician
Name:
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Change #2
List of abbreviation
The following abbreviations were added:
NAb
Neutralizing antibody
PS
Patient Safety
SSB
Safety Set Part B
The following abbreviation was deleted:
DS
Drug Safety
Change #3
4.2.2
Biomarkers
Selected samples collected for measurement of CZP plasma concentration may be used 
additionally for analyses of the following biomarkers and cytokines: Matrix metalloproteinase-3 
(MMP-3); bone morphogenic protein (BMP) BMP-2, -4 and -7, wingless-related mouse 
mammary tumor virus integration site protein (WNT1), Inducible Signaling Pathway proteins 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 150 of 173
(WISP), Gremlin, Dickkopf-related protein 1 (DKK1), Sclerostin, Hedgehog proteins (Shh, Ihh, 
Dhh), Collagen turnover/cleavage products, collagen type X, vascular endothelial growth factor 
(VEGF), citrullinated vimentin fragments, cytokines: IL13, IL17 A and F, IL23, IL34, 
Transforming Growth Factor (TGF)β, Macrophage colony-stimulating factors (M-CSF), 
Granulocyte macrophage colony-stimulating factor (GM-CSF, CSF-1, soluble CSF-1 Receptor 
(sCSF1r) levels.
Has been changed to:
Selected samples collected for measurement of CZP plasma concentration may be used 
additionally for analyses of biomarkers and cytokines. These analyses may include, but are not 
limited to: Matrix metalloproteinase-3 (MMP-3); bone morphogenic protein (BMP) BMP-2, -4
and -7, wingless-related mouse mammary tumor virus integration site protein (WNT1), Inducible 
Signaling Pathway proteins (WISP), Gremlin, Dickkopf-related protein 1 (DKK1), Sclerostin, 
Hedgehog proteins (Shh, Ihh, Dhh), Collagen turnover/cleavage products, collagen type X, 
vascular endothelial growth factor (VEGF), citrullinated vimentin fragments, cytokines: IL13, 
IL17 A and F, IL23, IL34, Transforming Growth Factor (TGF)β, Macrophage colony-
stimulating factors (M-CSF), Granulocyte macrophage colony-stimulating factor (GM-CSF, 
CSF-1, soluble CSF-1 Receptor (sCSF1r) levels.
Change #4
4.2.3
Pharmacogenetic variables
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline, 
and, for genomic and proteomics analysis only, additionally at Weeks 12, 24, 48, 72, and 96/WD 
to enable exploratory evaluation of biomarkers relative to drug treatment and inflammatory and 
immune response processes. The samples will be stored at -80°C at the Central Laboratory 
facilities for up to 20 years or according to local laws.
Has been changed to:
Blood samples will be drawn for possible genetic, genomic, and proteomic analysis at Baseline, 
and, for genomic and proteomics analysis only, additionally at Weeks 12, 24, 48, 72, and 96/WD 
to enable exploratory evaluation of biomarkers relative to drug treatment and inflammatory and 
immune response processes. The samples will be stored at -80°C at the Biorepository for up to 
20 years or according to local laws.
Change #5
4.3 Immunogenicity variables
Anti-CZP antibody (ADAb) levels will be assessed at Baseline and subsequent timepoints as 
described in Table 5.1 and Table 5.2.
The number and percent of subjects with ADAb levels above 2.4units/mL will be reported as 
follows:

Number and % of subjects with ADAb >2.4units/mL at the time of each visit

Number and % of subjects with ADAb >2.4units/mL at any visit during treatment (not 
including posttreatment withdrawal or follow-up visits)
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 151 of 173

Number and % of subjects with ADAb >2.4units/mL at any visit including posttreatment 
withdrawal or follow-up visits
For the subgroup of subjects with at least 1 ADAb >2.4units/mL, the timepoint of occurrence of 
the first finding will also be displayed.
Has been changed to:
Anti-CZP antibody (ADAb) levels will be assessed at Baseline and subsequent timepoints as 
described in Table 5.1 and Table 5.2.
Determination of ADAb will be done using a validated screening, confirmation, and titration 
ADAb bridging assay, with potential further characterization by a neutralizing antibody (NAb) 
assay. The immunogenicity data will be processed according to dedicated Bioanalytical Analysis 
plans.
Change #6
5.2 Schedule of study assessments, Table 5.1
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 152 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Inclusion/exclusion
X
X
Informed consent c
X
Demographic data
X
Medical history 
(including axSpA 
and extra-articular 
manifestations 
history)
X
Vital signs d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology/urine/
biochemistry
Xe
X
X
X
X
X
X
X
X
X
X
X
CRP f
X 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testing g
X
X
X
X
PE h
X
X
X
X
X
X
X
X
X
X
X
Extra-articular 
assessments
X
X
X
X
X
X
X
X
X
X
X
X
Chest x-ray i
X
TB test j
X
X
X
TB questionnaire
X
X
X
X
X
X
X
X
X
X
Sacroiliac joint x-
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 153 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
ray k
MRI l
X
X
X
Stool sample m
X
X
X
Serum calprotectin
X
X
X
X
X
X
IBD-Questionnaire
X
X
X
BASMI and Spinal 
mobility n
X
X
X
X
X
X
X
X
X
X
X
X
X
BASDAI f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
AsQoL
X
X
X
X
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
X
X
X
X
X
MASES
X
X
X
X
X
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
X
X
X
X
X
X
X
X
Swollen and tender 
joint counts
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of 
Disease Activity f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of 
X
X
X
X
X
X
X
X
X
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 154 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Disease Activity
Work Productivity 
Survey
X
X
X
X
X
X
X
X
X
X
Resources 
utilization o
X
X
X
X
X
X
X
X
X
CZP plasma 
concentration/ 
ADAb 
X
X
X
X
X
X
X
X
X
X
Biomarker
X
X
X
X
X
X
X
X
X
X
Genetics
X
X
Genomics/ 
proteomics 
X
X
X
X
X
X
Prior and 
Concomitant 
medicationp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IXRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc self-
inj. at home
X
X
X
X
X
Randomization
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 155 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Nurse visit at subj. 
home (incl. study 
drug sc inj.) q
X
X
X
X
X
Check of sustained 
remission criteria r
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone Contact s
X
X
X
X
Abs=antibodies; ADAb= anti-CZP antibody concentration; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing Spondylitis Quality of Life; 
axSpA=axial spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; 
BASMI=Bath Ankylosing Spondylitis Metrology Index; CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; 
H=home, no site visit; HIV=human immunodeficiency virus; HLA-B27=human leukocyte antigen B27; HN=home nurse visit at subject’s home; 
IBD=Inflammatory bowel disease; incl.=including; inj=injection; IXRS=Interactive Voice or Web Response System; MASES=Maastricht Ankylosis Spondylitis 
Enthesitis Score; MRI=magnetic resonance imaging; PE=physical exam; sc=subcutaneously; SF-36=Short‑Form 36‑item Health Survey; SFU=Safety Follow-
Up; SI=sacroiliac; subj=subject; TB=tuberculosis; W=Week; WD=Withdrawal; WHO=World Health Organization
a Assessments conducted 3 to 5 days prior to Week 48 will serve as the qualification assessments for subjects determined to be eligible for randomization into 
Part B at Week 48.
b SFU: 10 weeks after last dose of study medication.
c Informed consent: Prior to any study activities, subjects will be asked to read and sign the informed consent form for the conduct of the study. A separate 
informed consent form will be obtained from subjects consenting also to the use of their blood samples for possible genetic, genomic, and proteomic analysis.
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening and Baseline, thereafter pulse rate, systolic 
and diastolic blood pressures and temperature are to be measured. If a subject experiences an AE, respiration rate will be measured in addition. 
e Testing to rule out hepatitis B surface antigen, antibodies to hepatitis C, antibodies to HIV and HLA-B27 at Screening only.
f To be assessed as indicated and from Week 52 onwards every 4 weeks only.
g Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and SFU and urine testing at Baseline and Week 96/WD 
Visit.
h Includes evaluation of signs and symptoms of active TB and risk factors for exposure to TB. Weight is to be measured at Screening, Baseline, Week 48, and at 
Week 96/WD. Height will be measured at the Baseline Visit only.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 156 of 173
i Screening chest x-ray must have occurred within 3 months prior to Screening Visit and should be repeated only if the TB test was confirmed positive or any 
further evidence is suggestive of potential TB infection (eg, exposure).
j QuantiFERON TB GOLD test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB GOLD test is not locally available. The TB test 
will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for subjects with previously negative TB test result.
k Sacroiliac joint x-rays will be performed at Screening and used as the Baseline assessment for all subjects. An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit may be used as the Baseline assessment provided that the film can be submitted and meets the requirements for central reading.
l Magnetic resonance imaging of the spine and sacroiliac joints to be performed at Screening, Week 48, and 96 or WD Visit if MRI was performed more than 
12 weeks prior to WD Visit.
m Kit for collection of stool sample to be provided at Screening Visit. Stool sample shall be obtained prior to Baseline and provided to the Investigator at the 
Baseline Visit.
n Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal flexion, cervical rotation, tragus to wall distance, 
and maximal intermalleolar distance.
o Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by the protocol, hospitalizations/emergency 
room visits.
p Prior medication will be at Screening only.
q Nurse visit at home only where approved and with agreement of subjects. Otherwise, the visit procedures will be done onsite by the site staff.
r Refer to Protocol Section 3 for definition. In case of loss of sustained remission in Part B, the subject must visit the study site for the next scheduled dose of 
study medication. The Investigator will initiate the escape treatment as appropriate. Refer to Table 5.2 for details.
s Subjects will be contacted by telephone about every 4 weeks in between the onsite visits
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This document cannot be used to support any marketing authoriza
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 157 of 173
Has been changed to:
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Inclusion/exclusion
X
X
Informed consent c
X
Demographic data
X
Medical history 
(including axSpA 
and extra-articular 
manifestations 
history)
X
Vital signs d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology/urine/
biochemistry
Xe
X
X
X
X
X
X
X
X
X
X
X
CRP f
X 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testing g
X
X
X
X
PE h
X
X
X
X
X
X
X
X
X
X
X
Extra-articular 
assessments
X
X
X
X
X
X
X
X
X
X
X
Chest x-ray i
X
TB test j
X
X
X
TB questionnaire
X
X
X
X
X
X
X
X
X
X
Sacroiliac joint x-
X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 158 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
ray k
MRI l
X
X
X
Stool sample m
X
X
X
Serum calprotectin
X
X
X
X
X
X
IBD-Questionnaire
X
X
X
BASMI and Spinal 
mobility n
X
X
X
X
X
X
X
X
X
X
X
X
X
BASDAI f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BASFI
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
AsQoL
X
X
X
X
X
X
X
X
X
X
X
EQ-5D
X
X
X
X
X
X
X
X
X
MASES
X
X
X
X
X
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
X
X
X
X
X
X
X
X
Swollen and tender 
joint counts
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of 
Disease Activity f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of 
X
X
X
X
X
X
X
X
X
X
REDACTED COPY 
PY
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OPY
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ny marketing authorization application and any extensions or variations thereof. 
24
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24
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PART B
or 
PART B
va
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3 (Doubl
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and
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 159 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Disease Activity
Work Productivity 
Survey
X
X
X
X
X
X
X
X
X
X
Resources 
utilization o
X
X
X
X
X
X
X
X
X
CZP plasma 
concentration/ 
ADAb 
X
X
X
X
X
X
X
X
X
X
Biomarker
X
X
X
X
X
X
X
X
X
X
Genetics
X
X
Genomics/ 
proteomics 
X
X
X
X
X
X
Prior and 
Concomitant 
medicationp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IXRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc self-
inj. at home
X
X
X
X
X
Randomization
X
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CO Y
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support any marketing authorization application and any extensions or variations thereof. 
24
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PART B
or 
PART B
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 160 of 173
Table 5.1:
Schedule of study assessments for all subjects completing Part A and Part B
PART A
PART B
Study Period
1 
(Screening)
2 (Open-Label)
3 (Double-Blind)
4
             Week (W)
Protocol Activity
-5 to -1 
weeks
0
2
4
6 
to 
10 
H
12
14 
to 
22 
H
24
26 
to 
30 
H
32
34 
H
36
38 
to 
46 
H
3-5 
days 
prior 
to 
W48 
visita
48
50 
HN
52
54 
to 
58 
HN
60
62 
to 
70 
HN
72
74 
to 
82 
HN
84
86 
to 
94 
HN
96/ 
WD
SFU
b
Nurse visit at subj. 
home (incl. study 
drug sc inj.) q
X
X
X
X
X
Check of sustained 
remission criteria r
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telephone Contact s
X
X
X
X
Abs=antibodies; ADAb=anti-CZP antibody; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing Spondylitis Quality of Life; axSpA=axial 
spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath 
Ankylosing Spondylitis Metrology Index; CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site 
visit; HIV=human immunodeficiency virus; HLA-B27=human leukocyte antigen B27; HN=home nurse visit at subject’s home; IBD=Inflammatory bowel 
disease; incl.=including; inj=injection; IXRS=Interactive Voice or Web Response System; MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; 
MRI=magnetic resonance imaging; PE=physical exam; sc=subcutaneously; SF-36=Short‑Form 36‑item Health Survey; SFU=Safety Follow-Up; SI=sacroiliac; 
subj=subject; TB=tuberculosis; W=Week; WD=Withdrawal; WHO=World Health Organization
a Assessments conducted 3 to 5 days prior to Week 48 will serve as the qualification assessments for subjects determined to be eligible for randomization into 
Part B at Week 48.
b SFU: 10 weeks after last dose of study medication.
c Informed consent: Prior to any study activities, subjects will be asked to read and sign the informed consent form for the conduct of the study. A separate 
informed consent form will be obtained from subjects consenting also to the use of their blood samples for possible genetic, genomic, and proteomic analysis.
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening and Baseline, thereafter pulse rate, systolic 
and diastolic blood pressures and temperature are to be measured. If a subject experiences an AE, respiration rate will be measured in addition. 
e Testing to rule out hepatitis B surface antigen, antibodies to hepatitis C, antibodies to HIV and HLA-B27 at Screening only.
f To be assessed as indicated and from Week 52 onwards every 4 weeks only.
g Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and SFU and urine testing at Baseline and Week 96/WD 
Visit.
h Includes evaluation of signs and symptoms of active TB and risk factors for exposure to TB. Weight is to be measured at Screening, Baseline, Week 48, and at 
Week 96/WD. Height will be measured at the Baseline Visit only.
TED COPY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 161 of 173
i Screening chest x-ray must have occurred within 3 months prior to Screening or during Screening, and should be repeated only if the TB test was confirmed 
positive or any further evidence is suggestive of potential TB infection (eg, exposure).
j QuantiFERON TB GOLD test or another WHO-validated IGRA test such as Elispot test, if QuantiFERON TB GOLD test is not locally available. The TB test 
will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for subjects with previously negative TB test result.
k Sacroiliac joint x-rays will be performed at Screening and used as the Baseline assessment for all subjects. An SIJ x-ray performed ≤12 months prior to the 
Baseline Visit may be used as the Baseline assessment provided that the film can be submitted and meets the requirements for central reading.
l Magnetic resonance imaging of the spine and sacroiliac joints to be performed at Screening, and within a ± 2 weeks time window at Weeks 48 and 96 or WD 
Visit if MRI was performed more than 12 weeks prior to WD Visit.
m Kit for collection of stool sample to be provided at Screening Visit. Stool sample shall be obtained prior to Baseline and provided to the Investigator at the 
Baseline Visit.
n Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal flexion, cervical rotation, tragus to wall distance, 
and maximal intermalleolar distance.
o Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by the protocol, hospitalizations/emergency 
room visits.
p Prior medication will be at Screening only.
q Nurse visit at home only where approved and with agreement of subjects. Otherwise, the visit procedures will be done onsite by the site staff.
r Refer to Protocol Section 3 for definition. In case of loss of sustained remission in Part B, the subject must visit the study site for the next scheduled dose of
study medication. The Investigator will initiate the escape treatment as appropriate. Refer to Table 5.2 for details.
s Subjects will be contacted by telephone about every 4 weeks in between the onsite visits.
COPY
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This document cannot be used to support any marketing authorizatio
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atio
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 162 of 173
Change #7
5.2 Schedule of study assessments, Table 5.2
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Vital signs d
X
X
X
X
Hematology/urine/ biochemistry
X
X
CRP e
X
X
X
X f
X
X f
Stool sample g
X
X
Serum calprotectin g
X
X
IBD-Questionnaire g
X
X
PE 
X
X
X
X
Extra-articular assessments
X
X
X
MRI h
X
X
TB questionnaire
X
X
BASMI & Spinal mobility i
X
X
X
X
BASDAI
X
X
X
X f
X
X f
BASFI
X
X
X
X
SF-36
X
X
X
AsQoL
X
X
X
X
EQ-5D
X
X
X
MASES
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
Patient’s Global Assessment of Disease Activity
X
X
X
X f
X
X f
Physician’s Global Assessment of Disease Activity
X
X
X
X
Work Productivity Survey
X
X
X
Resources utilization j
X
X
X
CZP plasma concentration/ADAb
X
X
X
X
Biomarker
X
X
X
X
TED COPY 
X
PY
X
Y
X
O
X
OP
CO
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 163 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Concomitant medication
X
X
X
X
AEs
X
X
X
X
IXRS
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
Study drug sc self-inj. at home
X
X
Telephone Contact k
X
X
Abs=antibodies; ADAb=anti-CZP antibody concentration; AEs=adverse events; AS=ankylosing spondylitis; 
AsQoL=Ankylosing Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; 
BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; 
CRP=C-reactive protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site 
visit; HN=home nurse visit at subjects home; IBD=Inflammatory bowel disease; IXRS=Interactive Voice or Web 
Response System; MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; MRI=magnetic resonance imaging; 
PE=physical exam; sc=subcutaneously; SF-36=Short-Form 36-item Health Survey; TB=tuberculosis; W=Week
a HN Q4W only for obtaining blood sample (CRP) and electronic patient reported outcome (ePRO) data as 
indicated 
b Schedule onsite visit every 12 weeks until Week 96 of regular visit schedule is reached. For example, at Weeks 74 
and 86, if start of escape treatment is at Week 62 (=Escape Week 0). At Week 96 and SFU, perform assessments 
as described in Table 5.1. For subjects experiencing a flare at/after Week 82, escape treatment should be provided 
for 12 weeks and the subject invited for the final assessment visit (as laid down for Week 96) 2 weeks later 
c Until 2 weeks before Week 96 of regular visit schedule is reached
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening 
and Baseline, thereafter pulse rate, systolic and diastolic blood pressures and temperature are to be measured. If a 
subject experiences an AE, respiration rate will be measured in addition
e To be assessed as indicated and from Week 52 onwards every 4 weeks only
f To be assessed every 4 weeks only
g To be assessed at escape Weeks 0 and 12 only
h To be performed at escape Weeks 0 and 12 only and at final assessment visit at Week 96, if the last MRI was done 
at least 12 weeks prior to Week 96
i Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal 
flexion, cervical rotation, tragus to wall distance, and maximal intermalleolar distance.
j Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by 
the protocol, hospitalizations/emergency room visits
k Subjects will be contacted by telephone about every 4 weeks in between the onsite visits
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 164 of 173
Has been changed to:
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
Vital signs d
X
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X
X
Hematology/urine/ biochemistry
X
X
CRP e
X
X
X
X f
X
X f
Stool sample g
X
X
Serum calprotectin g
X
X
IBD-Questionnaire g
X
X
PE 
X
X
X
X
Extra-articular assessments
X
X
X
MRI h
X
X
TB questionnaire
X
X
BASMI & Spinal mobility i
X
X
X
X
BASDAI
X
X
X
X f
X
X f
BASFI
X
X
X
X
SF-36
X
X
X
AsQoL
X
X
X
X
EQ-5D
X
X
X
MASES
X
X
X
X
Total and nocturnal
spinal pain
X
X
X
X
Patient’s Global Assessment of Disease Activity
X
X
X
X f
X
X f
Physician’s Global Assessment of Disease Activity
X
X
X
X
Work Productivity Survey
X
X
X
Resources utilization j
X
X
X
CZP plasma concentration/ADA
X
X
X
X
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X
X
X
X
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X
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 165 of 173
Table 5.2:
Schedule of study assessments for all subjects experiencing a flare 
in Part B
Part B for subjects experiencing a flare
Study-Period
3B
Visit / week (W) on escape treatment
0
2
4
6 
to 
10 
H/H
N a
12 (and 
every 12 
weeks 
thereafter) b
every 2 weeks in 
between c
H/HN a
Protocol Activity
AEs
X
X
X
X
IXRS
X
X
X
X
X
X
Study drug sc onsite
X
X
X
X
Study drug sc self-inj. at home
X
X
Telephone Contact k
X
X
Abs=antibodies; ADAb=anti-CZP antibody; AEs=adverse events; AS=ankylosing spondylitis; AsQoL=Ankylosing 
Spondylitis Quality of Life; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath 
Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; CRP=C-reactive 
protein; CZP=certolizumab pegol; EQ-5D=EuroQoL Health Status Questionnaire; H=home, no site visit; HN=home 
nurse visit at subjects home; IBD=Inflammatory bowel disease; IXRS=Interactive Voice or Web Response System; 
MASES=Maastricht Ankylosis Spondylitis Enthesitis Score; MRI=magnetic resonance imaging; PE=physical exam; 
sc=subcutaneously; SF-36=Short-Form 36-item Health Survey; TB=tuberculosis; W=Week
a HN Q4W only for obtaining blood sample (CRP) and electronic patient reported outcome (ePRO) data as 
indicated 
b Schedule onsite visit every 12 weeks until Week 96 of regular visit schedule is reached. For example, at Weeks 74 
and 86, if start of escape treatment is at Week 62 (=Escape Week 0). At Week 96 and SFU, perform assessments 
as described in Table 5.1. For subjects experiencing a flare at/after Week 82, escape treatment should be provided 
for 12 weeks and the subject invited for the final assessment visit (as laid down for Week 96) 2 weeks later 
c Until 2 weeks before Week 96 of regular visit schedule is reached
d Pulse rate, systolic and diastolic blood pressures, temperature, and respiration rate are to be measured at Screening 
and Baseline, thereafter pulse rate, systolic and diastolic blood pressures and temperature are to be measured. If a 
subject experiences an AE, respiration rate will be measured in addition
e To be assessed as indicated and from Week 52 onwards every 4 weeks only
f To be assessed every 4 weeks only (Week 8, 12, 16, 20, 24, … up to Week 96)
g To be assessed at escape Weeks 0 and 12 only
h To be performed at escape Weeks 0 and 12 only and at final assessment visit at Week 96, if the last MRI was done 
at least 12 weeks prior to Week 96. Magnetic resonance imaging is to be performed within a ±2-weeks time 
window.
i Occiput to wall distance; chest expansion; and BASMI, which includes modified Schober test, lateral spinal 
flexion, cervical rotation, tragus to wall distance, and maximal intermalleolar distance.
j Resource utilization includes: concomitant medical procedures, health care provider consultations not foreseen by 
the protocol, hospitalizations/emergency room visits
k Subjects will be contacted by telephone about every 4 weeks in between the onsite visits
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 166 of 173
Change #8
Section 6.1
Inclusion criteria, inclusion criterion 5
5. Subjects must have a documented diagnosis of adult-onset axSpA with at least 3 months' 
symptom duration as defined by the specified ASAS criteria (according to Appendix 18.1) and 
symptom duration of less than 5 years prior to the participation of this study.
Has been changed to:
5. Subjects must have a documented diagnosis of adult-onset axSpA with at least 3 months' 
symptom duration and meet the ASAS classification criteria for axSpA (according to Appendix
18.1) and symptom duration of less than 5 years prior to the participation of this study.
Change #9
6.2 Exclusion criteria, criterion 28
28. Subjects with significant laboratory abnormalities included but not limited to: 

Liver function tests >2.0 x ULN, if the subject is not treated with MTX and >ULN if 
subject is on concomitant MTX treatment

Estimated Glomerular Filtration Rate (GFR) as measured by Chronic Kidney Disease 
Epidemiology Collaboration (Levey et al, 2009) <60 mL/min/1.73m2

White blood cell (WBC) <3.0x109/L.
Has been changed to:
28. Subjects with significant laboratory abnormalities included but not limited to: 

Liver function tests >2.0 x ULN

Estimated Glomerular Filtration Rate (GFR) as measured by Chronic Kidney Disease 
Epidemiology Collaboration (Levey et al, 2009) <60 mL/min/1.73m2

Wite blood cell (WBC) <3.0x109/L
Change #10
7.9 Blinding (first paragraph)
Due to differences in presentation and viscosity between active and placebo, special precautions 
will be taken in order to ensure blinding of the study during Part B. The subject will receive the 
IMP throughout the study duration for each single administration in a sealed box with a PFS 
containing either CZP 200mg or placebo. Packaging and labeling will be done in a way to ensure 
that the provided box including the PFS will not provide any information about the assigned 
treatment of the study (CZP 200mg or placebo). Administration of the IMP will be done 
according to the schedule of study assessments (Table 5.1) either onsite by appropriately trained 
unblinded study personnel or at home by the unblinded home nurse. C-reactive protein, PK, and 
antibody data will be provided only after the study is unblinded.
[…]
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 167 of 173
Has been changed to:
Due to differences in presentation and viscosity between active and placebo, special precautions 
will be taken in order to ensure blinding of the study during Part B. The subject will receive the 
IMP throughout the study duration for each single administration in a sealed box with a PFS 
containing either CZP 200mg or placebo. Packaging and labeling will be done in a way to ensure 
that the provided box including the PFS will not provide any information about the assigned 
treatment of the study (CZP 200mg or placebo). Administration of the IMP will be done 
according to the schedule of study assessments (Table 5.1) either onsite by appropriately trained 
unblinded study personnel or at home by the unblinded home nurse.
[…]
Change #11
8
Study procedures by visit
Section 5.2 (Schedule of assessments) provides a general overview of study assessments. A 
detailed listing of procedures to be undertaken at each visit is described below. 
During the study, the Investigator will assess each subject over the entire study period of up to 
109 weeks including a SFU Period of 10 weeks after the last dose. Visit windows of ±3 days on 
either side of the scheduled dosing are permitted; however, the Investigator should try to keep 
the subjects on the original dosing schedule. The window of ±3 days is relative to Baseline and 
applicable for all subsequent visits. Changes to the dosing schedule outside of the 3-day window 
must be discussed with the Medical Monitor and may result in subject withdrawal.
Has been changed to:
Section 5.2 (Schedule of assessments) provides a general overview of study assessments. A 
detailed listing of procedures to be undertaken at each visit is described below. 
During the study, the Investigator will assess each subject over the entire study period of up to 
109 weeks including a SFU Period of 10 weeks after the last dose. Visit windows of ±3 days on 
either side of the scheduled dosing are permitted; however, the Investigator should try to keep 
the subjects on the original dosing schedule. The window of ±3 days is relative to Baseline and 
applicable for all subsequent visits. Changes to the dosing schedule outside of the 3-day window 
must be discussed with the Medical Monitor and may result in subject withdrawal. For the 
conduct of MRI, the acceptable time window is ±2 weeks.
Change #12
8.1 Screening Visit (up to 5 weeks)
[…]

Physical examination (including weight, evaluation of signs and symptoms of active TB and 
risk factors for exposure to TB) and extra-articular assessment
[…]
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 168 of 173
Has been changed to:
[…]

Physical examination (including weight, evaluation of signs and symptoms of active TB and 
risk factors for exposure to TB)
[…]
Change #13
9.1.4
MRI assessments
Magnetic resonance imaging of the spine and sacroiliac joints will be performed at Screening, 
Week 48, Week 96, or WD Visit if MRI was performed more than 12 weeks prior to WD. 
Magnetic resonance imaging will be assessed centrally and scoring will be done by 2 
independent readers, who are blinded to both the order of the scans and to the treatment group, 
using a previously reported scoring system.
[…]
Has been changed to:
Magnetic resonance imaging of the spine and sacroiliac joints will be performed at Screening, 
Week 48, Week 96, or WD Visit if MRI was performed more than 12 weeks prior to WD. 
Magnetic resonance imaging will be assessed centrally and scoring will be done by
2 independent readers, who are blinded to both the order of the scans and to the treatment group, 
using a previously reported scoring system. In addition, a single reader assessment will be 
performed for change from Baseline (Week 48) evaluation in sacroiliac SPARCC and 
ASspIMRI-a in the Berlin-modification scores for all subjects that entered Part A.
Change #14
10 Assessment of pharmacokinetics and pharmacogenomic variables
Plasma samples for the measurement of CZP concentrations will be taken at Baseline and Weeks 
4, 12, 24, 48, 60, 72, 84, 96/WD, and at the SFU visit 10 weeks after the last dose of study 
medication. For escapers plasma samples will be taken after the flare at Escape Weeks 0, 2, 4, 
12, and further every 12 weeks until Week 96/WD (refer to Table 5.2 for details). These plasma 
samples may be used additionally for analyses of CZP and its constituent moieties using 
alternative methods and the results of those analyses may be reported separately.
Plasma samples for possible analyses of exploratory biomarkers will be taken at Baseline and 
Weeks 4, 12, 24, 48, 60, 72, 84, 96/WD, and at the SFU visit 10 weeks after the last dose of 
study medication. For escapers plasma samples will be taken after the flare at Escape Weeks 0, 
2, 4, 12, and further every 12 weeks until Week 96/WD (refer to Table 5.2 for details). Selected 
biomarkers that may be analyzed are: MMP-3; BMP-2, -4, and -7, WNT1, WISP, Gremlin, 
DKK1, Sclerostin, Hedgehog proteins (Shh, Ihh, Dhh), Collagen turnover/cleavage products, 
collagen type X, VEGF, citrullinated vimentin fragments, cytokines: IL13, IL17 A and F, IL23, 
IL34, TGF-β, M-CSF, GM-CSF, CSF-1, sCSF1r levels.
[…]
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 169 of 173
Has been changed to:
Plasma samples for the measurement of CZP concentrations will be taken at Baseline and 
Weeks 4, 12, 24, 3 to 5 days prior to Week 48, and Weeks 60, 72, 84, 96/WD, and at the SFU 
visit 10 weeks after the last dose of study medication. For escapers plasma samples will be taken 
after the flare at Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer 
to Table 5.2 for details). These plasma samples may be used additionally for analyses of CZP 
and its constituent moieties using alternative methods and the results of those analyses may be 
reported separately.
Plasma samples for possible analyses of exploratory biomarkers will be taken at Baseline and 
Weeks 4, 12, 24, 3 to 5 days prior to Week 48, and Weeks 60, 72, 84, 96/WD, and at the SFU 
visit 10 weeks after the last dose of study medication. For escapers plasma samples will be taken 
after the flare at Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer 
to Table 5.2 for details). Selected biomarkers that may be analyzed are: MMP-3; BMP-2, -4, and 
-7, WNT1, WISP, Gremlin, DKK1, Sclerostin, Hedgehog proteins (Shh, Ihh, Dhh), Collagen 
turnover/cleavage products, collagen type X, VEGF, citrullinated vimentin fragments, cytokines: 
IL13, IL17 A and F, IL23, IL34, TGF-β, M-CSF, GM-CSF, CSF-1, sCSF1r levels.
[…]
Change #15
11 Assessment of immunogenicity variables
Plasma samples for the measurement of ADAb levels will be taken at Baseline (Week 0) and 
Weeks 4, 12, 24, 48, 60, 72, 84, 96, and the SFU visit (10 weeks after the last dose of study 
medication). For escapers plasma samples will be taken after the flare at Escape Weeks 0, 2, 4, 
12, and further every 12 weeks until Week 96/WD (refer to Tabke 5.2 for details). The number 
and percent of subjects with ADAb levels above 2.4units/mL will be reported as follows:

At the time of each visit

At any visit during treatment (not including posttreatment withdrawal or follow-up visits)

At any visit including posttreatment withdrawal or follow-up visits.
The sampling, handling, and shipment of samples will be performed as detailed in the Laboratory 
Manual. 
Has been changed to:
Plasma samples for the measurement of ADAb and potentially NAb levels will be taken at 
Baseline (Week 0) and Weeks 4, 12, 24, 48, 60, 72, 84, 96, and the SFU visit (10 weeks after the 
last dose of study medication). For escapers, plasma samples will be taken after the flare at 
Escape Weeks 0, 2, 4, 12, and further every 12 weeks until Week 96/WD (refer to Table 5.2 for 
details).
The sampling, handling, and shipment of samples will be performed as detailed in the Laboratory 
Manual.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 170 of 173
Change #16
12.6
Laboratory measurements, first sentence
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline
(Week 0), Weeks 12, 24, 32, 36, 3 to 5 days prior to 48, and 60, 72, 84, 96/WD, and at the SFU 
Visit (10 weeks after the last dose).
Has been changed to:
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline
(Week 0), Weeks 12, 24, 32, 36, 3 to 5 days prior to Week 48, and Weeks 60, 72, 84, 96/WD, 
and at the SFU Visit (10 weeks after the last dose).
Change #17
14.1
Definition of analysis sets
The following analysis set has been added:
The Safety Set Part B (SSB) will consist of all subjects in the RS who have received at least 
1 dose of study medication in the Double-Blind Period of the study (Part B).
Change #18
14.1
Definition of analysis sets, last sentence
[…]
The Pharmacokinetic Set B (PKSB) will consist of all subjects from the SS who provide at least 
1 PK sample during Part B.
Has been changed to:
[…]
The Pharmacokinetic Set B (PKSB) will consist of all subjects from the SSB who provide at 
least 1 PK sample during Part B.
Change #19
14.2
General statistical considerations
The second test is performed only if the first test is significant at the 0.05 level. 
Has been changed to:
The second test will be performed irrespective of whether the first test is significant at the 0.05 
level or not. However, the second test will be interpreted as statistically significant only if the 
first test is significant at the 0.05 level as well.
Change #20
14.3.1 Analysis of the primary efficacy variable, 3rd paragraph
Subgroup analyses based on age, gender, race, region, CRP level, ADAb status (> or 
≤2.4 units/mL), and mNY criteria will be performed. These analyses will be done for the primary 
efficacy variable and will be based on descriptive statistics only. 
REDACTED COPY 
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 171 of 173
Has been changed to:
Subgroup analyses based on age, gender, race, region, CRP level, ADAb status, and mNY 
criteria will be performed. These analyses will be done for the primary efficacy variable and will 
be based on descriptive statistics only.
Change #21
14.4.1 Safety analyses, last sentence
Laboratory evaluations and vital signs will be analyzed over time in the SS for observed cases 
and at the end of treatment.
Has been changed to:
Laboratory evaluations and vital signs will be analyzed over time in the SS and SSB for observed 
cases and at the end of treatment.
Change #22
14.4.2 Pharmacokinetic and immunogenicity analysis
Certolizumab pegol plasma concentrations will be tabulated and summarized by treatment group 
(overall and by ADAb levels within each treatment group) for each visit at which samples were 
taken using the geometric mean, 95% CI, geometric coefficient of variation, arithmetic mean, 
arithmetic SD, median, minimum, and maximum. For each treatment group, plasma 
concentration time curves will be plotted overall and by antibody level (above or below 
2.4units/mL).
Subgroup analyses based on age, gender, race, region, CRP level, antibody level, and mNY 
criteria will be performed. For the subgroup of subjects with at least 1 ADAb level above 
2.4units/mL, the timepoint of occurrence of the first finding will also be displayed.
Frequency tables of ADAb level by visit will be presented. In addition, safety and efficacy 
profiles by ADAb level will be investigated.
Has been changed to:
Certolizumab pegol plasma concentrations will be tabulated and summarized by treatment group 
for each visit at which samples were taken using the geometric mean, 95% CI, geometric 
coefficient of variation, arithmetic mean, arithmetic SD, median, minimum, and maximum. 
Immunogenicity will be assessed through listing of individual results by subject and summary
tables. Immunogenicity data will be correlated with PK and efficacy readout. In addition, 
immunogenicity will be correlated with possible safety findings.
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 172 of 173
19
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
REDACTED COPY 
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OP
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Date/Sig
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Date/Sig
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UCB
24 Jan 2018
Clinical Study Protocol
Certolizumab Pegol
AS0005
Confidential
Page 173 of 173
20
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 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 

 
 
 
 
 
 
 
 
ELECTRONIC SIGNATURES 
 
Signed by 
Meaning of Signature 
Server Approval Date 
(dd-mon-yyyy 
(HH:mm)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
as0005-protocol-amend-2
Clinical Approval
24-Jan-2018 12:07 GMT+01
Clinical Approval
24-Jan-2018 13:33 GMT+01
Clinical Approval
24-Jan-2018 21:07 GMT+01
ED COPY 
ED
REDACT
DA
al
O
al
Appro
CTED
Appro
authorization application and any extensions or variations thereof. 
n an
any 
Server
any
Server
nd a
an
upport any marketing au
y
n a
au
ke
an
This document cannot be used to sup
up
se
val
oriz
val