Conditions: Axial Spondyloarthritis (axSpA) Anterior Uveitis (AU)
Keywords: Axial Spondyloarthritis axSpA Anterior Uveitis Certolizumab Pegol Cimzia
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 89
Healthy volunteers: no

Brief summary:
The purpose of the study is to demonstrate the effect of Certolizumab Pegol (CZP) treatment on the reduction of Anterior Uveitis (AU) flares in subjects with active axial Spondyloarthritis (axSpA) and a documented history of AU.

Detailed description:

Arms:
arm 1: Subjects will receive a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc every two Weeks

Interventions: intervention 1: Certolizumab Pegol
Intervention descriptions: intervention 1: * pharmaceutical form: solution for infusion in prefilled syringe
* concentration: 200 mg/mL
* route of administration: subcutaneous

Protocol document:
Prot_000.pdf: 
UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 1 of 113
PROTOCOL AS0007 AMENDMENT 3 
MULTICENTER, OPEN-LABEL STUDY TO ASSESS THE 
EFFECTS OF CERTOLIZUMAB PEGOL ON THE REDUCTION 
OF ANTERIOR UVEITIS FLARES IN AXIAL 
SPONDYLOARTHRITIS SUBJECTS WITH A HISTORY OF 
ANTERIOR UVEITIS (C-VIEW) 
PHASE 4 
EudraCT Number: 2016-000343-14 
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Protocol/Amendment number
Date
Type of 
amendment
Final protocol
14 Apr 2016
Not applicable
Protocol amendment 1
03 Jun 2016
Non-substantial
Protocol amendment 1.1 (Spain)
28 Oct 2016
Non-substantial
Protocol amendment 2
17 Jan 2017
Substantial
Protocol amendment 2.1 (Spain)
06 Apr 2017
Substantial
Protocol amendment 3
22 Jan 2020
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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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 2 of 113
STUDY CONTACT INFORMATION 
Sponsor 
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Principal/Coordinating Investigator 
Name:
Dr. 
Affiliation:
VUMC afd. Reumatologie
Address:
VUMC afd. Reumatologie
Kamer 3A- 64
Postbus 7057 1007MB Amsterdam
NETHERLANDS
Phone:
Fax:
Sponsor Study Physician 
Name:
, MD
Address:
UCB Biosciences GmbH
Alfred-Nobel-Str 10
40789 Monheim/Rhein
GERMANY
Phone:
Fax:
RE
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 3 of 113
Clinical Project Manager 
Name:
Address:
UCB Biopharma SPRL
Allée de la Recherche 60
1070 Brussels
BELGIUM
Phone:
Fax:
Clinical Trial Biostatistician 
Name:
Dr. 
Address:
UCB Biosciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
Germany
Phone:
Fax:
Clinical Monitoring Contract Research Organization 
Name:
PRA Health Sciences 
Address:
500 South Oak Way
Green Park
Reading
Berkshire, RG2 6AD 
UNITED KINGDOM
Phone:
+44 (118) 918 1000
Fax:
+44 (118) 918 1001
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 4 of 113
SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h)
Fax:
+32 2 386 24 21
Email:
DS_ICT@ucb.com
REDACTED COPY 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 5 of 113
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS..................................................................................................10 
1 
SUMMARY.....................................................................................................................13 
2 
INTRODUCTION ...........................................................................................................14 
2.1 
Natural history of axial spondyloarthritis ....................................................................14 
2.2 
Uveitis in axial spondyloarthritis.................................................................................15 
2.3 
Diagnosing axial spondyloarthritis in clinical practice................................................16 
2.4 
Current management of axial spondyloarthritis and uveitis ........................................17 
2.5 
Rationale ......................................................................................................................18 
3 
STUDY OBJECTIVE(S).................................................................................................19 
3.1 
Primary objective.........................................................................................................19 
3.2 
Secondary objectives ...................................................................................................19 
3.3 
Other objectives ...........................................................................................................19 
3.4 
Safety objective............................................................................................................19 
4 
STUDY VARIABLES.....................................................................................................19 
4.1 
Efficacy variables.........................................................................................................19 
4.1.1 
Primary efficacy variable.....................................................................................19 
4.1.2 
Secondary efficacy variables ...............................................................................19 
4.1.3 
Other efficacy variables.......................................................................................20 
4.2 
Safety variables............................................................................................................21 
4.2.1 
Secondary safety variable....................................................................................21 
4.2.2 
Other safety variables ..........................................................................................21 
5 
STUDY DESIGN.............................................................................................................21 
5.1 
Study description .........................................................................................................21 
5.1.1 
Study duration per subject ...................................................................................22 
5.1.2 
Planned number of subjects and sites ..................................................................22 
5.1.3 
Anticipated regions and countries .......................................................................22 
5.2 
Schedule of study assessments.....................................................................................22 
5.3 
Schematic diagram.......................................................................................................27 
5.4 
Rationale for study design and selection of dose.........................................................28 
6 
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................28 
6.1 
Inclusion criteria ..........................................................................................................28 
6.2 
Exclusion criteria .........................................................................................................29 
6.3 
Withdrawal criteria ......................................................................................................34 
7 
STUDY TREATMENT(S) ..............................................................................................35 
7.1 
Description of investigational medicinal product(s)....................................................35 
7.2 
Treatment(s) to be administered ..................................................................................36 
7.3 
Packaging.....................................................................................................................36 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 6 of 113
7.4 
Labeling .......................................................................................................................36 
7.5 
Handling and storage requirements .............................................................................36 
7.5.1 
Storage at the site.................................................................................................36 
7.5.2 
Storage at the subject’s home ..............................................................................37 
7.6 
Drug accountability......................................................................................................37 
7.7 
Procedures for monitoring subject compliance............................................................37 
7.8 
Concomitant medication(s)/treatment(s) .....................................................................38 
7.8.1 
Permitted concomitant treatments (medications and therapies) ..........................38 
7.8.2 
Prohibited concomitant treatments (medications and therapies).........................39 
7.8.3 
Rescue medication...............................................................................................39 
7.9 
Blinding........................................................................................................................39 
7.10 
Enrollment into treatment and numbering of subjects.................................................39 
8 
STUDY PROCEDURES BY VISIT ...............................................................................40 
8.1 
Visit 1 (Week -5 to -1) Screening................................................................................40 
8.2 
Visit 2 (Week 0) Baseline Visit ...................................................................................42 
8.3 
Visit 3 and 4 (Week 2 and 4) .......................................................................................43 
8.4 
Visits 5 and 6, and Visits 8 to 12 (Weeks 12, 24, 36, 48, 60, 72, and 84)...................44 
8.5 
Visit 7 (Week 32).........................................................................................................45 
8.6 
Visit 13 (Week 96/Withdrawal Visit)..........................................................................45 
8.7 
Visit 14 (Follow-Up Visit)...........................................................................................46 
8.8 
Unscheduled Visit........................................................................................................46 
9 
ASSESSMENT OF EFFICACY......................................................................................47 
9.1 
Assessment of primary and secondary efficacy variables ...........................................47 
9.1.1 
Assessment of AU flares .....................................................................................47 
9.1.2 
Ankylosing spondylitis disease activity score (ASDAS) ....................................47 
9.1.3 
Bath ankylosing spondylitis disease activity index (BASDAI)...........................48 
9.1.4 
ASAS20, ASAS40, ASAS5/6, and ASAS PR.....................................................49 
9.1.5 
Physician’s global assessment of disease activity (PhGADA)............................49 
9.1.6 
Swollen and tender joint counts (44 joints evaluation)........................................49 
9.1.7 
Patient’s global assessment of disease activity (PtGADA) (NRS)......................50 
9.1.8 
Total and nocturnal spinal pain NRS...................................................................50 
9.1.9 
Bath ankylosing spondylitis functional index (BASFI).......................................50 
9.1.10 
Extra-articular assessments..................................................................................51 
9.2 
Assessment of other efficacy variables........................................................................51 
9.2.1 
Ankylosing spondylitis quality of life (ASQoL) .................................................51 
9.2.2 
ASAS HI Questionnaire ......................................................................................51 
9.2.3 
Short-Form 36-Item Health Survey (SF-36)........................................................52 
10 ASSESSMENT OF SAFETY..........................................................................................52 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 7 of 113
10.1 
Adverse events.............................................................................................................52 
10.1.1 
Definition of adverse event..................................................................................52 
10.1.2 
Procedures for reporting and recording adverse events.......................................53 
10.1.3 
Description of adverse events..............................................................................53 
10.1.4 
Follow up of adverse events ................................................................................53 
10.1.5 
Rule for repetition of an adverse event................................................................53 
10.1.6 
Pregnancy ............................................................................................................54 
10.1.7 
Overdose of investigational medicinal product ...................................................54 
10.1.8 
Safety signal detection.........................................................................................55 
10.2 
Serious adverse events .................................................................................................55 
10.2.1 
Definition of serious adverse event .....................................................................55 
10.2.2 
Procedures for reporting serious adverse events .................................................56 
10.2.3 
Follow up of serious adverse events....................................................................56 
10.3 
Adverse events of interest............................................................................................57 
10.4 
Immediate reporting of adverse events........................................................................57 
10.5 
Anticipated serious adverse events ..............................................................................57 
10.6 
Laboratory measurements............................................................................................58 
10.6.1 
Pregnancy testing.................................................................................................60 
10.6.2 
Physical assessments ...........................................................................................60 
10.6.3 
MRI assessments .................................................................................................60 
10.6.4 
Tuberculosis assessments ....................................................................................60 
10.6.4.1 
Tuberculosis test........................................................................................60 
10.6.4.2 
Chest x-ray ................................................................................................62 
10.6.4.3 
Tuberculosis questionnaire........................................................................62 
11 STUDY MANAGEMENT AND ADMINISTRATION.................................................63 
11.1 
Adherence to protocol..................................................................................................63 
11.2 
Monitoring ...................................................................................................................63 
11.2.1 
Definition of source data .....................................................................................63 
11.2.2 
Source data verification .......................................................................................64 
11.3 
Data handling...............................................................................................................64 
11.3.1 
Case Report Form completion.............................................................................64 
11.3.2 
Electronic reporting outcome ..............................................................................65 
11.3.3 
Database entry and reconciliation........................................................................65 
11.3.4 
Subject Screening and Enrollment Log/Subject Identification Code list ............65 
11.4 
Termination of the study..............................................................................................65 
11.5 
Archiving and data retention........................................................................................66 
11.6 
Audit and inspection ....................................................................................................66 
11.7 
Good Clinical Practice .................................................................................................67 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 8 of 113
12 STATISTICS ...................................................................................................................67 
12.1 
Definition of analysis sets............................................................................................67 
12.2 
General statistical considerations.................................................................................67 
12.3 
Planned efficacy analyses ............................................................................................68 
12.3.1 
Analysis of the primary efficacy variable............................................................68 
12.3.2 
Other efficacy analyses........................................................................................68 
12.4 
Planned safety analyses................................................................................................68 
12.4.1 
Safety analyses.....................................................................................................68 
12.5 
Handling of protocol deviations...................................................................................68 
12.6 
Handling of dropouts or missing data..........................................................................69 
12.7 
Planned interim analysis and data monitoring.............................................................69 
12.8 
Determination of sample size.......................................................................................69 
13 ETHICS AND REGULATORY REQUIREMENTS......................................................69 
13.1 
Informed consent .........................................................................................................69 
13.2 
Subject identification cards..........................................................................................70 
13.3 
Institutional Review Boards and Independent Ethics Committees..............................70 
13.4 
Subject privacy.............................................................................................................71 
13.5 
Protocol amendments...................................................................................................71 
14 FINANCE, INSURANCE, AND PUBLICATION.........................................................71 
15 REFERENCES ................................................................................................................71 
16 APPENDICES .................................................................................................................77 
16.1 
Modified NY criteria for ankylosing spondylitis.........................................................77 
16.2 
ASAS classification criteria for axSpA .......................................................................78 
16.3 
Corticosteroid equivalent doses...................................................................................79 
16.4 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)...............................80 
16.5 
PtGADA (NRS) ...........................................................................................................81 
16.6 
Total spinal pain NRS and nocturnal spinal pain NRS................................................82 
16.7 
Bath Ankylosing Spondylitis Functional Index (BASFI)............................................83 
16.8 
Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire................................85 
16.9 
ASAS Health Index Questionnaire..............................................................................87 
16.10 Short-Form (SF-36) Questionnaire..............................................................................92 
16.11 Tuberculosis Sample Worksheet..................................................................................98 
17 APPENDICES .................................................................................................................99 
17.1 
Protocol Amendment 1 ................................................................................................99 
17.2 
Protocol Amendment 2 ..............................................................................................101 
17.3 
Protocol Amendment 3 ..............................................................................................110 
18 DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................112 
19 SPONSOR DECLARATION ........................................................................................113 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 9 of 113
LIST OF TABLES 
Table 5-1: 
Schedule of assessments ..................................................................................23 
Table 6‒1: 
Concomitant Medications (Prior to Baseline and Study Visits) ......................31 
Table 9‒1: 
Swelling and tenderness grading .....................................................................50 
Table 10‒1: 
Anticipated serious adverse events in population independent of drug 
exposure...........................................................................................................58 
Table 10‒2: 
Laboratory measurements................................................................................59 
Table 16‒1: 
Corticosteroid equivalent doses (with reference to prednisone 10mg dose) 
(Meikle and Tyler, 1977).................................................................................79 
 
LIST OF FIGURES 
Figure 2‒1: 
ASAS classification criteria for axSpA ...........................................................17 
Figure 5-2: 
Schematic diagram...........................................................................................27 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 10 of 113
LIST OF ABBREVIATIONS 
ABA
abatacept
ADA
adalimumab
AE
adverse event
AS
ankylosing spondylitis
ASAS
Assessment of SpondyloArthritis international Society
ASDAS
Ankylosing Spondylitis Disease Activity Score
ASQoL
Ankylosing Spondylitis Quality of Life
AU
anterior uveitis
axSpA
axial spondyloarthritis
AZA
azathioprine
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BASFI
Bath Ankylosing Spondylitis Functional Index
CD20
cluster of differentiation 20
CDMS
clinical data management system
CI
clinical improvement
CII
clinically important improvement
CPMP
Committee for Proprietary Medicinal Products
CRF
Case Report Form
CRO
contract research organization
CRP
C-reactive protein
CZP
certolizumab pegol
DMARD
disease-modifying antirheumatic drug
DS
Drug Safety
ECG
electrocardiogram
eCRF
electronic Case Report Form
ePRO
electronic patient reported outcome
ES
Enrolled Set
ETN
etanercept
EudraCT
European Union Drug Regulating Authorities Clinical Trials
FAS
Full Analysis Set
FU
Follow-Up
ment
ment
portan
portan
ee for
ee for
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 11 of 113
GCP
Good Clinical Practice
GOL
golimumab
HCQ
hydroxychloroquine
HI
Health Index
HIV
human immunodeficiency virus
HLA-B27
human leukocyte antigen B27
HRQoL
health-related quality of life
ia
intra-articular
IBD
inflammatory bowel disease
ICF
informed consent form 
ICH
International Council for Harmonisation
ID
inactive disease
IEC
Independent Ethics Committee
IFX
infliximab
IGRA
Interferon-Gamma Release Assay
IMP
investigational medicinal product
IRB
Institutional Review Board
iv
intravenous(ly)
IWRS
interactive web response system
JIA
juvenile idiopathic arthritis
LFN
leflunomide
LTBI
latent tuberculosis infection
MCID
minimal clinically important difference
MI
major improvement
mNY
modified New York (classification criteria)
MRI
magnetic resonance imaging
MTX
methotrexate
nr-axSpA
nonradiographic axSpA
NRS
Numerical Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
PsA
psoriatic arthritis
PEG
polyethylene glycol
edicin
edicin
Review
Revie
ous(ly)
ous(ly)
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 12 of 113
PhGADA
Physician’s Global Assessment of Disease Activity
PR
partial remission
PtGADA
Patient’s Global Assessment of Disease Activity
Q2W
every 2 weeks (every other week)
RA
rheumatoid arthritis
RCT
randomized controlled trial
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous(ly)
SD
standard deviation
SF-36
Short-Form 36-Item Health Survey
SIJ
sacroiliac joint 
SOP
Standard Operating Procedure
SpA
spondyloarthritis
SPC
Summary of Product Characteristics
SS
Safety Set
SSZ
sulfasalazine
TB
tuberculosis
TNF
tumor necrosis factor
TNFα
tumor necrosis factor alpha
ULN
upper limit of normal
WBC
white blood cell
WD
withdrawal
VEGF
vascular endothelial growth factor
VAS
visual analog scale
sis
sis
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 13 of 113
1 
SUMMARY 
AS0007 is a multicenter, open-label, Phase 4 study to evaluate the effects of certolizumab pegol 
(CZP) on the incidence of anterior uveitis (AU) flares per year in subjects with both active axial 
spondyloarthritis (axSpA) and a history of AU by comparing the historical AU flare rate that 
occurred prior to CZP treatment with the AU flare rate occurring while under CZP treatment.
Approximately 130 subjects will be screened in Europe in order to enroll 86 subjects into the 
study.
The study duration from the start of treatment will be 96 weeks from Baseline onwards, and a 
follow-up visit will be performed at Week 104; 10 weeks after the last dose at Week 94.
The study includes 3 periods as follows: 
x Period 1 (Screening Period): 1 to 5 weeks before Baseline
Subjects will be informed about the study and sign the informed consent form (ICF). Eligibility 
will be evaluated and assessments will be performed. The Screening Period should be kept as 
short as possible but can be extended to 5 weeks if certain medications need to be washed out or 
to allow to obtain information from the subject’s ophthalmologist. For subjects who start a 
prophylactic treatment for latent tuberculosis infection (LTBI) the Screening Period can be 
extended up to 12 weeks; see Section 10.6.4.1.
x Period 2 (Treatment Period): Week 0 to Week 96 
Eligible subjects will receive a dose of CZP 400mg subcutaneously (sc) at Baseline, Week 2, and 
Week 4 followed by CZP 200mg sc every 2 weeks (Q2W) starting at Week 6 until Week 94.
All subjects will be trained at the beginning of the study on self-administration before the 
subjects start self-administration with the study drug (relative or caregiver may also perform the 
injections). The injection schedule will provide the sequence of self-administration and site visits 
including injection at the site.
x Period 3 (Follow-Up [FU] Period): 10 weeks from the final dose of study medication 
received.
All subjects will have a FU Visit at Week 104 or earlier in case of an early withdrawal (WD), 
10 weeks after the final administration of CZP administration received within the study.
A Week 48 analysis will be performed after all subjects have either completed the Week 48 Visit 
or have prematurely withdrawn prior to the Week 48 Visit. The final analysis will be conducted 
at the end of the study after all study data is locked.
The primary objective of the study will be to demonstrate the effect of CZP treatment on the 
reduction of AU flares in subjects with both active axSpA and a documented history of AU. The 
secondary objectives of the study will be to assess the effect of CZP treatment on 1) the 
reduction of AU flares in subjects with axSpA having at least 1 documented history of AU 
within 12 months prior to Baseline and 2) axSpA disease activity. Other objectives and safety 
objective are listed in Section 3.3 and Section 3.4, respectively.
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
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2 
INTRODUCTION 
2.1 
Natural history of axial spondyloarthritis  
Spondyloarthritis (SpA) is an umbrella term applied to a family of rheumatic diseases that have 
features in common with and distinct from other inflammatory arthritides, particularly 
rheumatoid arthritis (RA).
The Assessment of SpondyloArthritis international Society (ASAS) working group established 
classification criteria distinguishing 2 broad categories of SpA: peripheral and axial SpA 
(Rudwaleit et al, 2011; Rudwaleit, 2010; Rudwaleit et al, 2009b). 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, whereas axSpA 
comprises those diseases with mainly axial involvement (sacroiliac joints [SIJs] and spine), 
including ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA).
Patients with AS have definitive evidence of structural changes in the SIJ (sacroiliitis) on x-ray, 
fulfilling the modified NY (mNY) classification criteria (mNY-positive) (van der Linden, 1984);
whereas, those with nr-axSpA structural changes on conventional radiographs do not meet the 
mNY classification criteria (mNY-negative) (Appendix 16.1) (Rudwaleit et al, 2005; Dougados 
et al, 1991).
In patients with axSpA, the disease typically originates in the SIJs, then progresses to the spine. 
In the SIJs 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 SIJs 
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 C-reactive protein (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 SIJs and may fulfill the 
mNY classification 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, 2013).
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 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 15 of 113
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 
patients with chronic intestinal lesions similar to Crohn’s disease, 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, 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 
Uveitis in axial spondyloarthritis 
Uveitis is the third leading cause of blindness in developed countries. The annual incidence rate 
is estimated between 17 and 52 per 100,000 persons, and the prevalence is 38 to 714 per 
100,000 persons (Wakefield and Chang, 2005). Males and females are generally equally affected 
overall, but sex preponderance may be observed in some uveitis groups, such as a male 
predominance HLA-B27 associated uveitis and a female preponderance in juvenile idiopathic 
arthritis (JIA)-related uveitis. Uveitis may occur at any age, but most commonly affects the 
population aged between 20 and 59 years.
Uveitis is the most common extra-articular manifestation experienced by patients with axSpA 
(Boonen et al, 2002) and affects patients with both AS and nr-axSpA (Boonen et al, 2003). 
Although limited information is available regarding the overall axSpA population, 1 study 
reported the prevalence of ever experiencing a uveitis flare to be 19.3% for AS patients with 
disease duration of ≤5 years and 12.4% for nr-axSpA patients (Braun et al, 2006). Reports from 
patients with established AS suggest that approximately 40% of patients will experience 1 or 
more uveitis flares during the course of their disease (Braun and Sieper, 2007), and observational 
data sources (such as cohort studies and patient registries) have reported that 10% to 30% of 
axSpA patients classified using the ASAS criteria have a history of uveitis (Boonen et al 2003, 
Braun et al, 2011). Moreover, an attack of acute AU can be the first presenting symptom that 
leads to a diagnosis of axSpA (Braun, 2012). 
The burden of uveitis on affected patients is high, as it is commonly associated with 
photophobia, pain, and in some cases blurred vision (Braun, 2012). In axSpA patients, AU can 
range from a single flare to an episodic and recurrent course. Flares of uveitis are typically of 
sudden onset in a unilateral fashion (Callhoff et al, 2015). Regardless of disease course, in 
patients developing uveitis, impaired visual performance and reduced health-related quality of 
life is reported (Cantini et al, 2013). Acute attacks usually resolve completely with topical 
corticosteroid treatment. For axSpA patients who develop episodic and recurrent uveitis flares, 
treatment is limited. Nonsteriodal anti-inflammatory drugs (NSAIDs) may relieve symptoms for 
a short period of time (Cuirea et al, 2013), and the disease-modifying antirheumatic drugs 
(DMARDs) sulfasalazine (SSZ) and methotrexate (MTX) have been used, although available 
evidence relating to a possible decrease in flares of uveitis is limited to observational reports 
(Dougados et al, 1991; Dougados et al, 2013; Feldtkeller et al, 2000: Haibel et al, 2005). Given 
the lack of treatment options and the fact that a substantial proportion of axSpA patients are 
resistant to conventional therapies, new treatment avenues have been explored to gain control of 
uveitis flares in these patients (Haibel et al, 2013). 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 16 of 113
Analyses of uveitis flares from multiple randomized controlled trials (RCTs), in which patients 
received anti-tumor necrosis factor (TNF) therapy for the treatment of AS, have demonstrated a 
significant reduction in the incidence of acute AU flares in AS patients compared to that 
demonstrated in those patients who received placebo (Huscher et al, 2006). Furthermore, data 
from a large open-label non-controlled study demonstrated a significant reduction in the rate of 
AU flares following adalimumab (ADA) treatment of AS patients (Kobelt et al, 2004). A UCB 
study by Van Denderen et al, 2014, a pooled data analysis (Huscher et al, 2006), and a recent 
review (Rosenbaum et al, 2014) have suggested that the monoclonal antibodies ADA and 
infliximab (IFX) are equally effective in reducing AU flares, and are superior to etanercept 
(ETN) in this regard. However, at present, there are no RCT data available demonstrating the 
efficacy of anti-TNF in the reduction of uveitis flares in an axSpA population.
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 
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, 1984), 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, 2009b; Rudwaleit et al, 2009c). These 
criteria establish standards that apply to patients with or without radiographic sacroiliitis, 
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 
magnetic resonance imaging [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 SIJ inflammation or radiographic evidence of sacroiliitis meeting the mNY 
classification criteria (Rostom, 2010).
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 17 of 113
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 (classification criteria); MRI=magnetic resonance imaging; 
NSAID=nonsteroidal anti-inflammatory drug; SpA=spondyloarthritis. 
Source: Rudwaleit et al, 2009c 
2.4 
Current management of axial spondyloarthritis and uveitis 
Based on the current treatment recommendations developed by ASAS and the European League 
Against Rheumatism for axSpA, first-line therapy consists of NSAIDs and nonpharmacologic 
treatment, such as patient education and regular exercise/physiotherapy (Braun et al, 2011). 
Nonsteroidal anti-inflammatory drugs usually have a rapid initial effect for the symptoms pain 
and stiffness of axSpA (Poddubnyy et al, 2012; Poddubnyy et al, 2013), but many patients lose 
symptomatic response and structural damage often progresses despite their use. Conventional 
DMARDs (eg, MTX and SSZ) have limited efficacy in axial disease but may benefit patients 
with peripheral joint disease (Braun et al, 2006; Haibel et al, 2005; Haibel et al 2007). 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, ADA, ETN, IFX, and golimumab [GOL]) are currently the only 
effective and approved treatment options. 
Uveitis can be caused by infectious and noninfectious etiologies. The precise diagnosis is 
crucially important to establish the most accurate therapy. 
For most noninfectious uveitis, the control of inflammation is the key to treatment success. The 
normal option is a stepladder approach and the treatment includes local corticosteroids, systemic 
corticosteroids, and systemic immune modulators, often sequentially starting with topical 
therapy. Noninfectious uveitis is often associated with other systemic conditions, such as 
HLA-B27-related spondyloarthropathies, inflammatory bowel disease, JIA, Behcet’s Disease, 
and sarcoidosis. The treatment of systemic symptoms may also improve the ocular inflammation.
OR
SpA features
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• Dactylitis
• Psoriasis
• Crohn’s/colitis
• Good response to NSAIDs
• Family history for SpA
• HLA-B27
• Elevated CRP
*Sacroiliitis on imaging
N = 649 patients with back pain
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Imaging arm alone
Sensitivity: 66.2%; Specificity: 97.3%
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 18 of 113
Systemic immunomodulatory medications used for ocular inflammatory conditions include 
conventional immunosuppressive agents and biologic response modifiers. The agents include 
antimetabolites, inhibitors of T-cell signaling, and alkylating agents. 
Biologic therapy can be an alternative in patients with inadequate response to or intolerance of 
conventional immunotherapy. Biologicals were developed and approved to treat systemic 
inflammatory diseases or to prevent organ transplantation rejection. Several biologicals are 
approved for the treatment of axSpA, however none have been approved in the USA or the EU 
specifically for the treatment of uveitis but have been used off-label to treat uveitis or ocular 
inflammation.
2.5 
Rationale 
Noninfectious AU is characterized by a genetic disposition expressed by positive HLA-B27. 
Spondyloarthritis (SpA) represents the most frequent extra-ocular manifestation observed in 
patients with HLA-B27 associated AU. The prevalence of SpA in subjects with HLA-B27 
positive AU reportedly ranges from 13% to 58.3% (Monnet et al, 2004; Rosenbaum, 1989). 
The prevalence of AU is variable between the different types of SpA. Considering the 3 most 
frequent SpA (AS, psoriatic arthritis [PsA], and IBD-associated SpA), it is generally understood 
that in patients with AS, there is a greater frequency of AU in patients with AS compared to the 
other 2 disorders. Anterior uveitis at onset or complicating the disease course has been reported 
in 33% of patients with AS, while the reported percentages are lower in PsA and IBD-associated 
SpA (Zeboulon et al, 2008). Therefore, AU represents the most frequent extra-articular 
manifestation and is often also the starting point to recognizing the spinal involvement and AS.
The extra-articular manifestations in AS are seen in more than one-third of the AU patients and, 
within this set of manifestations, uveitis represents the largest group with 51% of the 
extra-articular manifestations. This means that 20% of the axSpA patients are confronted with 
uveitis at some point during their lifetime.
While uveitis flares are usually infrequent and are managed with topical therapies, an important 
subset has frequent treatment refractory flares.
A significant amount of data exists for ADA and IFX for the treatment of uveitis and the 
prevention of flares, but neither agent is approved (ADA in Phase 3) at the moment for this 
indication. Although CZP belongs to the same group of agents, less data are available.
Certolizumab pegol, a PEGylated Fragment crystallizable-free anti-TNF, has been shown to 
improve spinal and extra-articular manifestations, such as enthesitis and peripheral arthritis, in 
patients with axSpA (including both AS and nr-axSpA patients) (Landewé et al, 2014).
Emerging data from a retrospective case series indicate a treatment effect of CZP in active 
refractory uveitis (Myasoedova et al, 2010) and justifies further research. Further data are 
required to determine the effectiveness of CZP in reducing the incidence of uveitis flares in 
axSpA patients, an important facet of disease symptomatology (Olivieri et al, 2013).
AS0007 will investigate the effect of CZP treatment on the frequency of AU flares in subjects 
with axSpA.
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 19 of 113
3 
STUDY OBJECTIVE(S) 
The following key definition is provided as a reference for understanding the study objectives 
and is used throughout the protocol.
A flare is defined as being a new episode of AU that, based on the judgment of an 
ophthalmologist, requires specific treatment. A flare is considered a new episode if a gap of at 
least 3 months occurs between 2 flares.
3.1 
Primary objective 
The primary objective of the study will be to demonstrate the effect of CZP treatment on the 
reduction of AU flares in subjects with active axSpA and a documented history of AU.
3.2 
Secondary objectives 
The secondary objectives of the study will be to assess the effect of CZP treatment on:
x The reduction of AU flares in subjects with active axSpA having at least 1 documented 
history of AU within 12 months prior to Baseline
x AxSpA disease activity
3.3 
Other objectives 
The other objectives of the study will be to assess the effect of CZP treatment on:
x Physical function
x Signs and symptoms of axSpA
 Morning stiffness
 Fatigue
 Extra-articular manifestations of axSpA 
x Duration and severity of AU flares
3.4 
Safety objective 
The safety objectives of the study will be to evaluate the safety and tolerability of CZP therapy.
4 
STUDY VARIABLES 
4.1 
Efficacy variables 
4.1.1 
Primary efficacy variable 
The primary efficacy variable will be the count of distinct episodes of AU flares during the 
Treatment Period. 
4.1.2 
Secondary efficacy variables 
The following secondary efficacy variables will be assessed at Week 48 and Week 96:
x Number of AU flares per 100 patient-years in subjects with active axSpA and a history of 
AU
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 20 of 113
x Number of AU flares per 100 patient-years in subjects with active axSpA and at least 1 AU 
episode within 12 months prior Baseline
x Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
x Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
x Assessment of ASAS 20, 40, 5/6, and partial remission (PR) response rates
x Change from Baseline in tender and swollen joint count (44 joint count); Physician’s Global 
Assessment of Disease Activity (PhGADA).
x Change from Baseline in the respective components of the ASAS response criteria, assessed 
by:
 Patient’s Global Assessment of Disease Activity (PtGADA)
 Pain assessment (total spinal pain Numerical Rating Scale [NRS])
 Function (represented by Bath Ankylosing Spondylitis Functional Index [BASFI])
 Inflammation (the mean of the BASDAI questions 5 and 6 concerning 
)
4.1.3 
Other efficacy variables 
The following other efficacy variables will be assessed at the timepoints indicated in Table 5-1:
x Duration of AU flares 
x Severity of AU flares
x Change from Baseline in ASDAS
x Change from Baseline in BASDAI
x ASAS 20, 40, 5/6, and PR response rates
x Change from Baseline in tender and swollen joint count (44 joint count), PhGADA.
x Change from Baseline in the respective components of the ASAS criteria, assessed by:
 PtGADA
 Pain assessment (total spinal pain NRS)
 Function (represented by BASFI)
 Inflammation (the mean of the BASDAI questions 5 and 6 concerning 
)
x Change from Baseline in ASDAS disease activity (clinical improvement [CI], major 
improvement [MI], inactive disease [ID], clinically important improvement [CII]), and 
BASFI) (including Weeks 48 and 96)
x Change from Baseline in 
 (NRS) (from BASDAI) (including Weeks 48 and 96)
x Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) (including 
Weeks 48 and 96)
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 21 of 113
x Change from Baseline in ASAS Health Index (HI) questionnaire (including Weeks 48 and 
96)
x Change from Baseline in Short-Form 36-Item Health Survey (SF-36) (including Weeks 48 
and 96)
x Number of IBD exacerbations
x Number of psoriasis exacerbations (in subjects with concurrent psoriasis)
4.2 
Safety variables 
4.2.1 
Secondary safety variable 
The secondary safety variable to be assessed is treatment-emergent adverse events (TEAEs).
4.2.2 
Other safety variables 
The following other safety variables to be assessed are:
x Blood pressure
x Physical examination
x Clinical laboratory values (hematology, biochemistry, and urinalysis)
5 
STUDY DESIGN 
5.1 
Study description 
AS0007 is a multicenter, open-label, Phase 4 study to evaluate the effect of CZP on the incidence 
of AU flares per year in subjects with both active axSpA and a history of AU by comparing the 
historical AU flare rate that occurred prior to CZP treatment with the AU flare rate occurring 
while under CZP treatment. 
The study duration from the start of treatment will be 96 weeks from Baseline onwards, and a FU 
Visit will be performed at Week 104, 10 weeks after the final dose. A schedule of study 
assessments is provided in Table 5-1.
The study includes 3 periods as follows: 
x Period 1 (Screening Period): 1 to 5 weeks before Baseline
Subjects will be informed about the study and sign the ICF. Eligibility will be evaluated and 
assessments will be performed as listed in Table 5-1. The Screening Period should be kept as 
short as possible but can be extended to 5 weeks if certain medications need to be washed out or 
to allow to obtain information from the subject’s ophthalmologist. For subjects who start a 
prophylactic treatment for LTBI, the Screening Period can be extended up to 12 weeks (see 
Section 10.6.4.1).
x Period 2 (Treatment Period): Week 0 to Week 96 
Eligible subjects will receive a dose of CZP 400mg sc administered at Baseline, Week 2, and 
Week 4 followed by CZP 200mg sc Q2W (starting at Week 6 until Week 94).
All subjects will be trained at the beginning of the study on self-administration before the 
subjects start with self-administration (relative or caregiver may also perform the injections). The 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 22 of 113
injection schedule will provide the sequence of self-administration and site visits including 
injection at the site.
x Period 3 (FU Period): 10 weeks from the final dose of study medication received.
All subjects will have a FU Visit at Week 104 or earlier in case of an early WD, 10 weeks after 
the final CZP administration received within the study.
A Week 48 analysis will be performed after all subjects have either completed the Week 48 Visit 
or have prematurely withdrawn prior to the Week 48 Visit. The final analysis will be conducted 
at the end of the study after all study data is locked.
5.1.1 
Study duration per subject 
For each subject, the study will last a maximum of 109 weeks, as follows:
x Up to 5 weeks of Screening Period (see Section 10.6.4.1 for details on an extended Screening 
Period of 12 weeks)
x A Treatment Period of 96 weeks
x A FU Visit at Week 104
The end of the study is defined as the date of the last study FU Visit.
5.1.2 
Planned number of subjects and sites 
Approximately 130 subjects will be screened in order to enroll 86 subjects into the study.
The estimated recruitment period will be approximately 12 months. This takes into account an 
estimate of a 35% screen failure rate between Screening and Baseline. Prematurely discontinued 
randomized subjects will not be replaced. 
Subjects are planned for enrollment at approximately 20 to 30 sites.
5.1.3 
Anticipated regions and countries 
The study will be conducted in Europe.
5.2 
Schedule of study assessments 
The Schedule of Assessments is shown in Table 5-1. A study schematic is presented in 
Figure 5-2.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 23 of 113
Table 5-1: 
Schedule of assessments 
Study Period
Period 1 
(Screening)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
36
48
60
72
84
96/ 
WD
104
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Written informed 
consentb
X
Assessments for 
inclusion/exclusion 
criteria
X
X
Demographic data
X
Medical history 
(including axSpA 
history, and tobacco 
use) and 
concomitant diseases 
X 
Prior and
concomitant 
medicationc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Uveitis history
X 
Uveitis flare 
evaluation
 
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examinatione
X 
X
X
X
X
X
X
X
X
X
X
X
X
Extra-articular 
assessmentsf
X
X
X
X
X
X
X
X
X
X
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
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Study Period
Period 1 
(Screening)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
36
48
60
72
84
96/ 
WD
104
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Hematology/ 
urinalysis/
biochemistry/ 
Xg 
X
X
X
X
X
X
X
X
X
X
X
CRP 
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testingh
X 
X
X
X
Chest x-rayi
X 
TB testj
X 
X
X
TB questionnaire
X 
X
X
X
X
X
X
X
X
X
MRI (nr-axSpA 
subjects only)k
X
X-ray (AS subjects 
only)l
X
BASDAI
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
ASQoL
X
X
X
X
X
X
X
X
X
X
X
ASAS HI 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
X
PtGADA
X
X
X
X
X
X
X
X
X
X
X
X
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 25 of 113
Study Period
Period 1 
(Screening)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
36
48
60
72
84
96/ 
WD
104
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Total and nocturnal
spinal pain
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
PhGADA
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
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc 
injectionsm
X
X
X
X
X
X
X
X
X
X
X
Schedule 
appointment for next 
visit
X
X
X
X
X
X
X
X
X
X
X
X
X
AE=adverse event; AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; ASQoL=Ankylosing Spondylitis Quality of Life; 
axSpA= axial spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; 
BL=Baseline; CRP=Creactive protein; FU=Follow-up; HI=Health Index; HLA-B27= human leukocyte antigen B27; IBD=inflammatory bowel disease; 
IWRS=Interactive Web Response System; LTBI=latent tuberculosis infection; mNY=modified New York (classification criteria); MRI=magnetic resonance 
imaging; nr-axSpA=nonradiographic axSpA; PhGADA=Physician’s Global Assessment of Disease Activity; PtGADA=Patient’s Global Assessment of Disease 
Activity; Q2W=every 2 weeks (every other week); sc=subcutaneous(ly); SF-36=Short-Form 36-Item Health Survey; SIJ=sacroiliac joint; TB=tuberculosis; 
WD=Withdrawal  
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 26 of 113
Study Period
Period 1 
(Screening)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
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48
60
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Visit
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5
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7
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9
10
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14
a For subjects with LTBI who initiate a prophylactic treatment and need to have 8 weeks of  prophylactic treatment prior to randomization, the Screening Period 
can be extended to 12 weeks. For other subjects, the Screening Period should be kept as short as possible, but can be up to 5 weeks if certain medications need 
to be washed out or to allow to obtain information from the subjects’ ophthalmologist.
b Informed consent: prior to any study activities, subjects will be asked to read and sign the informed consent form.
c Past medications will recorded at Screening. Concomitant medications will be recorded at all other visits.
d Pulse rate, systolic and diastolic blood pressures, and temperature are to be measured at Screening and Baseline, thereafter systolic and diastolic blood 
pressures are to be measured. 
e Weight is to be measured at Screening, Baseline, Week 48, and at completion at Week 96/WD Visit. Height will be measured at the Baseline Visit only.
f Extra-articular assessments includes the number of IBD exacerbations and number of psoriasis exacerbations (in subjects with concurrent psoriasis)
g Testing to rule out hepatitis B core antibody, hepatitis B surface antigen, hepatitis B surface antibody, antibodies to hepatitis C, and antibodies to human 
immunodeficiency virus at Screening only. Testing for HLA-B27 at Screening, only if not performed before.
h Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and urine dipstick testing at Baseline and Week 96/WD Visit 
and the FU Visit (10 weeks after the final dose of study drug). 
i Chest x-ray used for screening must have been done within 3 months prior to the 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). If no chest x-ray is available within the 3 months prior to the Screening 
Visit, the x-ray can be done during the Screening Period.
j QuantiFERON TB GOLD test. The TB tests will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for subjects with previously negative 
TB test result.
k For subjects with nr-axSpA, an MRI of the SIJs is to be performed during the Screening Period. An MRI performed ≤3 months prior to the Baseline Visit may 
be used as the Baseline. An MRI assessment is not needed for patients with AS.
l AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting the mNY classification criteria according to the Investigator. If not 
available, this x-ray is to be taken during the Screening Period. If an x-ray was performed prior to the Screening Visit and the mNY classification criteria were 
met, the x-ray is not to be repeated.
m Onsite study drug administration will occur after all other visit assessments are completed and laboratory samples are drawn. Study drug injections will occur at
home Q2W on Weeks 6, 8, and 10, 14 to 22, 26 to 30, 34, 38 to 46, 50 to 58, 62 to 70, 74 to 82, and 86 to 94. At all visits, an even number of syringes (2 per 
box) will be assigned (eg, at Week 4 syringes will be assigned for Weeks 6, 8, and 10; 1 syringe will be returned by the subject at Week 12).
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 27 of 113
5.3 
Schematic diagram 
Figure 5-2: Schematic diagram 
axSpA=axial spondyloarthritis; CZP=certolizumab pegol; LD=loading dose; Q2W=every 2 weeks
Open-label Phase (94 weeks) 
Active axSpA 
subjects with a 
history of 
Anterior Uveitis 
Follow-up 
(10 weeks) 
Screening Phase 
(1 – 5 weeks) 
CZP 200 mg Q2W 
LD 
CZP 400mg 
at Week 0, 2 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 28 of 113
5.4 
Rationale for study design and selection of dose 
The aim of the study is to evaluate the flare rate of AU before the start of CZP treatment 
compared to that of a period with CZP treatment. Since the occurrence of flare is both subject 
and disease specific, each subject should act as his/her own control. Because an untreated 
uveitis flare can cause severe eye complication, it was deemed necessary to treat all subjects 
with an active drug.
Therefore, 1 treatment arm with 1 set of subjects is deemed the right approach to allow for 
the comparison of the history of flare occurrence with the flare occurrence on a biological 
treatment in the same subjects. The dose of CZP used in this study is the same as per label to
treat axSpA subjects, which has been shown to be 
 and effective for reducing the main 
axSpA symptoms.
6 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1 
Inclusion criteria 
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved 
written Informed Consent form is signed and dated by the subject.
2. Subject is considered reliable and capable of adhering to the protocol (eg, able to 
understand and complete diaries), visit schedule, or medication intake according to the 
judgment of the Investigator.
3. Subject is at least 18 years old at the 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 or contraception methods that are considered as at least as safe for 
contraception). Abstinence only is not an acceptable method. Subjects must agree to use 
adequate contraception during the study and for at least 5 months (in accordance with the 
Summary of Product Characteristics [SPC]) after the last dose of study treatment. Male 
subjects must agree to ensure that they or their female partner(s) use adequate 
contraception during the study and for at least 5 months (in accordance with the SPC), 
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 criteria (according to Appendix 16.2).
6a. Subjects must have active disease at Screening as defined by
 BASDAI score ≥ 4
 Spinal pain ≥ 4 on a 0 to 10 NRS (from BASDAI item 2)
 Nr-axSpA subjects must either have CRP > upper limit of normal (ULN) and/or 
current evidence of sacroiliitis on MRI (no confirmation by central reading) as 
defined by ASAS criteria
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 29 of 113
 AS subjects must have evidence of sacroiliitis on x-ray meeting the mNY 
classification criteria according to the Investigator
7.
Subjects must have a documented history of AU diagnosed by an ophthalmologist and 
have at least 2 AU flares in the past, of which at least 1 AU flare was in the last 
12 months prior to Baseline. 
8. Subjects must be HLA-B27 positive (if known prior to Screening, no additional testing is 
to be performed; if unknown, testing is to be performed at Screening and checked at 
Baseline).
9. Subjects must have been intolerant to or had an inadequate response 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. The subject has previously participated in this study or has previously received CZP 
treatment in or outside of another clinical study. However rescreening is possible if 
prophylactic treatment for LTBI was to be given but the Screening Period exceeded the 
12 weeks.
2. The subject has participated in another study of an investigational medicinal product 
(IMP) (or a medical device) within the previous 3 months or is currently participating in 
another study of an IMP (or a medical device).
3. The subject has a history of chronic alcohol or drug abuse.
4. The 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. The subject has a known hypersensitivity to any components of CZP or a history of an 
adverse reaction to polyethylene glycol (PEG).
Axial SpA-disease-related exclusions
6. Subjects must not have any other inflammatory arthritis (eg, RA, systemic lupus 
erythematosus, sarcoidosis, or fibromyalgia).
7. Subjects must not have a secondary, noninflammatory condition that, in the Investigator’s 
opinion, is symptomatic enough to interfere with evaluation of the effect of study drug on 
the subject’s primary diagnosis of axSpA.
Ophthalmic exclusion criteria
8. Any history of uveitis (eg, posterior, panuveitis) except for AU associated with axSpA.
9a. Any condition or complicating factor that may interfere with the AU assessment, for 
example:
a. History of cataract surgery within 6 months prior to Baseline
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 30 of 113
b. Corneal or lens opacity
c. Proliferative or severe nonproliferative diabetic retinopathy or clinically significant 
macular edema due to diabetic retinopathy
d. Neovascular/wet age-related macular degeneration
e. History of scleritis
f. History of intraocular surgery, with the exception of phacoemulsification
10. Subject has Retisert® or Iluvien® (glucocorticosteroid implant) within 3 years prior to the 
Baseline Visit or has had complications related to the device. Subject has had Retisert or 
Iluvien (glucocorticosteroid implant) removed within 90 days prior to the Baseline Visit 
or has had complications related to removal of the device.
11. Subject has received intraocular or periocular corticosteroids within 90 days prior to the 
Baseline visit.
12. Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the 
Baseline Visit.
13. Subject on cyclophosphamide within 30 days prior to the Baseline Visit.
14. Subject has received intravitreal MTX within 90 days prior to the Baseline Visit.
15. Subject has received intravitreal anti-vascular endothelial growth factor (VEGF) therapy:
a. Within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin®
(bevacizumab)
or
b. Within 60 days of the Baseline visit for anti-VEGF Trap Zaltrap® (aflibercept)
Prior medications exclusions 
16a. Subjects must not have used the following medications in the manner as detailed by the 
exclusion criteria in Table 6‒1.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 31 of 113
Table 6‒1: 
Concomitant Medications (Prior to Baseline and Study Visits) 
Drug class
Dose
Exclusion criteria
Analgesics (including, but not 
limited to acetaminophen, 
paracetamol, NSAIDs, opiates or 
combinations thereof )
Any dose
PRN doses of an analgesic should 
not be used within 24 hours of 
Baseline or any other Study Visit. 
Stable doses of analgesics 
(including narcotics) are to be 
maintained throughout the study. 
NSAIDs/cyclooxygenase 2 
(COX 2) inhibitors
Any dose regimen
PRN doses of an NSAID should 
not be used within 24 hours of 
Baseline or any other Study Visit.
Any change in stable dose in the 
14 days prior to the Baseline Visit 
is exclusionary.
Stable doses of NSAIDs are to be 
maintained throughout the study.
Oral corticosteroids (for AU 
only)
Maximum allowed ≤10mg 
daily total prednisone 
equivalenta
Any change in stable dose in the 
28 days prior to the Baseline Visit 
is exclusionary.
Oral corticosteroid tapers of less 
than 14 days used to treat other 
indications (asthma exacerbation, 
contact dermatitis, etc.) during the 
study are allowed as long the 
maximum daily dose is ≤20mg
Intramuscular (im) 
corticosteroids
Any dose
Use in the 28 days prior to the 
Baseline Visit is exclusionary.
Intra-articular (ia) corticosteroids
Any dose
Use in the 28 days prior to the 
Baseline Visit is exclusionary. 
Intravenous (iv) corticosteroids
Any dose
Any exposure during study is not 
allowed. 
Intra-articular hyaluronic acid 
Any dose 
Use in the 28 days prior to the 
Baseline Visit is exclusionary. 
Disease-modifying antirheumatic 
drugs (DMARDs):
sulfasalazine (SSZ) and/or 
hydroxychloroquine (HCQ) 
and/or methotrexate (MTX) 
and/or leflunomide (LFN) and/or 
azathioprine (AZA)
Maximum allowed:
SSZ ≤3g daily
HCQ ≤400mg daily
MTX ≤25mg weekly
AZA ≤150mg daily
LFN ≤20mg daily
Use initiated in and/or any change 
in the dose regimen in the 28 days 
prior to the Baseline Visit is 
exclusionary.
DMARDs dose should be kept 
stable throughout the study except 
for reasons of intolerance, where 
the DMARD dose may be 
decreased.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 32 of 113
Table 6‒1: 
Concomitant Medications (Prior to Baseline and Study Visits) 
Drug class
Dose
Exclusion criteria
DMARDs:
cyclosporine, cyclophosphamide, 
mycophenolic acid, apremilast
Any dose
Use within 28 days prior to the 
Baseline Visit is exclusionary.
Must not be started during the 
study.
Biologicals:
infliximab (IFX)
adalimumab (ADA)
etanercept (ETN)
golimumab (GOL)
Any dose
For IFX, ADA, and GOL, any use 
within the 3 months prior to the 
Baseline Visit.
For ETN, use within the 28 days 
prior to the Baseline Visit.
Only 1 previous biological is 
allowed.
Other biologicals eg,
abatacept (ABA)
anti CD20
tocilizumab
ustekinumab
secukinumab
certolizumab pegol (CZP)
Any dose
Any exposure history.
Must not be started during the 
study.
AU= anterior uveitis; DMARD=disease modifying antirheumatic drug; NSAID=nonsteroidal anti-inflammatory 
drug; PRN=as needed; STJ= swollen and tender joint
a A table of corticosteroid equivalent doses is provided in Appendix16.3, Table 16‒1.
Previous clinical studies and previous biological therapy exclusions
17. Subjects must not have received any nonbiological therapy for axSpA not listed in 
Table 6‒1 within or outside of a clinical study in the 3 months or within 5 half lives prior 
to the Baseline Visit (whichever is longer).
18. Subjects must not have received any experimental biological agents (defined as those 
agents unlicensed for use in axSpA in the EU or the USA).
19. Subjects must not have received previous treatment with a PEGylated compound that 
resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
20. Subjects must not have been exposed to more than one TNF antagonist prior to the 
baseline visit and may not be a primary failure to any TNF antagonist therapy (defined as 
no response within the first 12 weeks of the TNF antagonist treatment).
Medical history exclusions
21. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 5 months (or longer, if required by local regulation) following the final 
dose of the investigational product.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 33 of 113
22. Subjects with a history of chronic or recurrent infections, excluding uveitis (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).
23. Subjects with a history of herpes zoster infection within 6 months prior to the Baseline 
Visit.
24. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, 
or LTBI.
a. Known TB infection whether present or past is defined as:
 Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extrapulmonary)
 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.
c. Latent TB infection (unless appropriate prophylaxis is initiated prior to study 
treatment and continued to completion of prophylaxis) is defined as:
 The absence of signs, symptoms (ie, evidence of organ-specific involvement), or 
physical findings suggestive of TB infection with a positive interferon-gamma release 
assay (IGRA; 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 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 Study Physician, if LTBI 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. 
Note: If available, respiratory or other specimens must also be smear and culture 
negative for TB (Centers for disease control diagnosis of LTBI, 
http://www.cdc.gov/TB/topic/testing/default.htm)
Detailed information on TB definition, clinical signs, diagnosis, documentation, and 
treatment will be available in this protocol.
25. Subjects with current acute or chronic viral hepatitis B or C or with human 
immunodeficiency virus (HIV) infection.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 34 of 113
26. Subjects with current or a history of active infection with Histoplasma, Coccidiodes,
Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, or 
Aspergillus.
27. Subjects with a history of an infected joint prosthesis at any time.
28. 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).
29. 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).
30. Subjects with a history of a lymphoproliferative disorder, including lymphoma or current 
signs and symptoms suggestive of lymphoproliferative disease.
31. 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).
32. Subjects with Class III or IV congestive heart failure as per the New York Heart 
Association 1964 criteria.
33. Subjects with a history of, or suspected, demyelinating disease of the central nervous 
system (eg, multiple sclerosis or optic neuritis).
34. 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.
35. Subjects with a history of or a current, as determined by the Investigator, severe, 
progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, 
cardiac, or neurological disease.
36. Subjects with significant laboratory abnormalities at Screening including but not limited 
to:
 Liver function tests >2.0 x ULN
 Estimated Glomerular Filtration Rate<60 mL/min/1.732 as measured by Chronic 
Kidney Disease Epidemiology Collaboration (Levey et al, 2009) 
 White blood cell (WBC) count <3.0x109/L.
37. Subjects with any other condition which, in the Investigator’s judgment, would make the 
subject unsuitable for inclusion in the study
6.3 
Withdrawal criteria 
Subjects will be free to withdraw from the study at any time, without prejudice to their 
continued care.
At the Investigator’s discretion, the subject may be withdrawn from the study at any time (eg, 
to receive alternative treatment for the disease).
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 35 of 113
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 regulatory agency requests withdrawal of the subject.
7. The Sponsor requests withdrawal of the subject for safety reasons.
8. 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 LTBI, no prophylactic treatment was initiated (see 
Section 10.6.4).
9. Subject who prematurely discontinues treatment for latent TB or, in the opinion of the 
Investigator or Sponsor, is noncompliant with anti̻TB therapy, must be withdrawn.
Once withdrawn from study treatment, subjects must return for a Withdrawal Visit and 
perform all assessments as defined for the W96/WD Visit in Table 5-1, and complete a final 
FU Visit, 10 weeks after the last dose of study medication is administered.
Investigators should attempt to obtain information on subjects in the case of withdrawal or 
discontinuation. For subjects considered 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 (CRF) 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.
7 
STUDY TREATMENT(S) 
7.1 
Description of investigational medicinal product(s) 
For the purpose of the protocol IMP refers to CZP. 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 site will be adapted to the recruitment capacity of 
that site and to the expiry date of the IMP and will be managed by the interactive web 
response system (IWRS).
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 36 of 113
Certolizumab pegol is an engineered humanized monoclonal antibody Fab´ fragment with 
specificity for human TNFα, manufactured in E. coli. The antibody fragment is subsequently 
purified and conjugated with high molecular weight PEG (40kDa). 
Certolizumab pegol will be supplied as a sterile, clear, colorless to-slightly yellow liquid 
solution with a pH of approximately 4.7 in 1mL single-use glass prefilled syringe with a 
thin-walled needle for sc injection. Each syringe will contain 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.
7.2 
Treatment(s) to be administered 
The IMPs will be administered as sc injections into either the lateral abdominal wall or the 
upper outer thigh. Each injection should be administered at a separate injection site, and 
rotation between the injection sites should be observed. Before injection, the PFS should be 
brought to room temperature. Certolizumab pegol will be administered as 400mg at Baseline 
and Weeks 2 and 4 followed by 200mg Q2W (starting at Week 6 until Week 94). Subjects 
will be trained by the qualified, designated, site personnel and be provided with written 
instructions on the correct injection technique. Once the subject is trained at the start of the 
study the subject will have the opportunity to self-inject IMP. Site personnel must investigate 
whether the subjects have adequate storage conditions at home and are willing and able to 
perform the injection of IMP. Subjects who opt for self-administration may also request that 
a designated caregiver/family member administers the IMP. This person must attend all 
protocol-required training and be tested and judged as capable of administering the study 
medication to the subject.
7.3 
Packaging 
Certolizumab pegol is packaged and labeled according to Good Manufacturing Practice 
guidelines and applicable laws or regulations. It is suitably packaged in such a way as to 
protect the IMP from deterioration during transport and storage. 
7.4 
Labeling 
Certolizumab pegol packaging will be labeled in accordance with the current International 
Council for Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good 
Manufacturing Practice and will include any locally required statements. If necessary, labels 
will be translated into the local language.
7.5 
Handling and storage requirements 
7.5.1 
Storage at the site 
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the 
site. The IMP stored by the Investigator should be kept in a secured area with limited access.
The IMP containers should be under conditions as detailed in the IMP manual. In case an 
out-of-range temperature is noted, it must be immediately communicated within the IWRS 
and UCB as described in the IMP manual before further use of the IMP.
Appropriate storage conditions (storage of CZP is to be done at 2 to-8ºC) must be ensured 
and completion of a temperature log in accordance with local requirements must be done on 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 37 of 113
a regular basis (eg, once a week), but at least once per working day showing minimum and 
maximum temperatures reached over the time interval. In case of an out of range 
temperature, based on discussion with a UCB Quality Assurance representative, the Drug 
Supply Coordinator will then provide the site with instructions regarding use of the IMP and 
adjust the status of the IMP as needed in the IWRS.
The Investigator (or designee) will instruct subjects to store the IMP following the 
instructions on the label.
7.5.2 
Storage at the subject’s home 
The Investigator (or designee) will instruct the subject how to handle the IMP during 
transport and how to store the IMP as per the label. Specific emphasis on the transport from 
site to home is required and instructions on the use of cold bags for CZP syringes must be 
followed. The subject is instructed to put the syringes as quickly as possible into his/her 
refrigerator. 
In the case of a malfunctioning refrigerator or damaged or lost syringes, the subject must 
inform the site immediately and new syringes will be provided.
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 return or destruction.
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.
7.7 
Procedures for monitoring subject compliance 
At each on-site visit after IMP is dispensed, subjects must return all used and unused IMP to 
the site. 
Drug accountability must be recorded on the drug accountability form.
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
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 38 of 113
7.8 
Concomitant medication(s)/treatment(s) 
7.8.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study for uveitis:
x 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 (see Table 6‒1).
 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.
The following concomitant medications are permitted during the study for axSpA:
x NSAIDs/cyclooxygenase 2 (COX-2) inhibitors
 Stable doses of analgesics established at Baseline (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. 
x 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 (see Table 6‒1).
 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) administration of corticosteroids is 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) 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.
x Disease-modifying antirheumatic drugs (DMARDs) (only SSZ and/or 
hydroxychloroquine [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 DMARDs 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
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 39 of 113
x 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:
x Corticosteroids (administered oral, ia, or iv) are permitted only as described in 
Section 7.8.1. Intramuscular corticosteroids and SIJ ia corticosteroid injections are not 
permitted.
x Hyaluronic acid may be used as ia injection in the knee only.
x Specific DMARDs (cyclosporine, cyclophosphamide, mycophenolic acid, apremilast). 
Biologicals (TNF antagonists: IFX, ADA, ETN, GOL; abatacept [ABA]; CZP; 
Rituximab or other anticluster of differentiation 20 [anti-CD20] antibodies; tocilizumab; 
ustekimumab; tofacitinib; or any other biological response modifiers that are not licensed 
for the treatment of AS or axSpA).
x All iv bisphosphonates (zoledronic acid, ibandronate, pamidronate) are excluded.
x 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 
electronic Case Report Form (eCRF).
7.8.3 
Rescue medication 
A rescue medication is any medication other than prohibited medication that is used to treat 
axSpA or uveitis. The use of rescue medication is allowed during Screening through 
Week 96/WD Visit, except under the conditions noted in Section 7.8.2.
7.9 
Blinding 
This will be an open-label study; therefore, blinding is not applicable.
7.10 
Enrollment into treatment and numbering of subjects 
An IWRS will be used for assigning CZP treatment to eligible subjects. The IWRS will 
generate individual assignments for subject kits of IMP, as appropriate, according to the visit 
schedule.
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 40 of 113
To enroll a subject into the study (Visit 1), the Investigator or designee will contact the 
IWRS 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 communications between the Investigator or 
designee and the IWRS regarding a particular subject. Subject numbers and kit numbers will 
be tracked via the IWRS. 
To enroll a subject into the Treatment Phase, the Investigator or designee will contact the 
IWRS and provide brief details about the subject to be enrolled. The IWRS will 
automatically allocate kit numbers to the subject based on the subject number during the 
course of the study.
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 FU Period of 10 weeks after the last dose of the study drug. For 
Week 2 to Week 96 the visit window is ±3 days from the actual date in Weeks from the 
initial administration of IMP (Week 0). For the FU Visit a window of 1-2 weeks is 
acceptable.
8.1 
Visit 1 (Week -5 to -1) Screening  
Prior to any study activities, subjects will be asked to read and sign an informed consent form 
(ICF) for participation in the study. All ICFs will have been approved by an IEC/IRB and 
will 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: 
x Confirm informed consent
x Review inclusion/exclusion criteria
x Demographic data (includes date of birth, gender, race/ethnicity)
x Washout of excluded medications (3 months for TNFs)
x Significant past medical and procedure history (including tobacco use) and concomitant 
disease (including axSpA history) 
x Prior and concomitant medication
x Review of the uveitis history containing all documented UA 
x Vital signs (pulse rate, systolic and diastolic blood pressures, and temperature)
x Physical examination (including weight)  and extra-articular assessment (including the 
number of IBD exacerbations and number of psoriasis exacerbations [in subjects with 
concurrent psoriasis])
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 41 of 113
x Hematology, biochemistry, and urinalysis for clinical laboratory values 
x Hepatitis-associated disease markers assessment:
 Hepatitis B core antibody (HBc-Ab)
 Hepatitis B surface antigen (HBs-Ag)
 Hepatitis B surface antibody (HBs-Ab)
 Hepatitis C virus antibody (HCV-Ab)
x Testing of antibodies to HIV
x Testing for HLA-B27 if unknown at Screening Visit
x CRP testing
x Serum pregnancy testing for women of childbearing potential
x TB evaluation
 Screening chest x-ray must have occurred within 3 months prior to 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).
 TB: IGRA test (QuantiFERON TB GOLD test).
 TB evaluation questionnaire (includes evaluation of signs and symptoms of active TB 
and risk factors for exposure to TB)
x Chest x-ray used for screening must have been done within 3 months prior to the 
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). If no chest x-ray 
is available within the 3 months prior to the Screening Visit, the x-ray can be done during 
the Screening Period.
x For subjects with nr-axSpA, an MRI of the SIJs is to be performed during the Screening 
Period. An MRI performed ≤3 months prior to the Baseline Visit may be used as the 
Baseline. An MRI assessment is not needed for patients with AS.
x AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting 
the mNY classification criteria according to the Investigator. If not available, this x-ray is 
to be taken during the Screening Period. If an x-ray was performed prior to the Screening 
Visit and the mNY classification criteria were met, the x-ray is not to be repeated.
x BASDAI
x Contact the IWRS to indicate the subject has been screened
x Schedule appointment for next visit
The Screening chest x-ray should be read by an experienced TB imaging specialist, 
radiologist, pulmonologist or infectious disease specialist, who is specifically requested to 
look for signs of active TB or signs of past/inactive TB infection and must exclude evidence 
of TB. For subjects with LTBI who initiate a prophylactic treatment and need to have 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 42 of 113
8 weeks of prophylactic treatment prior to randomization, the Screening Period can be 
extended to 12 weeks. For other subjects, the Screening Period should be kept as short as 
possible, but can be up to 5 weeks if certain medications need to be washed out or to allow to 
obtain information from the subjects’ ophthalmologist.
8.2 
Visit 2 (Week 0) Baseline Visit 
Subjects qualifying for the study will have the following procedures performed/recorded 
prior to study medication administration:
x Review of inclusion/exclusion criteria 
x Evaluation of uveitis flares that occurred since last visit
x Prior and concomitant medications
x Vital signs (pulse rate, systolic and diastolic blood pressure, and temperature)
x Physical examination and extra-articular assessment 
 Height
 Weight
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 Number of psoriasis exacerbations (in subjects with concurrent psoriasis)
x Blood samples will be collected for 
 Hematology analyses
 Biochemistry analyses
 CRP testing
x Urine will be collected for 
 Urinalysis 
 Urine pregnancy test for women of childbearing potential
x TB questionnaire
x Patient reported outcomes:
 BASDAI
 BASFI
 ASQoL
 ASAS HI questionnaire
 SF-36
 Total and nocturnal spinal pain
 PtGADA
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 43 of 113
x PhGADA
x Swollen and tender joint counts
x AEs
x Contact IWRS to enroll subject and to obtain kit numbers
x Study drug administration on-site (after all other visit assessments are completed and 
laboratory samples are drawn)
x Schedule appointment for next visit
8.3 
Visit 3 and 4 (Week 2 and 4) 
Assessments at these visits will include:
x Evaluation of uveitis flares that occurred since last visit
x Concomitant medications
x Vital signs (systolic and diastolic blood pressures)
x Physical examination
x Blood samples will be collected for 
 Hematology analyses
 Biochemistry analyses
 CRP testing
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 BASDAI
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 ASQoL
 ASAS HI questionnaire
 SF-36
 Total and nocturnal spinal pain
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 44 of 113
x Study drug administration on-site. At Week 4, syringes of CZP are provided for home 
administration at Weeks 6, 8, and 10. The subject has to return 1 syringe at the Week 12 
Visit. 
x Schedule appointment for next visit
8.4 
Visits 5 and 6, and Visits 8 to 12 (Weeks 12, 24, 36, 48, 60, 72, 
and 84) 
Assessments at these visits will include:
x Evaluation of uveitis flares that occurred since last visit 
x Concomitant medications
x Vital signs (systolic and diastolic blood pressures)
x Physical examination (weight at Week 48 only) and extra-articular assessment (including 
the number of IBD exacerbations and number of psoriasis exacerbations [in subjects with 
concurrent psoriasis])
x Blood samples will be collected for 
 Hematology analyses
 Biochemistry analyses 
 CRP testing 
x Urine will be collected for urinalysis 
x TB test for subjects with previously negative TB test result (Week 48 only)
x TB questionnaire 
x Patient reported outcomes:
 BASDAI 
 BASFI 
 ASQoL 
 ASAS HI questionnaire
 SF-36
 Total and nocturnal spinal pain 
 PtGADA 
x PhGADA
x Swollen and tender joint counts
x AEs
x Contact IWRS to obtain CZP kit numbers
x Study drug administration onsite 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 45 of 113
x Provide subject with CZP for home administration Q2W until next scheduled site visit 
x Schedule appointment for next visit
8.5 
Visit 7 (Week 32) 
Assessments at this visit will include:
x Evaluation of uveitis flares that occurred since last visit
x Concomitant medications
x Vital signs (systolic and diastolic blood pressure)
x CRP testing
x BASDAI
x PtGADA
x AEs
x Contact IWRS to obtain CZP kit numbers
x Study drug administration onsite 
x Provide subjects with CZP for home administration Q2W until next scheduled site visit.
x Schedule appointment for next visit
8.6 
Visit 13 (Week 96/Withdrawal Visit) 
Assessments at this visit will include:
x Evaluation of uveitis flares that occurred since last visit 
x Concomitant medications
x Vital signs (systolic and diastolic blood pressures)
x Physical examination (including weight) and extra-articular assessment (including the 
number of IBD exacerbations and number of psoriasis exacerbations [in subjects with 
concurrent psoriasis])
x Blood samples will be collected for 
 Hematology analyses
 Biochemistry analyses
 CRP testing
x Urine will be collected for 
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 Urine pregnancy test for women of childbearing potential
x TB test for subjects with previously negative TB test result
x TB questionnaire
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 46 of 113
x Patient reported outcomes
 BASDAI
 BASFI
 ASQoL
 ASAS HI questionnaire
 SF-36
 Total and nocturnal spinal pain
 PtGADA
x PhGADA
x Swollen and tender joint counts
x AEs
x Contact IWRS to confirm Week 96/WD Visit
x Schedule appointment for next visit
8.7 
Visit 14 (Follow-Up Visit) 
The FU visit will occur 10 weeks after the final dose. Assessments at this visit will include: 
x Concomitant medications
x Vital signs (systolic and diastolic blood pressures)
x Physical examination
x Urine dipstick pregnancy testing for women of childbearing potential
x AEs
x Contact IWRS to indicate that subject has completed the FU
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 depending on the presenting reason:
x Concomitant medications
x Vital signs
x Blood samples for hematology, biochemistry analyses, other testing such as for TB or 
CRP
x Urine for urinalysis and/or pregnancy testing (for women of childbearing potential)
x Physical examination
x Concomitant medication
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 47 of 113
x AEs
x TB questionnaire 
9 
ASSESSMENT OF EFFICACY 
9.1 
Assessment of primary and secondary efficacy variables 
9.1.1 
Assessment of AU flares 
Subjects will be requested to contact an ophthalmologist when they experience an AU flare at 
any time during the study. The ophthalmologist will confirm the AU flare and determine the 
duration, severity, and treatment. The ophthalmologist will be provided with documentation 
to ensure all protocol-requested information is collected. The documentation will inform the 
ophthalmologist about the subject’s study participation and the requirements.
At each site visit, the subject will be questioned on the occurrence of uveitis flares since last 
visit. In case uveitis flares are confirmed by the subject the site will obtain the needed 
information from the ophthalmologist containing the diagnosis of AU, the affected eye, 
location of the uveitis in the affected eye, duration, severity, and treatment provided.
The following information will be collected:
x Start and end date of each AU flare (episode)
 Start date: when subject experience first signs of the AU episode
 End date: when treatment of the AU is stopped
x Grading
 For uveitis flare, the highest grade noted during an episode of uveitis will be graded 
as follows: 
Grade 0=None; Grade 1+=Faint; Grade 2+=Moderate, iris and lens details clear; 
Grade3+=Marked, iris and lens details hazy; Grade4+=Intense, fibrin or plastic 
aqueous; ND=Not done or not assessed; UNK=Unknown
 For cell count, the highest cell count noted during an episode of uveitis will be graded 
as follows:
Grade 0=<1 cell; Grade 0.5+=1-5 cells; Grade 1+=6-15 cells; Grade 2+=16-25 cells; 
Grade 3+=26-50 cells; Grade 4+=>50 cells; ND=Not done or not assessed; 
UNK=Unknown
x Treatment
9.1.2 
Ankylosing spondylitis disease activity score (ASDAS) 
The ASDAS is comprised of a number of assessments that are scored by the subject and 
physician and multiplied by a proven formula (van der Heijde et al, 2009) as listed:
0.121 × 
 
 (BASDAI Question 2 result; see Section 9.1.3)
0.058 × 
 (BASDAI Question 6 result)
0.110 × PtGADA (see Section 9.1.7)
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 48 of 113
0.073 × 
 (BASDAI Question 3 result)
0.579 × (natural logarithm of the CRP [mg/L] + 1, see Week 32 in Table 5-1)
 PtGADA, 
 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:
x ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥1.3, <2.1
x ASDAS-High Disease activity: ASDAS ≥2.1, ≤3.5
x ASDAS-very High Disease activity: ASDAS >3.5
The variables related to ASDAS improvement are defined as follows:
x ASDAS-CII: ASDAS reduction (improvement) of ≥1.1 relative to Baseline
x ASDAS-Major Improvement: ASDAS reduction (improvement) of ≥2.0 relative to 
Baseline
The ASDAS will be calculated according to the assessment schedule in Table 5-1.
9.1.3 
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, 2015; 
Garrett et al, 1994). The BASDAI is a validated self-reported instrument which consists of 
six 10-unit horizontal NRSs to measure 
 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 visual analog scale (VAS) or 22.5% of the 
Baseline score (Pavy et al, 2005). An MCID of 1 unit will be selected for the NRS version 
(Appendix 16.4).
The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI response.
The BASDAI is calculated as follows:
 item of the BASDAI
 as a major symptom of AS can effectively be measured with single item questions 
such as the BASDAI item (van Tubergen et al, 2002). This item has shown moderate to good 
reliability and responsiveness (van Tubergen et al, 2002). The same MCID will be used for 
the 
 item of the BASDAI and for the total BASDAI score (ie, a change of 1 unit on the 
NRS).
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 49 of 113
The BASDAI assessments per visit are described in the schedule of study assessments
Table 5-1.
9.1.4 
ASAS20, ASAS40, ASAS5/6, and ASAS PR  
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 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]:
x PtGADA (see Section 9.1.7)
x Pain assessment (the average of total and nocturnal spinal pain NRS scores)
x Function (represented by BASFI, Section 9.1.9)
x Inflammation (the mean of the BASDAI questions 5 and 6, [see Section 9.1.3]
)
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 assessments per visit are described in the schedule of study assessments Table 5-1.
9.1.5 
Physician’s global assessment of disease activity (PhGADA) 
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 that are intolerable, and the 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.
9.1.6 
Swollen and tender joint counts (44 joints evaluation) 
The following 44 joints are to be examined for swelling and tenderness by the 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.
x Upper body (4) – bilateral sternoclavicular and acromioclavicular joints.
x Upper extremity (26) – bilateral shoulders, elbows, wrists (includes radiocarpal, carpal, 
and carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I, 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
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II, III, IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, 
and V.
x 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.
9.1.7 
Patient’s global assessment of disease activity (PtGADA) (NRS) 
For the PtGADA questionnaire, 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, 
2015) (Appendix 16.5).
The PtGADA assessments per visit are described in the schedule of study assessments 
Table 5-1.
9.1.8 
Total and nocturnal spinal pain NRS 
The questionnaire for pain in the spine due to AS consists of 2 questions (ie, “How much 
pain of your spine due to spondylitis do you have?”; and “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) (Appendix 16.6).
The pain NRS assessments per visit are described in the schedule of study assessments 
Table 5-1.
9.1.9 
Bath ankylosing spondylitis functional index (BASFI) 
The BASFI is a validated disease-specific instrument for assessing physical function (van 
Tubergen et al, 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, 2002). 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 (Appendix 16.7).
The BASFI assessments per visit are described in the schedule of study assessments 
Table 5-1.
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
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Page 51 of 113
9.1.10 
Extra-articular assessments 
Extra-articular assessments (eg, number of IBD exacerbations and number of psoriasis 
exacerbations [in subjects with concurrent psoriasis]) are to be performed at Screening, 
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, and at Completion at Week 96/WD Visit.
9.2 
Assessment of other efficacy variables 
9.2.1 
Ankylosing spondylitis quality of life (ASQoL) 
The ASQoL, a validated disease specific 18 item questionnaire, has been 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 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 (Appendix 16.8).
9.2.2 
ASAS HI Questionnaire 
The ASAS HI has been developed under the auspices of ASAS to assess health in subjects 
with all forms of SpA. The questionnaire contains 17 items measuring “functioning, 
disability and health” – a concept which is conceptualized in the International Classification 
of Functioning, Disability and Health. The International Classification of Functioning, 
Disability and Health, a model to systematically classify and describe functioning, disability, 
and health in human beings, has been used by ASAS as a basis to define a core set of items 
that are typical and relevant for subjects with AS. Based on this ICF core set for AS, an item 
pool has been developed  containing various items which are linked to specific ICF 
categories including items related to functioning as well as environmental factors. The 
performance of the item pool has been tested and analyzed with Rasch Analysis. The best 
performing items have been included in the final measure. It can be used in clinical studies as 
a new composite index that captures relevant information on the health status of subjects with 
SpA (Klitz et al, 2015) (Appendix 16.9).
Each statement on the ASAS HI is given a score of 1=I agree OR 0=I do not agree. All item 
scores are summed up to give a total score that ranges from 0 (good functioning) to 17 (poor
functioning).
It is to be noted that items 7 and 8 are not applicable for all subjects. For those subjects who 
ticked the response “not applicable,” the sum score is analyzed based on n=16 or n=15, 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
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Missing data:
A total score can be analyzed if no more than 20% of the data are missing. The total score is 
calculated as follows for respondents with 1 to a maximum of 3 missing responses:
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x      X17 x=Item summation score
17-m m=Number of missing items
Cases with more than 3 missing responses cannot be allocated a total score.
The ASAS HI questionnaire assessments per visit are described in Table 5-1.
9.2.3 
Short-Form 36-Item Health Survey (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 Physical Component Summary and Mental Component 
Summary 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 SF-36 Version 2 manual (Ware et al,1994) states the 
following values: physical component summary, 2; mental component summary, 3; physical 
function, 3; role physical, 3; bodily pain, 3; general health, 2; vitality, 2; social functioning, 
3; role emotional, 4; and mental health, 3 (Appendix 16.10).
The SF-36 has been used and has shown to be responsive in axSpA (van Tubergen et al, 
2015; Haibel et al, 2008). The SF-36 will be administered per visit as described in the 
schedule of study assessments Table 5-1.
10 
ASSESSMENT OF SAFETY 
10.1 
Adverse events 
10.1.1 
Definition of adverse event 
An AE is any untoward medical occurrence in a subject 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 
an IMP, whether or not related to the IMP.
To ensure complete safety data collection, all AEs occurring during the study (ie, after the 
signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the eCRF even if no IMP was taken but specific study 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
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procedures were conducted. This includes all AEs not present prior to the initial visit and all 
AEs that recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the IMP is being studied should be 
recorded as AEs only if their nature changes considerably or their frequency or intensity 
increases in a clinically significant manner as compared to the clinical profile known to the 
Investigator from the subject’s history or the Baseline Period.
10.1.2 
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.
10.1.3 
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 CRF 
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 CRF (including judgment of relationship to 
IMP) are described in the CRF Completion Guidelines.
10.1.4 
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 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.
10.1.5 
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:
x 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”
x 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
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22 Jan 2020
Clinical Study Protocol
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AS0007
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Page 54 of 113
10.1.6 
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 Drug Safety (DS) 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:
x The subject should return for an early discontinuation visit.
x The subject should immediately stop the intake of the IMP. 
x A Safety Follow-Up Visit should be scheduled 10 weeks after the subject has 
discontinued her IMP.
The Investigator must inform the subject of information currently known about potential 
risks and about available treatment alternatives.
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 DS department is the primary contact for any questions related to the 
data collection for the pregnancy, eventual birth, and follow-up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, 
the Investigator or designee is asked to contact the subject to request consent of the partner 
via the Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC 
and should be available in the Investigator site file. In case of questions about the consent 
process, the Investigator may contact the UCB/contract research organization (CRO) contract 
monitor for the study. The Investigator will complete the Pregnancy Report and Outcome 
form and send it to UCB’s DS department (for contact details see Serious Adverse Event 
reporting information at the beginning of this protocol) only after the partner has agreed that 
additional information can be captured and has provided the signed Partner Pregnancy 
Consent form. UCB’s DS department is also the primary contact for any questions related to 
the data collection for the partner pregnancy, eventual birth, and follow-up.
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion (elective or spontaneous), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, 
fetal demise, or any congenital anomaly/birth defect of the baby. Those SAEs must be 
additionally reported using the Investigator SAE Report form.
10.1.7 
Overdose of investigational medicinal product 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the Study Drug Dosing module of the CRF. Any SAE or nonserious AE 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 55 of 113
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).
10.1.8 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing 
review of SAEs and perform ongoing SAE reconciliations in collaboration with the DS 
representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory or electrocardiogram [ECG] results) for which data will be periodically 
reviewed during the course of the study.
10.2 
Serious adverse events 
10.2.1 
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:
x Death
x Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred 
in a more severe form.)
x Significant or persistent disability/incapacity
x Congenital anomaly/birth defect (including that occurring in a fetus)
x Important medical event that, based upon appropriate medical judgment, may jeopardize 
the subject 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 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.)
x 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].
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Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or 
manifested in an unusual or uncharacteristic manner] do not qualify for reporting. For 
example, if a subject has a condition recorded on his/her medical history and later has a 
preplanned surgery for this condition, it is not appropriate to record the surgery or 
hospitalization as an SAE, since there is no AE upon which to assess the serious criteria. 
Please note that, if the pre-existing condition has worsened or manifested in an unusual or 
uncharacteristic manner, this would then qualify as an AE and, if necessary, the 
seriousness of the event would need to be determined.)
10.2.2 
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 (FU Visit) for each subject, and to also inform 
participating subjects of the need to inform the Investigator of any SAE within this period. 
Serious AEs that the Investigator thinks may be associated with the 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 IB and 
product information/SPC/Product Monographs, as applicable.
10.2.3 
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 DS 
database without limitation of time.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
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10.3 
Adverse events of interest 
An AE of interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.
Adverse events of interest include:
x Serious infections including opportunistic infections
x Malignancies including lymphoma
x Demyelinating-like disorders
x Congestive heart failure
x Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x Serious bleeding events
x Lupus and lupus-like illness
x Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
x A confirmed LTBI must be reported as an AE of interest
x Confirmed active TB is an AE of interest. In the event that an active TB occurrence 
meets the protocol’s SAE criteria, it is also an SAE.
Note : Potential Hy’s Law, defined as ≥3xULN alanine aminotransferase or aspartate 
aminotransferase with coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline 
phosphatase, with no alternative explanation for the biochemical abnormality, must 
ALWAYS be reported to UCB as an AE of interest (ie, without waiting for any additional 
etiologic investigations to have been concluded). Follow-up information should then be 
reported if an alternative etiology is identified during investigation and monitoring of the 
subject.
10.4 
Immediate reporting of adverse events 
The following AEs must be reported immediately:
x SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality
x Suspected transmission of an infectious agent via a medicinal product
x AE of interest (see Section 10.3)
10.5 
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 10.2.2.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 58 of 113
Table 10‒1: Anticipated serious adverse events in population independent 
of drug exposure 
Population
Anticipated SAE(s) 
Rheumatoid arthritisa
Rheumatoid arthritis
Crohn’s diseasea 
Crohn’s disease 
Perianal abscess
Abdominal pain 
Ankylosing spondylitis 
Ankylosing spondylitis 
Psoriatic arthritis 
Psoriatic arthritis 
JIA 
Juvenile arthritis 
JIA=juvenile idiopathic arthritis; SAE=serious adverse event; RA=rheumatoid arthritis
a The lists of anticipated SAEs were based on the treatment-emergent SAEs with an incidence ≥0.5% in 
subjects who participated in UCB Sponsored placebo-controlled studies who received placebo (Crohn’s 
disease and rheumatoid arthritis safety pooling). 
10.6 
Laboratory measurements 
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline, 
Weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, and 96/WD Visit. Testing for HBs-Ag, HBc-Ab,
HBs-Ab, HCV-Ab, HIV, and HLA-B27 (if not yet known) will be performed at Screening. 
x Hepatitis –associated disease markers
For all subjects, blood samples will be collected by qualified site personnel for the 
determination of the following:
 HBc-Ab
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 HBs-Ab
 HCV-Ab
These samples will be collected at the Screening Visit.
Hepatitis B virus deoxyribonucleic acid and hepatitis C virus ribonucleic acid are available as 
needed to assess the clinical status of subjects if required during the study.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 59 of 113
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 10‒2 lists the laboratory parameters that will be measured:
Table 10‒2: Laboratory measurements 
 
Hematology
Chemistry
Urinalysis
Others
Red blood cells
Sodium 
pH 
Hepatitis B surface 
antigen 
Hemoglobin 
Potassium 
Protein 
Antibodies to 
hepatitis C 
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Chloride 
Glucose  
Antibodies to HIV 
Platelets 
Bicarbonate 
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White blood cells 
Total calcium 
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CRP 
Monocytes 
Glucose 
 
Eosinophils 
Creatinine 
 
Basophils 
Uric acid 
Urea 
Total protein 
Albumin 
 
Alkaline phosphatase 
 
Aspartate 
aminotransferase  
 
Alanine aminotransferase   
Bilirubin 
 
Total cholesterol 
 
CRP= C-reactive protein; HIV= human immunodeficiency virus; HLA-B27= human leukocyte antigen B27; 
RBC=red blood cell; WBC=white blood cell 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 60 of 113
10.6.1 
Pregnancy testing 
Pregnancy testing must be carried out for women of childbearing potential and will consist of 
serum testing at Screening, and urine dipstick testing at Baseline, Week 96/WD Visit, and 
FU Visit.
10.6.2 
Physical assessments 
A physical examination will be performed at Screening, Baseline, Weeks 2, 4, 12, 24, 36, 48, 
60, 72, 84, 96/WD Visit, and at the FU Visit. 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:
x General Appearance
x Ear, Nose, and Throat
x Eyes
x Hair and Skin
x Respiratory
x Cardiovascular
x Gastrointestinal
x Musculoskeletal
x Hepatic
x Neurological (including limb reflexes)
x Mental status
In addition, the TB signs and symptoms questionnaire will be performed at Screening, 
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96/WD Visit.
Weight will be measured at Screening, Baseline, Week 48, and at Completion at Week 
96/WD Visit. Height will be measured at the Baseline Visit only. 
10.6.3 
MRI assessments 
Magnetic resonance imaging of the SIJs will be performed at the Screening Visit only. An
MRI performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
10.6.4 
Tuberculosis assessments 
10.6.4.1 
Tuberculosis test 
The IGRA test that will be used by the central laboratory is the QuantiFERON®-TB Gold 
In-Tube (QFT-GIT) test or updated version (QuantiFERON® Plus). The test results will be 
reported as positive, negative, or indeterminate and must be reviewed by an experienced TB 
specialist, radiologist, or a pulmonologist.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 61 of 113
The TB test will be performed at the following timepoints:
x At Screening, all subjects will have a QuantiFERON-TB GOLD In-Tube test. 
x At Week 48 and 96/WD Visit all subjects with a negative Quantiferon-TB GOLD 
In-Tube test at Screening will have the test repeated. 
For subjects with a positive Quantiferon-TB GOLD In-Tube test at Screening, the test is not 
to be repeated at Weeks 48 and 96/WD Visit. 
x Per the judgment of the Investigator, a QuantiFERON-TB GOLD In-Tube test can be 
performed at unscheduled visits at any time during the study.
In case of an indeterminate result, a retest must be done shortly after, during the 
protocol-defined Screening window. If the test is positive or indeterminate on retest, the 
subject may not be randomized to IMP without further evaluation by a TB specialist. If 
LTBI is identified, appropriate treatment for TB prophylaxis and discussion with the 
study physician is required. If active TB is identified the subject cannot be randomized 
and is excluded from the study.
x At any other timepoint during the study if the IGRA test result is indeterminate, the 
IGRA must be reported once shortly after.
If during the study the assessment by IGRA is positive or indeterminate on retest for subjects 
who were previously negative at Screening and not treated for LTBI, the subject may not 
continue study treatment without further evaluation by a TB specialist and discussion with 
the Medical Monitor. If LTBI is identified, study treatment can only be re-initiated after 
prophylactic TB treatment is initiated. If active TB is identified, the subject must undergo 
appropriate study-specified withdrawal procedures.
Conditions for including LTBI subjects in the study:
x The Investigator must provide full documentation of the duration, and start and stop dates 
of LTBI treatments, and discuss with the study physician prior to allowing subject to 
screen (if the LTBI was discovered prior to subject screening) or prior to receiving study 
drug (if LTBI was identified at screening).
x Subjects who initiate treatment for LTBI during the Screening Period must repeat initial 
screening laboratory parameters, examination, and questionnaires (after receiving at least 
4 weeks duration of treatment for LTBI) prior to randomization in the study, and must 
plan to continue the full course of LTBI prophylaxis therapy. The Investigator must 
assess that the subject’s likelihood of completing the therapy is high and duly record 
his/her opinion in the subject’s record prior to randomizing the subject. It is suggested to 
obtain the opinion of a TB specialist, especially for subjects having been in contact with 
multi-resistant TB.
x An extension of the Screening Period up to 12 weeks is allowed in order to allow for 
8 weeks of LTBI treatment prior to study drug initiation. If the initial 8 weeks of 
prophylactic LTBI therapy cannot be accomplished with the extended Screening Period, 
the subject should be considered screen failed.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 62 of 113
x Rescreening may occur only after discussion with and approval by the study physician 
(or Medical Monitor)
Procedure to be followed for subjects with conversion of IGRA or diagnosis of a new TB 
infection during the Study:
x Conversion is defined as a positive IGRA or 2 indeterminate results at the same visit 
(scheduled or unscheduled) of the same IGRA method.
x The subject should immediately discontinue study drug intake upon positive test
conversion. Should evaluation of the subject by the appropriate TB specialist result in a 
diagnosis of LTBI, the study drug must be withheld until the appropriate prophylactic 
therapy has been received for at least 4 weeks and the subject is deemed likely to 
continue therapy to completion. The treatment must be discussed with the study 
physician before study drug is restarted.
x If the subject’s evaluation reveals active TB infection during the course of 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 FU Visit as specified by the protocol.
x Refer to Section 10.4, for instructions on reporting a confirmed LTBI or confirmed active 
TB occurrence (note that in the event that an active TB occurrence meets the 
protocol-defined SAE criteria, it is also an SAE).
10.6.4.2 
Chest x-ray 
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).
Imaging must be read by an experienced TB imaging specialist, radiologist, pulmonologist or 
infectious disease specialist, who is specifically requested 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.
Additional chest x-ray or other imaging test should be performed when positive signs and 
symptoms indicate pulmonary infection, including potential TB infection, or when close 
exposure to persons with TB is documented.
10.6.4.3 
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 completion at Week 96/WD Visit. 
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 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 63 of 113
has latent or active TB (see Exclusion Criterion 24, Section 6.2). A “Yes” response to any of 
the questions during the study should trigger further assessments to determine whether the 
subject has either LTBI or active TB infection (Appendix 16.11).
Subjects with a LTBI must receive prophylactic therapy prior to continuing study 
medication.
Subjects with active TB infection must be withdrawn from the study and should be referred 
to a TB specialist for further assessments.
11 
STUDY MANAGEMENT AND ADMINISTRATION  
11.1 
Adherence to protocol 
The Investigator should not deviate from the protocol. However, the Investigator should take 
any measure necessary in deviation from or not defined by the protocol 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 a measure, the Investigator must notify the Clinical Project 
Manager of the Sponsor within 24 hours and follow any local regulatory requirements.
11.2 
Monitoring 
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring Standard 
Operating Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, 
and to ensure that study initiation, conduct, and closure are adequate. Monitoring of the study 
may be delegated by UCB to a CRO or a contract monitor.
The Investigator and his/her staff will be 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 CRFs 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 CRFs, ensure that 
all protocol requirements, applicable authorities regulations, and Investigator’s obligations 
are being fulfilled, and resolve any inconsistencies in the study records.
11.2.1 
Definition of source data  
All source documents must be accurate, clear, unambiguous, permanent, and capable of 
being audited. They should be made using some permanent form of recording (ink, typing, 
printing, optical disc). They should not be obscured by correction fluid or have temporary 
attachments (such as removable self-stick notes). Photocopies of CRFs 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, 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 64 of 113
printouts, pharmacy records, care records, ECG or other printouts, completed scales, or 
quality of life questionnaires, for example. Source documents should be kept in a secure, 
limited access area.
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor. 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 must be saved and stored as instructed by UCB (or its designee).
The following data will be recorded directly in the electronic patient reported outcome 
(ePRO) device (Section 11.3.2) on site and will not appear in a source document as defined 
above:
x Patient PROs: BASDAI, BASFI, ASQoL, ASAS HI questionnaire, SF-36, total and 
nocturnal spinal pain, and PtGADA,
x PhGADA and swollen and tender joint counts
11.2.2 
Source data verification 
Source data verification ensures accuracy and credibility of the data obtained. During 
monitoring visits, reported data should be 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 CRF 
should be supported by source documents, unless otherwise specified in Section 11.2.1.
11.3 
Data handling 
11.3.1 
Case Report Form completion 
This study will use remote data capture (RDC); and 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 the ePRO questionnaires 
(see Section 11.3.2).
Serious adverse event reporting will be done using the SAE form (Section 10.2) 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.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 65 of 113
11.3.2 
Electronic reporting outcome 
Compared to the paper patient 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 time for monitoring of subject symptoms and compliance. The 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. 
Access to the system by site personnel 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 electronic ePRO device.
11.3.3 
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. Case Report Form data are entered into the clinical database using 
independent, double-data entry, with the exception of comment fields, which are verified by 
a second person. In the event that the 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.
11.3.4 
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.
11.4 
Termination of the study 
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at 
a single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform 
the Investigators/institutions and the regulatory authority(ies) of the termination or 
suspension and the reason(s) for the termination or suspension, in accordance with applicable 
regulatory requirement(s). The IRB/IEC should also be informed and provided with reason(s) 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 66 of 113
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:
x Return of all study data to the Sponsor or its representative
x Data clarification and/or resolution
x Accountability, reconciliation, and arrangements for used and unused study drugs
x Review of site study records for completeness
x Discussion/reminder on archiving responsibilities
11.5 
Archiving and data retention 
The Investigator will maintain adequate records for the study, including CRFs, medical 
records, laboratory results, Informed Consent documents, drug dispensing and disposition 
records, safety reports, information regarding participants who discontinued, and other 
pertinent data.
All essential documents should 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.
11.6 
Audit and inspection 
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, 
and inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of 
the subjects enrolled have been protected, that enrolled subjects (ie, signing consent and 
undergoing 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).
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 67 of 113
11.7 
Good Clinical Practice 
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt 
action by UCB to secure compliance. Continued noncompliance may result in the 
termination of the site’s involvement in the study.
12 
STATISTICS 
A summary of statistical methods follows; more details will be provided in the Statistical 
Analysis Plan (SAP).
12.1 
Definition of analysis sets 
Two analysis sets are defined for this study:
x The Enrolled Set (ES) will consist of all subjects who have given informed consent.
x The Safety Set (SS) will consist of all subjects in the ES who have received at least 
1 dose of study medication.
Efficacy variables will be analyzed using the SS. In the unexpected case that subjects in the 
SS have an unknown incidence of AU flares for the prestudy period (ie, missing Baseline 
value for the primary efficacy variable), then a Full Analysis Set (FAS) would additionally 
be defined for efficacy analysis as all subjects in the SS with nonmissing Baseline value for 
the primary efficacy variable (ie, AU flare incidence data from prestudy period). In this 
situation, efficacy analysis would be conducted using the FAS rather than the SS.
Safety variables will be summarized using the SS.
12.2 
General statistical considerations 
In general, summary statistics (n [number of available measurements], arithmetic mean, SD, 
median, minimum, and maximum) for quantitative variable and frequency tables for 
qualitative data will be presented. As there is a single treatment arm in this study, all subjects
will be presented together in a single treatment group (eg, as “All CZP” or similar).
Unless otherwise specified, the last valid measurement before study medication 
administration will be utilized as Baseline value.
All statistical analyses besides the primary efficacy analysis will be exploratory in nature 
only. Any p-values or confidence intervals produced in association with secondary or other 
analyses will be considered non-confirmatory.
The full details of the statistical analyses will be provided in the SAP. Any deviations from 
the final SAP as well as changes from the protocol will be detailed in the SAP and discussed 
in the Clinical Study Report.
All the analyses will be performed by using SAS Version 9.4 or above. The details regarding 
the presentation of statistical outputs will be provided in the SAP.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 68 of 113
12.3 
Planned efficacy analyses 
12.3.1 
Analysis of the primary efficacy variable 
The primary efficacy analysis will consist of a comparison of the frequency of AU flares 
during the prestudy/historical period with that observed while in the study during CZP 
treatment. It is assumed that the frequency of AU flares follows a Poisson distribution. As 
such, the analysis will be performed as a generalized estimating equations analysis for 
Poisson outcome that will take into account the possible within-subject correlation (between 
the retrospective and prospective AU flare counts). The model will contain 2 records per 
subject corresponding to the frequency of AU flares before study and during the study, offset 
by log-time of each of the reporting periods. Disease duration will be included as a factor in 
the model, initially defined as <2 years and ≥2 years; the specific cutoffs for analysis may 
deviate from this based on the distribution seen in the data. The p-value for effect of CZP 
treatment on frequency of AU flares, along with rate ratio (CZP/historical) and 95% 
confidence interval, will be obtained from this model. 
The above analysis will be repeated in the subgroup of subjects with at least 1 documented 
AU flare within 12 months prior to Baseline.
The primary efficacy analysis hypothesis will be tested based on significance level of 
alpha 0.05 and will be 2 sided. The entire alpha will be used for the primary efficacy analysis 
and analysis of the other secondary efficacy parameters will be supportive. Therefore, no 
alpha adjustment will be performed.
12.3.2 
Other efficacy analyses 
The AU flare rate (event rate) per 100 patient-years of exposure, both before and during the 
study, along with 95% confidence intervals (Garwood, 1936) will be presented as a key 
supportive analysis to the primary efficacy analysis results.
Other efficacy variables will be summarized by time point including change from Baseline or 
shift from Baseline, with descriptive statistics.
12.4 
Planned safety analyses 
12.4.1 
Safety analyses 
The frequency of all AEs will be presented 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.
Laboratory evaluations and vital signs will be analyzed over time in the SS for observed 
cases and at the end of treatment. The details will be elaborated in the SAP.
12.5 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which could potentially have a 
meaningful impact on study conduct, on the safety for an individual subject, or on the 
primary efficacy outcome for an individual subject. The criteria for identifying important 
protocol deviations will be defined within the appropriate document. All the important 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 69 of 113
protocol violations will be tracked, although no analysis will be performed based on per 
protocol population.
12.6 
Handling of dropouts or missing data 
Analysis based on observed case and last observation carried forward for continuous 
variables or nonresponder imputation for categorical variables will be presented.
12.7 
Planned interim analysis and data monitoring 
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. 
An interim analysis is scheduled after the last subject has completed the Week 48 
assessment. Details of the interim analysis will be included within the final SAP (or an 
interim SAP, if a separate SAP is needed specific to details of the interim analysis).
Although there is no intention to stop the study early due to efficacy or futility on the basis of 
these interim results, α=0.0001 will be spent in conjunction with this formal interim review 
of the data (Haybittle, 1971), and the final analysis of the primary efficacy variable will be 
conducted at the reduced 2-sided α-level of 0.049.
12.8 
Determination of sample size 
Based on results from a previous study with CZP in axSpA subjects (AS001), the AU flare 
rate while treated with CZP is estimated to be 14.6 events per 100 subject-years of exposure. 
Assuming the rate while treated with CZP represents a reduction in the flare rate of 
approximately 50%, the AU flare rate for the prestudy period prior to initiation of CZP is 
estimated to be 29.2 events per 100 subject-years of exposure. A conservative estimate of the 
sample size for this study is obtained via derivation of the per treatment-group sample size 
for Poisson regression based on the approach for a 2-group setting initially described by 
Signorini (1991) and implemented within SAS (Hu, 2008). Assuming an average follow-up
period of 1.5 years with 2-sided α-level=0.049 for the final analysis of the primary efficacy 
variable, a sample size of N=86 subjects per treatment group will have 80% statistical power 
for a 2 group comparison, corresponding to a total sample size of N=86 subjects for this 
study with 1 treatment group. Due to the expected increase in statistical efficiency from the 
fact that each subject serves as his/her own control in the primary efficacy analysis, the actual 
power for this study is assumed to be >80 percent.
13 
ETHICS AND REGULATORY REQUIREMENTS 
13.1 
Informed consent 
Subject’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki.
Prior to obtaining informed consent, information should be given in a language and at a level 
of complexity understandable to the subject in both oral and written form by the Investigator 
(or designee). Each subject will have the opportunity to discuss the study and its alternatives 
with the Investigator prior to participation in the study.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 70 of 113
Prior to participation in the study, the written ICF 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 ICF. As part of the consent process, each subject must 
consent to give direct access to his/her medical records for study-related monitoring, 
auditing, IRB/IEC review, and regulatory inspection.
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF 
by the IRB/IEC and use of the amended form.
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 ICF. A CRF must not be 
started, nor may any study specific procedure be performed for a given subject, without 
having obtained his/her written consent to participate in the study.
13.2 
Subject identification cards 
Upon signing the ICF, the subject or his/her 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.
13.3 
Institutional Review Boards and Independent Ethics 
Committees 
The study will be conducted under the auspices of an IRB/IEC, as defined in local 
regulations, ICH-GCP, and in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies 
with the requirements of the current ICH-GCP version or applicable country-specific 
regulations will be responsible for the initial and continuing review and approval of the 
clinical study. Prior to initiation of the study, the Investigator/UCB will forward copies of the 
protocol, Informed Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if 
applicable), advertisement (if applicable), and all other subject-related documents to be used 
for the study to the IRB/IEC for its review and approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. Approval from the authorities should also be obtained 
before study initiation.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol 
deviations, to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. 
For minor changes to a previously approved protocol during the period covered by the 
original approval, it may be possible for the Investigator to obtain an expedited review by the 
IRB/IEC as allowed.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 71 of 113
As part of the IRB/IEC requirements for continuing review of approved studies, the 
Investigator will be responsible for submitting periodic progress reports to the IRB/IEC
(based on IRB/IEC requirements), at intervals appropriate to the degree of subject risk 
involved, but no less than once per year. The Investigator should provide a final report to the 
IRB/IEC following study completion.
UCB (or its representative) will communicate safety information to the appropriate 
regulatory authorities and all active Investigators in accordance with applicable regulatory 
requirements. The appropriate IRB/IEC will also be informed by the Investigator or the 
Sponsor, as specified by the applicable regulatory requirements in each concerned country. 
Where applicable, Investigators are to provide the Sponsor (or its representative) with 
evidence of such IRB/IEC notification.
13.4 
Subject privacy 
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject number 
assigned at Screening.
The Investigator agrees that representatives of UCB, its designee, representatives of the 
relevant IRB/IEC, or representatives of regulatory authorities will be allowed to review that 
portion of the subject’s primary medical records that directly concerns this study (including, 
but not limited to, laboratory test result reports, ECG reports, admission/discharge summaries 
for hospital admissions occurring during a subject’s study participation, and autopsy reports 
for deaths occurring during the study).
13.5 
Protocol amendments 
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and 
must be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to 
being implemented.
14 
FINANCE, INSURANCE, AND PUBLICATION 
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights will be addressed in the Investigator and/or CRO 
agreements, as applicable.
15 
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 72 of 113
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22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 73 of 113
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adalimumab in the treatment of axial spondylarthritis without radiographically defined 
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 74 of 113
Klitz U, van der Heijde D, Boonen A, Cieza A, Stucki G, Khan MA, et al. Development of a 
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16 
APPENDICES 
16.1 
Modified NY criteria for ankylosing spondylitis 
Subjects meeting the NY criteria in the context of this protocol are defined as subjects 
meeting the definite AS diagnosis according to the modified NY criteria below. 
Modified NY criteria for ankylosing spondylitis 
Diagnosis
1) Clinical criteria
a) Low back pain and stiffness for more than 3 months which improves with exercise, but is not 
relieved by rest.
b) Limitation of motion of the lumbar spine in both the sagittal and frontal planes.
c) Limitation of chest expansion relative to normal values corrected for age and sex.
2) Radiologic criterion
Sacroiliitis grade ≥2 bilaterally or sacroiliitis grade 3 to 4 unilaterally.
Grading
1) Definite ankylosing spondylitis if the radiologic criterion is associated with at least 1 clinical 
criterion
Note: A second grading of “probably ankylosing spondylitis” is part of the modified NY criteria, but it is 
not applicable for this study. It is included here for completeness. The grading will be probable ankylosing 
spondylitis if three clinical criteria are present and the radiologic criterion is present without any signs or 
symptoms satisfying the clinical criteria (other causes of sacroiliitis should be considered).
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Page 78 of 113
16.2 
ASAS classification criteria for axSpA 
ASAS classification criteria for axSpA
(for subjects with chronic back pain ≥3 months and age at onset <45 years)
Imaging criteria
ASAS clinical criteria for axSpA
Sacroiliitis (MRI or radiographsa) plus ≥1 SpA 
feature
HLA-B27 plus ≥2 other SpA features
SpA featuresb
Inflammatory back painc
Arthritis 
Enthesitis (heel) 
Uveitis 
Dactylitis
Psoriasis
Crohn’s disease/ulcerative colitis
Good response to NSAIDs
Family history for SpA
HLA-B27
Elevated CRP
ASAS=Assessment of SpondyloArthritis international Society; axSpA=axial spondyloarthritis; 
CRP=C-reactive protein; MRI=magnetic resonance imaging; HLA-B27=human leukocyte antigen 
B27; NSAID=nonsteroidal anti-inflammatory drug; SpA=spondyloarthritis
a Active 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 <40 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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Page 79 of 113
16.3 
Corticosteroid equivalent doses 
Table 16‒1: Corticosteroid equivalent doses (with reference to prednisone 
10mg dose) (Meikle and Tyler, 1977) 
Prednisone (reference)
10mg
Cortisone
50mg
Hydrocortisone
40mg
Prednisolone
10mg
Triamcinolone
8mg
Methylprednisolone
8mg
Betamethasone
1.5mg
Dexamethasone
1.5mg
 
 
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16.5 
PtGADA (NRS) 
NRS patient global disease activity 
How active was your spondyloarthritis on average during the last week? 
Please tick the box that represents your answer ( ie,     10          ) 
Not active
very active
 
 
0
1
2
3
4
5
6
7
8
9
10
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Page 82 of 113
16.6 
Total spinal pain NRS and nocturnal spinal pain NRS 
NRS pain
p
Please tick the box that represents your answer ( i.e. 
)
1. Total SpinePain
p
How much pain of your spine due to spondyloarthritis do you have?
o
no pain
most severe pain
2. Nocturnal SpinePain
p
How much pain of your spine due to spondyloarthritis do you have at night?
no pain
most severe pain
10
1
2
3
4
6
7
8
9
10
5
0
1
2
3
4
6
7
8
9
10
5
0
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16.9 
ASAS Health Index Questionnaire 
 
ASAS Health Index 
Name:            
Date:                             
 
 
Please answer all statements by placing one check mark per statement to indicate 
which response best applies to you at this moment in time taking into account your 
rheumatic disease (the term “rheumatic disease” contains all forms of spondyloarthritis 
including ankylosing spondylitis) . 
 
1. 
Pain sometimes disrupts my normal activities. 
□ I agree 
□ I do not agree 
2. 
I find it hard to stand for long. 
□ I agree 
□ I do not agree 
3. 
I have problems running. 
□ I agree 
□ I do not agree 
4. 
I have problems using toilet facilities. 
□ I agree 
□ I do not agree 
5. 
I am often exhausted. 
□ I agree 
□ I do not agree 
 
6. 
I am less motivated to do anything that requires physical effort. 
□ I agree 
□ I do not agree 
 
7. 
I have lost interest in sex. 
□ I agree 
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Page 88 of 113
□ I do not agree 
□ Not applicable, I do not want to answer 
 
8. 
I have difficulty operating the pedals in my car. 
□ I agree 
□ I do not agree 
□ Not applicable, I cannot / do not drive 
9. 
I am finding it hard to make contact with people. 
□ I agree 
□ I do not agree 
10. I am not able to walk outdoors on flat ground. 
□ I agree 
□ I do not agree 
11. I find it hard to 
concentrate. 
□ I agree 
□ I do not agree 
12. I am restricted in traveling because of my mobility. 
□ I agree 
□ I do not agree 
13. I often get frustrated. 
□ I agree 
□ I do not agree 
14. I find it difficult to wash my hair. 
□ I agree 
□ I do not agree 
15. I have experienced financial changes because of my rheumatic disease. 
□ I agree 
□ I do not agree 
16. I sleep badly at night. 
□ I agree 
□ I do not agree 
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Page 89 of 113
 
 
ASAS Health 
Index 
 
 
17. I cannot overcome my 
difficulties. 
□ I agree 
□ I do not agree. 
 
Thank you for answering this questionnaire 
 
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Environmental factors related
to ASAS Health Index 
Date:  
 
Name:  
 
Please answer all statements by placing one check mark per statement to indicate which response 
best applies to you at this moment in time taking into account your rheumatic disease (the term 
“rheumatic disease” contains all forms of spondyloarthritis including ankylosing spondylitis). 
As a result of my rheumatic disease, my family / relatives take more responsibility for household tasks. 
□I agree 
□I do not agree 
I don’t like the way my friends act around me. 
□I agree 
□I do not agree 
I cannot count on my relatives to help me with my problems. 
□I agree 
□I do not agree 
I modify my home and work environments. 
□I agree 
□I do not agree 
I have difficulties getting worsening of my disease acknowledged by a health care professional. 
□I agree 
□I do not agree 
Treatment of my rheumatic disease is taking up time. 
□I agree 
□I do not agree 
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Page 91 of 113
My friends expect too much of me. 
□I agree 
□I do not agree 
No one pays much attention to me at home. 
□I agree 
□I do not agree 
My friends understand me. 
□I agree 
□I do not agree 
Thank you for answering this questionnaire 
 
 
Developed by Assessment of SpondyloArthritis International Society (ASAS)  
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17 
APPENDICES 
17.1 
Protocol Amendment 1 
Rationale for the amendment
The purpose of this non-substantial amendment is to clarify the Screening requirement for MRI 
and history of tobacco use, and to incorporate the administration of IMP at Week 32.  
 
Modifications and changes 
Global changes
Magnetic resonance imaging of the spine at Screening is not required for this study. An MRI of 
the SIJs will be performed during the Screening Period, or an MRI of the SIJs performed 
≤3 months prior to the Baseline Visit may be used as the Baseline.
The IMP will be administered onsite at Visit 7 (Week 32).
Specific changes 
Change #1
Table 5-1: Schedule of assessments
Row 4
Medical history (including axSpA history) and concomitant diseases 
Has been changed to:
Medical history (including axSpA history, and tobacco use) and concomitant diseases 
Change #2 
Table 5-1: Schedule of assessments
Row 29
“Study drug sc injections” has been checked for Visit 7 (Week 32).
Change #3 
Table 5-1: Schedule of assessments
Footnote k
Magnetic resonance imaging of the spine and SIJs to be performed during the Screening Period. 
An MRI performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
Has been changed to: 
Magnetic resonance imaging of the SIJs to be performed during the Screening Period. An MRI 
performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
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Change #4 
Section 8.1 Visit 1 (Week -5 to -1) Screening 
Bullet point 5
x Significant past medical and procedure history and concomitant disease (including axSpA 
history) 
Has been changed to: 
x Significant past medical and procedure history (including tobacco use) and concomitant 
disease (including axSpA history) 
Change #5 
Section 8.1 Visit 1 (Week -5 to -1) Screening 
Bullet point 17
x MRI evaluation of the spine and SIJ. An MRI performed ≤3 months prior to the Baseline 
Visit may be used for assessing the eligibility at Baseline.
Has been changed to: 
x MRI evaluation of the SIJ. An MRI performed ≤3 months prior to the Baseline Visit may be 
used for assessing the eligibility at Baseline.
Change #6 
Section 8.5 Visit 7 (Week 32) 
Bullet point 9 has been added:
x Study drug administration onsite 
Change #7 
Section 10.6.3 MRI assessments
Magnetic resonance imaging of the spine and SIJs will be performed at the Screening Visit only. 
An MRI performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
Has been changed to: 
Magnetic resonance imaging of the SIJs will be performed at the Screening Visit only. An MRI 
performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
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Page 101 of 113
17.2 
Protocol Amendment 2 
Rationale for the amendment
The main purpose of this substantial amendment is to provide clarification on magnetic 
resonance imaging (MRI) and x-ray assessments. In addition, text was added to the protocol 
about information collected for the assessment of AU flares and about Hy’s Law cases, and other 
minor updates/clarifications were also done to the protocol (see global changes below). Details 
of each specific change are provided below.
Modifications and changes 
Global changes 
x Clarification has been added that if no chest x-ray is available within the 3 months prior to 
Screening, the x-ray can be done during the Screening Period. If the modified New York 
(mNY) classification criteria were met in the x-ray performed prior to Screening, the x-ray is 
not to be repeated.
x Clarification has been added that an MRI assessment is not needed for subjects with AS and 
that AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting 
the mNY classification criteria according to the Investigator.
x Minor updates have been made to ophthalmic exclusion criteria and prior concomitant 
medications exclusion table.
x Minor edits have been made to text about storage conditions at the site.
x Details about the information collected for the assessment of AU flares have been added to 
the protocol.
x Text about Hy’s Law cases has been added to the Adverse Events of Interest section.
x Minor corrections have been done to the table in Appendix 16.2.
x Minor editorial and format corrections have been done to the protocol.
Specific changes 
Change #1
Table 5-1: Schedule of assessments
Row 17
MRIk
Has been changed to:
MRI (nr-axSpA subjects only)k
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 102 of 113
Change #2 
Table 5-1: Schedule of assessments
Row 18 has been added and checked for Period 1 Screening Visit:
X-ray (AS subjects only)l
Change #3 
Table 5-1: Schedule of assessments, footnote i
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).
Has been changed to: 
i Chest x-ray used for screening must have been done within 3 months prior to the 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). If no chest x-ray is available within the 
3 months prior to the Screening Visit, the x-ray can be done during the Screening Period.
Change #4 
Table 5-1: Schedule of assessments, footnote k
k Magnetic resonance imaging of the SIJs to be performed during the Screening Period. An MRI 
performed ≤3 months prior to the Baseline Visit may be used as the Baseline.
Has been changed to: 
k For subjects with nr-axSpA, an MRI of the SIJs is to be performed during the Screening 
Period. An MRI performed ≤3 months prior to the Baseline Visit may be used as the Baseline. 
An MRI assessment is not needed for patients with AS.
Change #5 
Table 5-1: Schedule of assessments, new footnote l
Footnote l has been added (for new Row 18 and former footnote l has been renumbered to 
footnote m):
l AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting the 
mNY classification criteria according to the Investigator. If not available, this x-ray is to be 
taken during the Screening Period. If an x-ray was performed prior to the Screening Visit and 
the mNY classification criteria were met, the x-ray is not to be repeated.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 103 of 113
Change #6 
Section 6.1 Inclusion Criteria 
Inclusion criterion 6, bullets 3 and 4
 Nr-axSpA subjects must either have CRP > upper limit of normal (ULN) and/or current 
evidence of sacroiliitis on MRI taken within 3 months prior to Baseline (no confirmation 
by central reading) as defined by ASAS criteria
 AS subjects must have evidence of sacroiliitis on x-ray taken within 12 months prior to 
Baseline meeting mNY criteria according to the Investigator
Have been changed to: 
 Nr-axSpA subjects must either have CRP > upper limit of normal (ULN) and/or current 
evidence of sacroiliitis on MRI (no confirmation by central reading) as defined by ASAS 
criteria
 AS subjects must have evidence of sacroiliitis on x-ray meeting the mNY classification 
criteria according to the Investigator
Change #7 
Section 6.2 Exclusion Criteria 
Ophthalmic exclusion criteria
Exclusion criterion 9
10.9.Any condition or complicating factor that may interfere with the AU assessment, for 
example:
a. Intraocular pressure of ≥25 mmHg
b. Corneal or lens opacity
c. Proliferative or severe nonproliferative diabetic retinopathy or clinically significant 
macular edema due to diabetic retinopathy
d. Neovascular/wet age-related macular degeneration
e. History of scleritis
Has been changed to: 
11. 9.Any condition or complicating factor that may interfere with the AU assessment, for 
example:
a. History of cataract surgery within 6 months prior to Baseline
b. Corneal or lens opacity
c. Proliferative or severe nonproliferative diabetic retinopathy or clinically significant 
macular edema due to diabetic retinopathy
d. Neovascular/wet age-related macular degeneration
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 104 of 113
e. History of scleritis
f. History of intraocular surgery, with the exception of phacoemulsification
Change #8 
Exclusion criterion 16
Table 6-1: Concomitant Medications (Prior to Baseline and Study Visits)
Rows 8, 9, and 10:
Table 6-1: Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
DMARDs:
hydroxychloroquine (HCQ) 
and/or methotrexate (MTX)
Maximum allowed:
HCQ ≤400mg daily 
MTX ≤25mg weekly
Use initiated in and/or any change 
in the dose regimen in the 28 days 
prior to the Baseline Visit is 
exclusionary.
DMARDs dose should be kept 
stable throughout the study except 
for reasons of intolerance, where 
the DMARD dose may be 
decreased but not discontinued.
DMARDs:
sulfasalazine (SSZ), azathioprine, 
cyclosporine, cyclophosphamide, 
mycophenolic acid, apremilast
Any dose
Use within 28 days prior to the 
Baseline Visit is exclusionary.
Must not be started during the 
study.
DMARDs:
leflunomide
Any dose
Use in the 6 months prior to the 
Baseline Visit is exclusionary 
unless a cholestyramine washout 
has been performed. In case of a 
cholestryramine washout, use 
28 days prior to the Baseline Visit 
is acceptable. 
Must not be started during the 
study.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 105 of 113
Have been changed to: 
Table 6-1: Concomitant Medications (Prior to Baseline and Study Visits)
Drug class
Dose
Exclusion criteria
Disease-modifying antirheumatic 
drugs (DMARDs):
sulfasalazine (SSZ) and/or 
hydroxychloroquine (HCQ) 
and/or methotrexate (MTX) 
and/or leflunomide (LFN) and/or 
azathioprine (AZA)
Maximum allowed:
SSZ ≤3g daily
HCQ ≤400mg daily
MTX ≤25mg weekly
AZA ≤150mg daily
LFN ≤20mg daily
Use initiated in and/or any change 
in the dose regimen in the 28 days 
prior to the Baseline Visit is 
exclusionary.
DMARDs dose should be kept 
stable throughout the study except 
for reasons of intolerance, where 
the DMARD dose may be 
decreased.
DMARDs:
cyclosporine, cyclophosphamide, 
mycophenolic acid, apremilast
Any dose
Use within 28 days prior to the 
Baseline Visit is exclusionary.
Must not be started during the 
study.
Change #9 
Section 7.5.1 Storage at the site
Paragraph 3
Appropriate storage conditions must be ensured by both controlled room temperature and 
completion of a temperature log in accordance with local requirements on a regular basis 
(eg, once a week), but at least once per working day showing minimum and maximum 
temperatures reached over the time interval. In case of an out of range temperature, based on 
discussion with a UCB Quality Assurance representative, the Drug Supply Coordinator will then 
provide the site with instructions regarding use of the IMP and adjust the status of the IMP as 
needed in the IWRS.
Has been changed to: 
Appropriate storage conditions (storage of CZP is to be done at 2 to 8ºC) must be ensured and 
completion of a temperature log in accordance with local requirements must be done on a regular 
basis (eg, once a week), but at least once per working day showing minimum and maximum 
temperatures reached over the time interval. In case of an out of range temperature, based on 
discussion with a UCB Quality Assurance representative, the Drug Supply Coordinator will then 
provide the site with instructions regarding use of the IMP and adjust the status of the IMP as 
needed in the IWRS.
Change #10 
Section 8.1 Visit 1 (Week -5 to -1) Screening
Bullet 17
x MRI evaluation of the SIJ. An MRI performed ≤3 months prior to the Baseline Visit may be 
used for assessing the eligibility at Baseline.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 106 of 113
Has been changed to: 
x For subjects with nr-axSpA, an MRI of the SIJs is to be performed during the Screening 
Period. An MRI performed ≤3 months prior to the Baseline Visit may be used as the 
Baseline. An MRI assessment is not needed for patients with AS.
And the following bullets have been added above and below Bullet 17: 
x Chest x-ray used for screening must have been done within 3 months prior to the 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). If no chest x-ray is available 
within the 3 months prior to the Screening Visit, the x-ray can be done during the Screening 
Period.
x AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting the 
mNY classification criteria according to the Investigator. If not available, this x-ray is to be 
taken during the Screening Period. If an x-ray was performed prior to the Screening Visit and 
the mNY classification criteria were met, the x-ray is not to be repeated.
Change #11 
Section 9.1.1 Assessment of AU flares
Subjects will be requested to contact their ophthalmologist when they experience an AU flare at 
any time during the study. The ophthalmologist will confirm the AU flare and determine the 
duration, severity, and treatment. The subject’s ophthalmologist will be provided with 
documentation to ensure all protocol-requested information is collected. The documentation will 
inform the subject’s ophthalmologist about the subject’s study participation and the 
requirements.
At each site visit, the subject will be questioned on the occurrence of uveitis flares since last 
visit. In case uveitis flares are confirmed by the subject the site will obtain the needed 
information from the subject's ophthalmologist containing the diagnosis of AU, the affected eye, 
location of the uveitis in the affected eye, duration, severity, and treatment provided.
Has been changed to: 
Subjects will be requested to contact an ophthalmologist when they experience an AU flare at 
any time during the study. The ophthalmologist will confirm the AU flare and determine the 
duration, severity, and treatment. The ophthalmologist will be provided with documentation to 
ensure all protocol-requested information is collected. The documentation will inform the 
ophthalmologist about the subject’s study participation and the requirements.
At each site visit, the subject will be questioned on the occurrence of uveitis flares since last 
visit. In case uveitis flares are confirmed by the subject the site will obtain the needed 
information from the ophthalmologist containing the diagnosis of AU, the affected eye, location 
of the uveitis in the affected eye, duration, severity, and treatment provided.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 107 of 113
The following information will be collected:
x Start and end date of each AU flare (episode)
 Start date: when subject experience first signs of the AU episode
 End date: when treatment of the AU is stopped
x Grading
 For uveitis flare, the highest grade noted during an episode of uveitis will be graded as 
follows:
Grade 0=None; Grade 1+=Faint; Grade 2+=Moderate, iris and lens details clear; 
Grade3+=Marked, iris and lens details hazy; Grade4+=Intense, fibrin or plastic aqueous; 
ND=Not done or not assessed; UNK=Unknown
 For cell count, the highest cell count noted during an episode of uveitis will be graded as 
follows:
Grade 0=<1 cell; Grade 0.5+=1-5 cells; Grade 1+=6-15 cells; Grade 2+=16-25 cells; 
Grade 3+=26-50 cells; Grade 4+=>50 cells; ND=Not done or not assessed; 
UNK=Unknown
x Treatment
Change #12 
Section 10.3 Adverse events of interest
The following text has been added as last paragraph:
Note : Potential Hy’s Law, defined as ≥3xULN alanine aminotransferase or aspartate 
aminotransferase with coexisting ≥2xULN total bilirubin in the absence of ≥2xULN alkaline 
phosphatase, with no alternative explanation for the biochemical abnormality, must ALWAYS 
be reported to UCB as an AE of interest (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should then be reported if an 
alternative etiology is identified during investigation and monitoring of the subject.
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 108 of 113
Change #13 
Appendix 16.2 ASAS classification criteria for axSpA
Imaging criteria
ASAS clinical criteria for axSpA
Sacroiliitis (MRI or radiographsa) plus ≥1 SpA 
feature
HLA-B27 plus ≥2 other SpA features
SpA featuresb
Inflammatory back painc
Arthritis 
Enthesitis (heel) 
Uveitis 
Dactylitis
Psoriasis
Crohn’s disease/ulcerative colitis
Good response to NSAIDs
Family history for SpA
HLA-B27
Elevated CRP
ASAS= Assessment of SpondyloArthritis International Society; axSpA=axial spondyloarthritis; 
CRP=C-reactive protein; MRI=magnetic resonance imaging; HLA-B27=human leukocyte antigen 
B27; NSAID=nonsteroidal anti-inflammatory drug; SpA=spondyloarthritis
* Active 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. 
** Family history for SpA and Good response to NSAIDs are excluded as SpA feature criteria. 
***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 <40 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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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 109 of 113
Has been changed to: 
ASAS classification criteria for axSpA
(for subjects with chronic back pain ≥3 months and age at onset <45 years)
Imaging criteria
ASAS clinical criteria for axSpA
Sacroiliitis (MRI or radiographsa) plus ≥1 SpA 
feature
HLA-B27 plus ≥2 other SpA features
SpA featuresb
Inflammatory back painc
Arthritis 
Enthesitis (heel) 
Uveitis 
Dactylitis
Psoriasis
Crohn’s disease/ulcerative colitis
Good response to NSAIDs
Family history for SpA
HLA-B27
Elevated CRP
ASAS=Assessment of SpondyloArthritis international Society; axSpA=axial spondyloarthritis; 
CRP=C-reactive protein; MRI=magnetic resonance imaging; HLA-B27=human leukocyte antigen 
B27; NSAID=nonsteroidal anti-inflammatory drug; SpA=spondyloarthritis
a Active 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 <40 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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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 110 of 113
17.3 
Protocol Amendment 3 
Rationale for the amendment
The purpose of this non-substantial amendment is to update the safety variables as a secondary 
safety variable and other safety variables.  
Modifications and changes 
Global changes 
x Updates have been made to the safety variables to include TEAEs as a secondary safety 
variable and blood pressure, physician examination, and clinical laboratory values as other 
safety variables.
x Study contact information was updated.
x Minor editorial and format corrections have been done to the protocol.
Specific changes 
Change #1 
Study Contact Information
Clinical Trial Biostatistician 
Name:
, MS
Address:
UCB Biosciences, Inc.
8010 Arco Corporate Drive
Raleigh, NC 27617
USA
Phone:
Fax:
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 111 of 113
Has been changed to: 
Clinical Trial Biostatistician 
Name:
Dr.
Address:
UCB Biosciences GmbH
Alfred-Nobel-Strasse 10
40789 Monheim
Germany
Phone:
Fax:
 
Change #2
Section 4.2: Safety variables
Safety variables to be assessed are:
x Adverse events (AEs)
x Blood pressure
x Physical examination
x Clinical laboratory values (hematology, biochemistry, and urinalysis)
Has been changed to:
Section 4.2: Safety variables
Section 4.2.1: Secondary safety variable
The secondary safety variable to be assessed is treatment-emergent adverse events (TEAEs).
Section 4.2.2: Other safety variables
The following other safety variables to be assessed are:
x Blood pressure
x Physical examination
x Clinical laboratory values (hematology, biochemistry, and urinalysis)
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 112 of 113
18 
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 COP
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UCB
22 Jan 2020
Clinical Study Protocol
Certolizumab pegol
AS0007
Confidential
Page 113 of 113
19 
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. 


Approval Signatures
Name:
as0007-protocol-amend-3
Version:
1. 0
Document Number:
CLIN-000148098
Title:
AS0007 Protocol Amendment 3
Approved Date:
27 Jan 2020
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 26-Jan-2020 15:35:31 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 27-Jan-2020 09:27:27 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 27-Jan-2020 09:34:22 GMT+0000
DACTED 
REDA
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SAP_001.pdf: 
UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 1 of 92
 
STATISTICAL ANALYSIS PLAN 
Study: AS0007
Product: Certolizumab pegol
MULTICENTER, OPEN-LABEL STUDY TO ASSESS THE EFFECTS OF CERTOLIZUMAB 
PEGOL ON THE REDUCTION OF ANTERIOR UVEITIS FLARES IN AXIAL 
SPONDYLOARTHRITIS SUBJECTS WITH A HISTORY OF ANTERIOR UVEITIS (C-
VIEW)
SAP/Amendment Number
Date
Final SAP
26 May 2017
Amendment 1
09 May 2018
Amendment 2
14 Nov 2018
Amendment 3
21 Feb 2020
Confidentiality Statement
Confidential
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 2 of 92
TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................5 
1 
INTRODUCTION .............................................................................................................9 
2 
PROTOCOL SUMMARY.................................................................................................9 
2.1 
Study objectives...........................................................................................................10 
2.1.1 
Primary objective.................................................................................................10 
2.1.2 
Secondary objectives ...........................................................................................10 
2.1.3 
Other objectives...................................................................................................10 
2.1.4 
Safety objective ...................................................................................................10 
2.2 
Study variables.............................................................................................................10 
2.2.1 
Efficacy variables ................................................................................................10 
2.2.1.1 
Primary efficacy variable ..........................................................................10 
2.2.1.2 
Secondary efficacy variables.....................................................................10 
2.2.1.3 
Other efficacy variables.............................................................................11 
2.2.2 
Safety variables....................................................................................................12 
2.2.2.1 
Secondary safety variable..........................................................................12 
2.2.2.2 
Other safety variables................................................................................12 
2.3 
Study design and conduct ............................................................................................12 
2.4 
Determination of sample size.......................................................................................15 
3 
DATA ANALYSIS CONSIDERATIONS......................................................................16 
3.1 
General presentation of summaries and analyses ........................................................16 
3.2 
General study level definitions ....................................................................................17 
3.2.1 
Analysis time points ............................................................................................17 
3.2.2 
Relative day .........................................................................................................17 
3.3 
Definition of Baseline values.......................................................................................18 
3.4 
Protocol deviations.......................................................................................................18 
3.5 
Analysis sets.................................................................................................................18 
3.5.1 
Enrolled Set .........................................................................................................19 
3.5.2 
Safety Set.............................................................................................................19 
3.5.3 
Full Analysis Set..................................................................................................19 
3.5.4 
Per Protocol Set ...................................................................................................19 
3.6 
Treatment assignment and treatment groups ...............................................................19 
3.7 
Center pooling strategy................................................................................................19 
3.8 
Coding dictionaries ......................................................................................................19 
3.9 
Changes to protocol-defined analyses .........................................................................19 
4 
STATISTICAL/ANALYTICAL ISSUES.......................................................................20 
4.1 
Adjustments for covariates ..........................................................................................20 
4.2 
Handling of dropouts or missing data..........................................................................20 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 3 of 92
4.3 
Interim analyses and data monitoring..........................................................................24 
4.4 
Multicenter studies.......................................................................................................25 
4.5 
Multiple comparisons/multiplicity...............................................................................25 
4.6 
Use of an efficacy subset of subjects ...........................................................................25 
4.7 
Active-control studies intended to show equivalence..................................................25 
4.8 
Examination of subgroups ...........................................................................................25 
5 
STUDY POPULATION CHARACTERISTICS.............................................................25 
5.1 
Subject disposition.......................................................................................................25 
5.2 
Protocol deviations.......................................................................................................26 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................26 
6.1 
Demographics ..............................................................................................................26 
6.2 
Other Baseline characteristics......................................................................................26 
6.3 
Medical history and concomitant diseases...................................................................27 
6.4 
Prior and concomitant medications..............................................................................28 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE...............................................28 
8 
EFFICACY ANALYSES ................................................................................................29 
8.1 
Statistical analysis of the primary efficacy variable(s)................................................30 
8.1.1 
Derivations of primary efficacy variable.............................................................30 
8.1.2 
Supportive and sensitivity analyses of the primary efficacy variable .................31 
8.2 
Statistical analysis of the secondary efficacy variable(s) ............................................32 
8.2.1 
Number of AU flares per 100 patient-years.........................................................32 
8.2.2 
Ankylosing spondylitis disease activity score (ASDAS) ....................................32 
8.2.3 
Bath ankylosing spondylitis disease activity index (BASDAI)...........................33 
8.2.4 
ASAS20, ASAS40, and ASAS PR......................................................................34 
8.2.5 
Physician’s global assessment of disease activity (PhGADA)............................34 
8.2.6 
Swollen and tender joint counts...........................................................................34 
8.2.7 
Patient’s global assessment of disease activity (PtGADA) .................................35 
8.2.8 
Total and nocturnal spinal pain............................................................................35 
8.2.9 
Bath ankylosing spondylitis functional index (BASFI).......................................35 
8.3 
Analysis of other efficacy variables.............................................................................36 
8.3.1 
Flare assessments.................................................................................................36 
8.3.2 
Extra-articular assessments..................................................................................36 
8.3.3 
Ankylosing spondylitis quality of life (ASQoL) .................................................36 
8.3.4 
ASAS Health Index (ASAS HI) Questionnaire...................................................37 
8.3.5 
Short-Form 36-Item Health Survey (SF-36)........................................................37 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS ..........................................37 
9.1 
Pharmacokinetics .........................................................................................................37 
9.2 
Pharmacodynamics ......................................................................................................37 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 4 of 92
10 SAFETY ANALYSES.....................................................................................................37 
10.1 
Extent of exposure .......................................................................................................37 
10.2 
Adverse events.............................................................................................................38 
10.3 
Clinical laboratory evaluations ....................................................................................40 
10.4 
Vital signs, physical findings, and other observations related to safety......................42 
10.4.1 
Vital signs ............................................................................................................42 
10.4.2 
Pregnancy testing.................................................................................................42 
10.4.3 
Physical assessments ...........................................................................................42 
10.4.4 
MRI assessments .................................................................................................42 
10.4.5 
Tuberculosis assessments ....................................................................................42 
10.4.6 
Chest x-ray...........................................................................................................43 
11 REFERENCES ................................................................................................................44 
12 APPENDICES .................................................................................................................45 
12.1 
APPENDIX 1: Compliance Ratio Calculation ............................................................45 
13 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) (IF 
APPLICABLE)................................................................................................................47 
13.1 
AMENDMENT 1.........................................................................................................47 
13.2 
AMENDMENT 2.........................................................................................................54 
13.3 
AMENDMENT 3.........................................................................................................63 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE.....................................................92 
LIST OF TABLES
Table 2‒1: 
Schedule of assessments ..................................................................................13 
LIST OF FIGURES
Figure 2‒1: 
Schematic diagram...........................................................................................15 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 5 of 92
LIST OF ABBREVIATIONS
AE
adverse event  
ALP 
alkaline phosphatase 
AS 
ankylosing spondylitis 
ASAS 
Assessment of SpondyloArthritis international Society 
ASDAS 
Ankylosing Spondylitis Disease Activity Score 
ASQoL 
Ankylosing Spondylitis Quality of Life 
ATC
Anatomic Therapeutic Chemical
AU  
anterior uveitis 
axSpA 
axial spondyloarthritis 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
BASMI
Bath Ankylosing Spondylitis Metrology Index
BMI
body mass index
BSA
body surface area
CII
clinically important improvement
CR
compliance ratio
CRD
compliance ratio based on duration
CRP 
C-reactive protein 
CZP 
certolizumab pegol 
DMARD
disease-modifying antirheumatic drug
EAER
exposure adjusted event rate
EAIR
exposure adjusted incidence rate
ES 
Enrolled Set 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 6 of 92
FAS 
Full Analysis Set 
FDA
Food and Drug Administration
FU 
Follow-Up 
HI
Health Index
HLA-B27 
human leukocyte antigen B27 
HLT
high level term
HRQoL 
health-related quality of life 
IBD 
inflammatory bowel disease 
ICF
informed consent form 
ICH 
International Council for Harmonisation 
ID 
inactive disease 
IGRA
interferon-gamma release assay
IPD
important protocol deviations
IWRS 
interactive web response system 
LLN
lower limit normal
LTBI 
latent tuberculosis infection 
MCID
minimal clinically important difference
MedDRA
Medical Dictionary for Regulatory Activities
MH
markedly abnormal high
MI
major improvement
ML
markedly abnormal low
mNY 
modified New York (criteria) 
MRI 
magnetic resonance imaging 
nr-axSpA 
nonradiographic axSpA 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 7 of 92
NRS 
Numerical Rating Scale 
NSAID
nonsteroidal anti-inflammatory drug
PhGADA 
Physician’s Global Assessment of Disease Activity 
PPS
Per Protocol Set
PR
partial remission
PT
preferred term
PtGADA
Patient’s Global Assessment of Disease Activity
Q2W 
every 2 weeks (every other week) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
sc 
subcutaneous(ly) 
SD
standard deviation
SF-36 
Short-Form 36-Item Health Survey 
SIJ 
sacroiliac joint  
SJC
swollen joint count
SpA 
spondyloarthritis 
SOC
System Organ Class
SS 
Safety Set 
TEAE
treatment emergent adverse event
TB 
tuberculosis 
TJC
tender joint count
TNF
tumor necrosis factor
ULN
upper limit normal
WD 
withdrawal 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 8 of 92
WHO-DD
World Health Organization Drug dictionary
REDACTED COPY 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 9 of 92
1
INTRODUCTION
This Statistical Analysis Plan (SAP) describes the analysis of study AS0007. It includes the final 
analysis when all data including follow-up period are available, as well as the formal interim 
analysis defined in the protocol, which will take place when all Week 48 data are available.
The SAP is based on Amendment 3 of the Clinical Study Protocol, dated 22 Jan 2020.
The content of this SAP is in compliance with the International Conference on Harmonization 
(ICH) / Food and Drug Administration (FDA) E9 Guidance documents.
2
PROTOCOL SUMMARY
AS0007 is a multicenter, open-label, Phase 4 study to evaluate the effects of certolizumab pegol 
(CZP) on the incidence of anterior uveitis (AU) flares per year in subjects with both active axial 
spondyloarthritis (axSpA) and a history of AU by comparing the historical AU flare rate that 
occurred prior to CZP treatment with the AU flare rate occurring while under CZP treatment.
Approximately 130 subjects will be screened in Europe in order to enroll 86 subjects into the 
study.
The study duration from the start of treatment will be 96 weeks from Baseline onwards, and a 
follow-up visit will be performed at Week 104; 10 weeks after the last dose administration at 
Week 94.
The study includes 3 periods as follows: 
x
Period 1 (Screening Period): 1 to 5 weeks before Baseline
Subjects will be informed about the study and sign the informed consent form (ICF). Eligibility 
will be evaluated and assessments will be performed. The Screening Period should be kept as 
short as possible but can be extended to 5 weeks if certain medications need to be washed out or 
to allow to obtain information from the subject’s ophthalmologist. For subjects who start a 
prophylactic treatment for latent tuberculosis infection (LTBI) the Screening Period can be 
extended up to 12 weeks.
x
Period 2 (Treatment Period): Week 0 to Week 96 
Eligible subjects will receive a dose of CZP 400mg subcutaneously (sc) at Baseline, Week 2, and 
Week 4 followed by CZP 200mg sc every 2 weeks (Q2W) starting at Week 6 until Week 94.
All subjects will be trained at the beginning of the study on self-administration before the 
subjects start self-administration with the study drug (relative or caregiver may also perform the 
injections). The injection schedule will provide the sequence of self-administration and site visits 
including injection at the site.
x
Period 3 (Follow-Up [FU] Period): 10 weeks from the final dose of study medication 
received
All subjects will have a FU Visit at Week 104 or earlier in case of an early withdrawal (WD), 
10 weeks after the final administration of CZP administration received within the study.
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 10 of 92
A Week 48 analysis will be performed after all subjects have either completed the Week 48 Visit 
or have prematurely withdrawn prior to the Week 48 Visit. The final analysis will be conducted 
at the end of the study after all study data is locked.
2.1
Study objectives
The following key definition is provided as a reference for understanding the study objectives 
and is used throughout the document.
A flare is defined as being a new episode of AU that, based on the judgment of an 
ophthalmologist, requires specific treatment. A flare is considered a new episode if a gap of at 
least 3 months occurs between 2 flares.
2.1.1
Primary objective
The primary objective of the study will be to demonstrate the effect of CZP treatment on the 
reduction of AU flares in subjects with active axSpA and a documented history of AU.
2.1.2
Secondary objectives
The secondary objectives of the study will be to assess the effect of CZP treatment on:
x
The reduction of AU flares in subjects with active axSpA having at least 1 documented 
history of AU within 12 months prior to Baseline
x
AxSpA disease activity
2.1.3
Other objectives
The other objectives of the study will be to assess the effect of CZP treatment on:
x
Physical function
x
Signs and symptoms of axSpA

Morning stiffness

Fatigue

Extra-articular manifestations of axSpA 
x
Duration and severity of AU flares
2.1.4
Safety objective
The safety objectives of the study will be to evaluate the safety and tolerability of CZP therapy.
2.2
Study variables
2.2.1
Efficacy variables
2.2.1.1
Primary efficacy variable
The primary efficacy variable will be the count of distinct episodes of AU flares during the 
Treatment Period.
2.2.1.2
Secondary efficacy variables
The following secondary efficacy variables will be assessed at Week 48 and Week 96:
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 11 of 92
x
Number of AU flares per 100 patient-years in subjects with active axSpA and a history of 
AU
x
Number of AU flares per 100 patient-years in subjects with active axSpA and at least 1 AU 
episode within 12 months prior Baseline
x
Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
x
Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
x
Assessment of ASAS 20, 40, 5/6, and partial remission (PR) response rates
x
Change from Baseline in tender and swollen joint count (44 joint count); Physician’s Global 
Assessment of Disease Activity (PhGADA).
x
Change from Baseline in the respective components of the ASAS response criteria, assessed 
by:

Patient’s Global Assessment of Disease Activity (PtGADA)

Pain assessment (total spinal pain Numerical Rating Scale [NRS])

Function (represented by Bath Ankylosing Spondylitis Functional Index [BASFI])

Inflammation (the mean of the BASDAI questions 5 and 6 concerning 
2.2.1.3
Other efficacy variables
The following other efficacy variables will be assessed at the timepoints indicated in Table 2‒1 :
x
Duration of AU flares 
x
Severity of AU flares
x
Change from Baseline in ASDAS
x
Change from Baseline in BASDAI
x
ASAS 20, 40, 5/6, and PR response rates
x
Change from Baseline in tender and swollen joint count (44 joint count); Physician’s Global 
Assessment of Disease Activity (PhGADA)
x
Change from Baseline in the respective components of the ASAS criteria, assessed by:

PtGADA

Pain assessment (total spinal pain NRS)

Function (represented by BASFI)

Inflammation (the mean of the BASDAI questions 5 and 6 concerning 
)
x
Change from Baseline in ASDAS disease activity (clinical improvement [CI], major 
improvement [MI], inactive disease [ID], clinically important improvement [CII]), and 
BASFI) (including Weeks 48 and 96)
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 12 of 92
x
Change from Baseline in 
 (NRS) (from BASDAI) (including Weeks 48 and 96)
x
Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) (including 
Weeks 48 and 96)
x
Change from Baseline in ASAS Health Index (HI) questionnaire (including Weeks 48 and 
96)
x
Change from Baseline in Short-Form 36-Item Health Survey (SF-36) (including Weeks 48 
and 96)
x
Number of inflammatory bowel disease (IBD) exacerbations
x
Number of psoriasis exacerbations (in subjects with concurrent psoriasis)
2.2.2
Safety variables
2.2.2.1
Secondary safety variable
The secondary safety variable to be assessed is treatment-emergent adverse events (TEAEs).
2.2.2.2
Other safety variables
The following other safety variables to be assessed are: 
x
Blood pressure
x
Physical examination
x
Clinical laboratory values (hematology, biochemistry, and urinalysis).
2.3
Study design and conduct
AS0007 is a multicenter, open-label, Phase 4 study to evaluate the effects of CZP on the 
incidence of AU flares per year in subjects with both active axSpA and a history of AU by 
comparing the historical AU flare rate that occurred prior to CZP treatment with the AU flare 
rate occurring while under CZP treatment.
The study will be conducted in Europe. Approximately 130 subjects are planned to be screened 
in order to enroll 86 subjects into the study. The Schedule of Assessments is shown in Table 2‒1.
A study schematic diagram is presented Figure 2‒1.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 13 of 92
Table 2‒1:
Schedule of assessments
Study Period
Period 
1
(Scree-
ning)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
36
48
60
72
84
96/ 
WD
104
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Written informed 
consentb
X
Assessments for 
inclusion/ 
exclusion criteria
X
X
Demographic data
X
Medical history 
(including axSpA 
history, and 
tobacco use) and 
concomitant 
diseases 
X 
Prior and 
concomitant 
medicationc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Uveitis history
X 
Uveitis flare 
evaluation
 
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examinatione
X 
X
X
X
X
X
X
X
X
X
X
X
X
Extra-articular 
assessmentsf
X
X
X
X
X
X
X
X
X
X
Hematology/ 
urinalysis/
biochemistry/ 
Xg 
X
X
X
X
X
X
X
X
X
X
X
CRP
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testingh
X 
X
X
X
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X
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X
X
X
X
X
X
X
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BASDAI
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X
X
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X
X
X
X
X
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X
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BASFI
 
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X
X
X
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X
X
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ASQoL
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X
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X
X
X
X
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ASAS HI 
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X
X
X
X
X
X
X
X
X
X
SF-36
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X
X
X
X
X
X
X
X
X
X
PtGADA
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X
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 14 of 92
Table 2‒1:
Schedule of assessments
Study Period
Period 
1
(Scree-
ning)
Period 2 (Open-Label)
Period 
3
FU
Week (W)
Protocol Activity
-5 to -1a
0
BL
2
4
12
24
32
36
48
60
72
84
96/ 
WD
104
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Total and
nocturnal spinal 
pain
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
PhGADA
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
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug sc 
injectionsm
X
X
X
X
X
X
X
X
X
X
X
Schedule 
appointment for 
next visit
X
X
X
X
X
X
X
X
X
X
X
X
X
AE=adverse event; AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; 
ASQoL=Ankylosing Spondylitis Quality of Life; axSpA= axial spondyloarthritis; BASDAI=Bath Ankylosing Spondylitis 
Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BL=Baseline; CRP=C-reactive protein; 
FU=Follow-up; HI=Health Index; HLA-B27= human leukocyte antigen B27; IBD=inflammatory bowel disease; 
IWRS=Interactive Web Response System; LTBI=latent tuberculosis infection; mNY=modified New York (classification 
criteria); MRI=magnetic resonance imaging; nr-axSpA=nonradiographic axSpA; PhGADA=Physician’s Global Assessment of 
Disease Activity; PtGADA=Patient’s Global Assessment of Disease Activity; Q2W=every 2 weeks (every other week); 
sc=subcutaneous(ly); SF-36=Short-Form 36-Item Health Survey; SIJ=sacroiliac joint; TB=tuberculosis; WD=Withdrawal
a For subjects with LTBI who initiate a prophylactic treatment and need to have 8 weeks of prophylactic treatment prior to 
randomization, the Screening Period can be extended to 12 weeks. For other subjects, the Screening Period should be kept as 
short as possible, but can be up to 5 weeks if certain medications need to be washed out or to allow to obtain information from 
the subjects’ ophthalmologist.
b Informed consent: prior to any study activities, subjects will be asked to read and sign the informed consent form.
c Past medications will recorded at Screening. Concomitant medications will be recorded at all other visits.
d Pulse rate, systolic and diastolic blood pressures, and temperature are to be measured at Screening and Baseline, thereafter 
systolic and diastolic blood pressures are to be measured. 
e Weight is to be measured at Screening, Baseline, Week 48, and at completion at Week 96/WD Visit. Height will be measured 
at the Baseline Visit only.
f Extra-articular assessments includes the number of IBD exacerbations and number of psoriasis exacerbations (in subjects with 
concurrent psoriasis)
g Testing to rule out hepatitis B core antibody, hepatitis B surface antigen, hepatitis B surface antibody, antibodies to hepatitis C, 
and antibodies to human immunodeficiency virus at Screening only. Testing for HLA-B27 at Screening, only if not performed 
before.
h Pregnancy testing for women of childbearing potential will be serum testing at the Screening Visit and urine dipstick testing at 
Baseline and Week 96/WD Visit and the FU Visit (10 weeks after the final dose of study drug). 
i Chest x-ray used for screening must have been done within 3 months prior to the 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). If no chest x-
ray is available within the 3 months prior to the Screening Visit, the x-ray can be done during the Screening Period.
j QuantiFERON TB GOLD test. The TB tests will be repeated at Week 48 and 96 (or at WD Visit if medically indicated) for 
subjects with previously negative TB test result.
k For subjects with nr-axSpA, an MRI of the SIJs is to be performed during the Screening Period. An MRI performed ≤3 months 
prior to the Baseline Visit may be used as the Baseline. An MRI assessment is not needed for patients with AS.
l AS subjects must have evidence of sacroiliitis on x-ray taken prior to Baseline meeting the mNY classification criteria 
according to the Investigator. If not available, this x-ray is to be taken during the Screening Period. If an x-ray was performed 
prior to the Screening Visit and the mNY classification criteria were met, the x-ray is not to be repeated.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 15 of 92
m Onsite study drug administration will occur after all other visit assessments are completed and laboratory samples are drawn. 
Study drug injections will occur at home Q2W on Weeks 6, 8, and 10, 14 to 22, 26 to 30, 34, 38 to 46, 50 to 58, 62 to 70, 74 to 
82, and 86 to 94. At all visits, an even number of syringes (2 per box) will be assigned (eg, at Week 4 syringes will be assigned 
for Weeks 6, 8, and 10; 1 syringe will be returned by the subject at Week 12).
Figure 2‒1: Schematic diagram
axSpA=axial spondyloarthritis; CZP=certolizumab pegol; LD=loading dose; Q2W=every 2 weeks
The aim of the study is to evaluate the flare rate of AU before the start of CZP treatment 
compared to that of a period with CZP treatment. Since the occurrence of flare is both subject 
and disease specific, each subject should act as his/her own control. Because an untreated uveitis 
flare can cause severe eye complication, it was deemed necessary to treat all subjects with an 
active drug.
Therefore, 1 treatment arm with 1 set of subjects is deemed the right approach to allow for the 
comparison of the history of flare occurrence with the flare occurrence on a biological treatment 
in the same subjects. The dose of CZP used in this study is the same as per label to treat axSpA 
subjects, which has been shown to be 
 and effective for reducing the main axSpA symptoms.
2.4
Determination of sample size
Based on results from a previous study with CZP in axSpA subjects (AS001), the AU flare rate 
while treated with CZP is estimated to be 14.6 events per 100 subject-years of exposure. 
Assuming the rate while treated with CZP represents a reduction in the flare rate of 
approximately 50%, the AU flare rate for the prestudy period prior to initiation of CZP is 
estimated to be 29.2 events per 100 subject-years of exposure. A conservative estimate of the 
sample size for this study is obtained via derivation of the per treatment-group sample size for 
Poisson regression based on the approach for a 2-group setting initially described by Signorini 
(1991) and implemented within SAS (Hu, 2008). Assuming an average follow-up period of 1.5 
years with 2-sided α-level=0.049 for the final analysis of the primary efficacy variable, a sample 
size of N=86 subjects per treatment group will have 80% statistical power for a 2 group 
comparison, corresponding to a total sample size of N=86 subjects for this study with 1 treatment 
group. Due to the expected increase in statistical efficiency from the fact that each subject serves 
as his/her own control in the primary efficacy analysis, the actual power for this study is assumed 
to be >80 percent.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 16 of 92
3
DATA ANALYSIS CONSIDERATIONS
3.1
General presentation of summaries and analyses
The statistical analyses will be performed by Chiltern. Computations and generation of outputs 
will be performed using SAS® (Statistical Analysis System, SAS-Institute, Cary, NC, USA) 
Version 9.3 or above. All tables and listings will use Courier New font size 9.
For continuous data in general, summary statistics (n [number of available measurements], 
arithmetic mean, standard deviation (SD), median, minimum, and maximum) will be presented.
For selected variables, the first (25th percent) quartile (Q1) and the third (75th percent) quartile 
(Q3) may also be presented (for patient reported outcomes).
Mean, SD, median and quartiles will be displayed to 1 more decimal place than collected in the
source data. Derived variables in general will display the mean, SD and median to 1 more 
decimal place than the variables used in the derivation (i.e. a change from Baseline will be 
reported to the same precision as the Baseline data). However, a special rule can be defined as 
needed for appropriate reporting.
For descriptive statistics of continuous variables by visit, the change from Baseline and actual 
value at the given time point will be displayed. The change from Baseline is the post-Baseline 
value minus the Baseline value. If the Baseline or post-Baseline value is missing, then the 
change from Baseline is set to missing. Percent change from Baseline is the change from 
Baseline divided by Baseline and multiplied by 100. If the Baseline value is 0 and the post-
Baseline value is also 0, then the percent change from Baseline is set to 0. If the Baseline value is 
0 and the post-Baseline value is non-zero, then the percent change from Baseline is set to 
missing. If the Baseline value is missing, the percent change from Baseline is set to missing.
Frequency tables (frequency counts and percentages) will be presented for categorical data. If 
there are no missing values then the missing row can be removed. If there are missing values 
(including missing a single assessment or entire visit), then include the missing row with the 
frequency count and percentage. If there are no subjects in a specific CRF category, then that 
row will be retained and 0 presented in the table. In general, percentages will be calculated based 
on the utilized analysis set. However, in the case of subgroup analyses, the N of the subgroup 
will be used as denominator.
Unless stated otherwise, all inferential statistical tests will be 2-sided and conducted at the 0.05 
alpha level. Adjustment for multiplicity is described in Section 4.5. P-values for secondary 
efficacy variables are nominal. P-values will be presented to 3 decimal places and any values 
below 0.001 should be displayed as “<0.001”.
All data in the database (SDTM and ADaM) will be presented in by-subject data listings, and 
sorted by subject number, parameter (where applicable), and visit (where applicable). For listings
including subjects that were not treated, these subjects will be shown first in the listing, ordered 
by subject number. All listings will include repeated and unscheduled measurements. Such 
measurements will appear in chronological order together with the scheduled visits, i.e., a 
repeated measurement will appear directly after the visit and time relative to dosing, for which 
the repeat measurement was performed. In all the listings dates will be presented in the format 
‘YYYY-MM-DD’ and times will be presented in 24h clock format as ‘hh:mm’ or ‘hh:mm:ss’ 
where appropriate.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 17 of 92
All tabulations will be sorted by parameter and visit. Only scheduled visits will be included in 
the tabulation. Categorical data will be summarized by visit, using the number and percentage of 
subjects in each category. Percentages will be based on the corresponding population size (i.e., 
the denominator of percentages should match the sample size in the column header), unless 
otherwise noted via footnote in the applicable summary table. Percentages will be presented to 1 
decimal place. For data points with n=0 (i.e., no subjects in the applicable category), no value for 
percentage of subjects will be displayed.
3.2
General study level definitions
3.2.1
Analysis time points
The study includes 3 periods as follows: 
x
Period 1 (Screening Period): 1 to 5 weeks before Baseline
The pre-treatment period (Screening period) of the study is the period prior to a subject’s first 
dose of study medication intake. This period starts at the Screening visit (week -5 to -1 day, 
extended to week -12 for subjects who start a prophylactic treatment for LTBI) and ends at the 
Baseline visit (Week 0) up to the time of first study medication administration (exclusive). 
Unless specific time information is available to indicate that a Screening or Baseline visit 
assessment was performed after a subject’s first study medication administration, most 
assessments will be attributed to the Screening period. Exceptions to this are AEs that start on 
Baseline visit, as they will be attributed to the Treatment Period.
x
Period 2 (Treatment Period): Week 0 to Week 96 
The treatment period begins at the Baseline visit (Week 0) at the time of first study medication 
administration (inclusive) and ends at Week 96/WD visit. Premature withdrawal visit 
assessments will be assigned to the next scheduled visit following the last visit where 
assessments are available. All visit measurements, even violating the visit window, will be 
utilized for the respective visit as long as they are in the proper sequence. Subjects will be 
classified as completing the study if they complete the Week 96 Visit without early withdrawal 
of the study. This is regardless of whether they attend the Follow-up visit. 
x
Period 3 (FU Period): 10 weeks from the final dose of study medication received
The Follow-up visit will take place 10 weeks after the last dose of study medication. That is 
either 8 weeks after the Week 96 visit for subjects completing the study, or up to 10 weeks after 
the WD visit for withdrawn subjects.
3.2.2
Relative day
The relative day will be included in different listings and will be calculated as follows:
x
If the start (stop) date occurred on or after the first dose, but prior to the drug stop date, 
relative day is calculated as start (stop) date minus first dose date + 1.
x
If the start (stop) date occurred after the last dose of drug, the relative day to the most recent 
dose is calculated as start (stop) date minus most recent dose date. The relative day in this 
situation should be preceded by a ‘+’.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 18 of 92
x
If the start (stop) date occurred before the first dose, the relative day is calculated as start 
(stop) date minus first dose date. The relative day in this situation should be preceded by a 
‘-’.
For AEs, relative days for start and stop dates will be calculated as the number of days since the 
first injection of the medication. For non-treatment emergent AEs, relative day of onset will be 
negative if the event started and stopped before the first dose. Relative day will only be 
computed for fully completed dates and will be missing for partial dates.
3.3
Definition of Baseline values
Unless otherwise specified, the last valid measurement before study medication administration 
will be utilized as Baseline value. For almost all variables, this will be the assessment made at 
the Baseline visit. However, for some variables, assessments may be scheduled for Screening 
only and not for Baseline. In this case the screening value will be utilized as baseline value. If a 
baseline measurement is missing, and a screening value available, the screening value will be 
utilized as Baseline instead. If a scheduled Baseline assessment is taken on the same day as first 
administration of study medication, it will be used as Baseline, irrespective of the time of the 
assessment relative to the first administration of study medication.
3.4
Protocol deviations
Important protocol deviations (IPD) are deviations from the protocol which could potentially 
have a meaningful impact on study conduct, on the safety for an individual subject, or on the 
primary efficacy outcome for an individual subject. The criteria for identifying important 
protocol deviations will be defined within the specification of the IPD document. Important 
protocol deviations will be reviewed as part of the ongoing data cleaning process and all
important deviations will be identified and documented prior to database lock.
Important protocol deviations will be identified and classified by the deviation types defined in 
the IPD document. A listing of all important protocol deviations identified at the Data Evaluation 
Meeting will be presented for all subjects in the SS, and will include deviation type and 
description. The number and percentage of subjects in the SS with important protocol deviations 
will be summarized overall.
The following deviation types, and further deviation types, may be included in the IPD:
x
Inclusion criteria
x
Exclusion criteria
x
Withdrawal criteria
x
Exposure
x
Non-compliance
x
Prohibited concomitant medications
3.5
Analysis sets
The main analysis sets defined for this study are the Enrolled Set (ES) and the Safety Set (SS). In 
addition, a Full Analysis Set (FAS) is defined for the unexpected case of missing Baseline values 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 19 of 92
for the primary efficacy variable. A Per Protocol Set (PPS) is added for additional analysis of the
primary efficacy variable only. 
3.5.1
Enrolled Set
The ES will consist of all subjects who have given informed consent.
3.5.2
Safety Set
The SS will consist of all subjects in the ES who have received at least 1 dose of study 
medication.
Safety variables, and also efficacy variables, will be summarized using the SS.
3.5.3
Full Analysis Set
The FAS will consist of all subjects in the SS with non-missing Baseline value for the primary 
efficacy variable, i.e. AU flare incidence data from pre-study period.
In case the FAS differs from the SS, the efficacy analysis will be conducted using the FAS
instead of the SS.
3.5.4
Per Protocol Set
The PPS will consist of all subjects in the SS, or in the FAS if applicable, which do not have any 
important protocol deviation affecting the primary efficacy variable. Subjects with at least one 
important protocol deviation affecting the primary efficacy variable will be excluded from the 
PPS.
3.6
Treatment assignment and treatment groups
At Baseline, eligible subjects will be assigned to the study treatment CZP. Certolizumab pegol 
will be administered as 400mg at Baseline and Weeks 2 and 4 followed by 200mg Q2W (starting 
at Week 6 until Week 94). As there is a single treatment arm in this study, all subjects will be 
presented together in a single treatment group (eg, as “CZP”). For presentation purposes, the 
term CZP will be used.
3.7
Center pooling strategy
All results will be summarized across centers and will not be stratified by center. No pooling of 
centers is planned for this study.
3.8
Coding dictionaries
All AEs, concomitant diseases, and medical history will be coded for analysis according to the 
Medical Dictionary for Regulatory Activities (MedDRA)® coding dictionary, version 19.0. Prior 
and concomitant medications will be coded for analysis using the World Health Organization 
Drug dictionary (WHO-DD), version SEP/2015.
3.9
Changes to protocol-defined analyses
The analysis of Axial SpondyloArthritis international Society response ASAS5/6 will not be 
performed as described in the clinical study protocol, because one main component for spinal 
mobility, the Bath Ankylosing Spondylitis Metrology Index (BASMI), is not collected in the 
data.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 20 of 92
The ASAS 5/6 response is defined as at least 20% improvement in 5 of the following 6 domains:
•
Patient’s Global Assessment of Disease Activity
•
Pain assessment (the total spinal pain NRS score)
•
Function (represented by the Bath Ankylosing Spondylitis Functional Index (BASFI))
•
Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index 
(BASDAI) questions 5 and 6) 
)
•
Spinal mobility (lateral lumbar flexion measured by BASMI)
•
CRP as more objective measures
As the BASMI is not collected, and there is no alternative measure of spinal mobility available in 
the study data, the complete component for spinal mobility is missing. Therefore the ASAS 5/6 
response criterion cannot be calculated, and the analysis of the secondary efficacy variable 
ASAS 5/6 has to be dropped. 
The clinical study protocol does not mention a PPS. This analysis set has been added, in order to 
additionally perform the primary efficacy analysis on the subset of protocol-compliant subjects. 
In the calculation of ASDAS (Section 9.1.2 of the protocol), the CRP component was written as 
“0.579 × (natural logarithm of the CRP [mg/L] + 1)”, but should have been “0.579 × (natural 
logarithm of the (CRP [mg/L] + 1))”.
For BASDAI (Section 9.1.3 of the protocol), the protocol stated “The BASDAI is a validated 
self-reported instrument which consists of six 10-unit horizontal NRSs to 
over the last week”. However the 
severity and duration are only measured for 
, the others are measured for 
severity only.
In Section 9.1.4 of the protocol, the pain assessment component of ASAS20/40/PR was defined 
as “the average of total and nocturnal spinal pain NRS scores”, but this should be defined as total 
spinal pain NRS score only.
ASDAS Clinical improvement was detailed as an “other” efficacy variable, but no definition was 
given. As there is no well-accepted definition, this variable has not been included in the analysis.
In Section 12.7 of the protocol, it stated that the interim analysis would use α=0.0001 and so the 
final analysis would use α=0.049. This should have said that α=0.001 would be used for the 
interim analysis.
4
STATISTICAL/ANALYTICAL ISSUES
4.1
Adjustments for covariates
Statistical models may be adjusted for covariates. Any such adjustments will be described in the 
context of the analyses to be performed.
4.2
Handling of dropouts or missing data
Analysis is based on observed case only.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 21 of 92
If the Baseline value is missing, the Screening value may be used as the Baseline. In general, if 
no measurement is available prior to receiving study medication, then the Baseline value is 
treated as missing, and will not be imputed. 
Premature withdrawal visits should be assigned to what would have been the next scheduled visit 
for the particular assessment that is being summarized. If a premature withdrawal visit occurs on 
the same date as a scheduled visit, then the assessments will be summarized with the scheduled 
visit.
Safety variables
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or 
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed
values will be displayed in data listings).
x
Missing start day, but month and year present: If the start of study medication occurred in the 
same month and year as the occurrence of the AE/concomitant medication, the start day of 
the event/concomitant medication will be assigned to the day of first intake of study 
medication. Otherwise the start day will be set to the 1st day of the month.
x
Missing start day and month, but year present: If the start of study medication occurred in the 
same year as the occurrence of the AE/concomitant medication, the start day and month will 
be assigned to the date of first intake of study medication. Otherwise the start day and month 
will be set to January 1st.
x
If start day, month, and year are missing, start date will be replaced by the date of first study 
drug administration or by the first day of January of the year of the end date, if the first 
administration date is after the end date.
x
Missing end day, but month and year present: The end day will be set to the last day of the
month.
x
Missing end day and month, but year present: If the maximum of the subject’s date of study 
termination or the date equivalent to 70 days after the subject’s last intake of study 
medication is the same year as the occurrence of the AE/Concomitant medication, then the 
end day and month will be set to the maximum of the date of study termination or the date 
equivalent to 70 days after last intake of study medication. Otherwise the end day will be set 
to December 31st of the given year.
Efficacy variables
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 days 
prior to Baseline until Baseline. The on-study period for the interim analysis is starting from 
Baseline until week 48, i.e. until study day 336. 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 22 of 92
For the final analysis, the pre-study period is starting 24 months prior to Baseline, i.e. 730 days 
prior to Baseline until Baseline. The on-study period for the final analysis is starting from 
Baseline until week 96, i.e. until the date of the Week 96 or discontinuation visit. In addition, 
sensitivity and supportive analyses use different definitions (as defined in Section 8.1.2).
Pre-study period:
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare in the 
same eye, and the end date is clearly greater than end date of previous flare, then impute 
with the end date of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare in the same eye, then use the latest date of both 
for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare in the same eye, then impute 
with the end date of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare in the same eye, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within the pre-study period. Then the maximum (latest) of start 
date of pre-study period and end date of previous flare will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

Month and year are the same as month and year of the start date of subsequent pre-study 
flare in the same eye before Baseline, then impute with the start date of subsequent pre-
study flare. 

In the case that month and year of the end date of pre-study period is the same month and 
year of the start date of subsequent pre-study flare in the same eye, then use the earliest 
date of both for imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 23 of 92

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 

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
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of subsequent pre-study flare in the same eye, then use the earliest date of both for 
imputation.
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred within the pre-study period (of 2 years prior to baseline). Then the 
minimum (earliest) of end date of pre-study period (i.e. the day prior to treatment start date),
the day prior to start date of subsequent pre-study flare in the same eye, or the start date plus 
the median duration of flare in that subject will be considered. The median duration of flare 
is determined from all flares recorded for that subject that have complete start and end dates 
(regardless of eye), including any flares prior to or during the pre-study period and on-study 
period.
On-study period (Baseline until end of treatment):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of study medication, then 
impute with the start date of study medication. 

Month and year are the same as month and year of the end date of previous on-study flare
in the same eye, and the end date is clearly greater than end date of previous on-study 
flare in the same eye, then impute with the end date of previous on-study flare in the 
same eye.

In the case that month and year of the start date of study medication is the same month 
and year of the end date of previous on-study flare in the same eye, then use the latest 
date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of study medication, then impute with the start 
date of study medication.

Year is the same as year of the end date of previous on-study flare in the same eye, then 
impute with the end date of previous on-study flare in the same eye.

In the case that year of the start date of study medication is the same year of the end date 
of previous on-study flare in the same eye, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred after treatment start during the on-study period. Then the 
maximum (latest) of start date of study medication and end date of previous on-study flare in
the same eye will be considered.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 24 of 92
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of on-study period, then 
impute with the end date of on-study period. 
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flare in the same eye, then impute with the start date of subsequent on-study flare in the 
same eye.
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date of both for imputation.
x
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following conditions apply:

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of on-study period. 

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then impute with the start date of subsequent on-study flare in the same eye.
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subsequent on-study flare in the same eye, then use the earliest date of both for 
imputation.
x
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date that the flare occurred after treatment start during the on-study period. Then the start 
date of subsequent on-study flare in the same eye will be considered. Otherwise it will be 
assumed to be ongoing.
4.3
Interim analyses and data monitoring
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. 
An interim analysis is planned to be conducted after the last subject has completed the Week 48 
assessment. That is when each treated subject has completed the Week 48 Visit, or withdrawn 
prematurely. All data collected until the database cut-off date will be included. With this interim 
analysis, first study results will be available already about one year before the final analysis of 
the study. There is no intention to stop the study early for efficacy or for futility. The interim 
summaries and listings will be based on the same shells as for the final analysis, unless otherwise 
stated. The interim listings will include all data collected up to Week 48. The summary tables 
presenting results by visit will only consider results up to Week 48 Visit for the interim analysis.
Summary tables of results not provided by visit, e.g. adverse events, will not include events or 
medication that started after the Week 48 Visit. Data collected after Week 48 will not be 
presented in the interim analysis.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 25 of 92
The length of pre-study period and on-study period for collection of AU flares data will be 48 
weeks for the interim analysis, and will be 96 weeks for the final analysis. The analysis based on 
period length of 48 weeks will be repeated for the final analysis.
No separate SAP will be created for the interim analyses, as all analyses will be covered within 
this SAP, and within the corresponding display specifications. In general, the interim analysis 
will follow the same specifications as the final analysis, unless stated differently in the 
corresponding sections. The interim analysis will include a subset of tables and listings that will 
be marked in the display specifications.
An additional interim data-cut might be needed to support a regulatory submission in nr-axSpA
or axSpA.
4.4
Multicenter studies
The data from all centers will be pooled for the purposes of the final analyses. There will be no 
formal statistical evaluation of the effect of center on the results obtained.
4.5
Multiple comparisons/multiplicity
Although there is no intention to stop the study early due to efficacy or futility on the basis of the 
interim results, α=0.001 will be spent in conjunction with this formal interim review of the data 
(Haybittle, 1971), and the final analysis of the primary efficacy variable will be conducted at the 
reduced 2-sided α-level of 0.049.
4.6
Use of an efficacy subset of subjects
Not applicable.
4.7
Active-control studies intended to show equivalence
Not applicable.
4.8
Examination of subgroups
The primary efficacy variable will be summarized using the following subgroups:
x
Gender (Male, Female)
x
Age (<median, >=median)
x
axSpA subpopulation as determined by the investigator (Ankylosing Spondylitis, non-
radiographic axial spondyloarthritis)
A Poisson regression model as described for the primary analysis will be used including terms 
for the subgroup and the subgroup by treatment period interaction. The results will be presented, 
but no p-values will be given.
5
STUDY POPULATION CHARACTERISTICS
5.1
Subject disposition
Subject disposition will be listed for all subjects screened and will include the following 
information: subject status (screen failure, completed or discontinued), date of informed consent, 
date of first and last dose of study medication (including relative day for last dose), date of 
premature study termination (if applicable) and primary reason for study termination (if 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 26 of 92
applicable). For screen failures the date and reason for screen failure will be listed. Subject 
disposition will be summarized for all subjects screened including the reasons for screen failure. 
Subject disposition will also be summarized for the Enrolled Set including the reasons for 
discontinuation of study and/or study medication. Study eligibility criteria will be listed and a 
separate listing of subjects who did not meet the eligibility criteria will be presented. A listing of 
study visit dates will be presented by subject including the relative study day with respect to 
treatment start for each visit.
5.2
Protocol deviations
Protocol deviations will be identified and documented as described in Section 3.4. The 
assignment of subjects to each of the analysis sets will be listed for all subjects screened. In 
addition, a listing of subjects excluded from the analysis sets will be presented including the 
reasons for exclusion; this listing will be based on the Enrolled Set.
6
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS
6.1
Demographics
Tables with descriptive statistics and listings will be given for the demographic variables age (at 
time of informed consent), gender, weight and height at Baseline, race, ethnicity, body mass 
index (BMI), and body surface area (BSA) as calculated below. Demographic characteristics will 
be summarized for the SS. 
Only the year of birth has been collected, so the age will be calculated with the documented year 
of birth, January as imputed month and 1 as imputed day of birth, at the time of informed 
consent, as follows:
Age (years) = ([Date of Informed Consent] – [Imputed Date of Birth]) / 365.25
It will be summarized as a continuous variable and as a categorical variable based on the 
following 3 categories: ≤18 years, >18 and <65 years, ≥65 years.
The BMI will be calculated using the following formula (Keys et al, 1972):
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6.2
Other Baseline characteristics
Disease duration of axSpA will be calculated as the difference between the date of Baseline visit 
and the onset date of axial spondyloarthritis (axSpA) or Ankylosing spondylitis (AS) as 
documented on the medical history pages. If the onset date of axSpA is partial, it will be imputed 
to the most recent feasible date (ie, first day of the month if only day is missing, or the first day 
of the year if day and month are missing). Disease duration of axSpA will be summarized as 
continuous variable in years, as well as categorized into <2 years and ≥2 years.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 27 of 92
Time since onset of first uveitis flare will be calculated as the difference between the date of 
Baseline visit and the onset date of first uveitis flare. If the onset date of first uveitis flare is
partial, it will be imputed to the most recent feasible date (ie, first day of the month if only day is 
missing, or the first day of the year if day and month are missing). Time since onset of first 
uveitis flare will be summarized as continuous variable in years, as well as categorized into <2 
years and ≥2 years.
Other baseline characteristics include number of subjects with IBD, number of subjects with 
psoriasis, number of subjects with at least one tender joint, and number of subjects with at least 
one swollen joint.
Data collected on childbearing potential will be listed, which includes the method of birth control 
if the subject is a female of childbearing potential, or if the subject is a fertile male. Also the 
reason why a male subject is not fertile, or why a female is not of childbearing potential is 
displayed.
Lifestyle data shows the use of alcohol, caffeinated beverages, illicit drugs, and tobacco. The 
categories will be summarized on the SS. For subjects with former or current tobacco use, the 
duration of use is collected and summarized, as well as the number of daily cigarettes, cigars, 
chewing tobacco, and pipes.
The responses to the following modified ASAS classification criteria for AS will be summarized 
for all subjects in a frequency table using the SS:
x
Back pain of ≥3 months and subject’s age at onset <45 years
x
Inflammatory back pain
x
Reactive arthritis
x
Enthesitis
x
Uveitis
x
Dactylitis
x
Psoriasis
x
Inflammatory bowel disease
x
HLA-B27
x
Elevated CRP (above upper limit of normal)
x
Sacroiliitis
If medical history terms of back pain or inflammatory back pain are missing for a subject, 
then the terms axial spondyloarthritis or Ankylosing spondylitis will used instead.
6.3
Medical history and concomitant diseases
The Medical history contains any previous or ongoing medical conditions that occurred prior to 
study entry. They will be listed for all subjects in the SS including the reported term, start date 
(month and year only), end date (month and year only) (or ongoing if applicable) and the 
information whether the procedure is related to axSpA. A glossary of all medical conditions will 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 28 of 92
also be presented including the reported term, the preferred term and the System Organ Class. 
The classification of medical history will be done according to the MedDRA coding system 
using system organ class (SOC) and preferred term (PT). These data will be summarized using 
frequency tables for subject count by classified data.
Procedure history will be displayed in a listing only, data will not be coded.
Extra-articular assessments of psoriasis, IBD, reactive arthritis and uveitis will be presented in 
listings, based on the subjects in the SS.
6.4
Prior and concomitant medications
Prior medications include any medications that started prior to the start date of study medication. 
Past medications are a subset of prior medications and include prior medications with a stop date 
before the date of first study medication administration.
Concomitant medications will be assigned to the treatment period according to whether they 
were taken at least one day in common with the study medication in that period. That is, if the 
start or end date of the concomitant medication is on or between the first study drug 
administration date and the last study drug administration date plus 14 days, or, if the 
concomitant medication starts prior to first study drug administration and ends after the last study 
drug administration date plus 14 days. 
Concomitant medications will be assigned to the follow-up period if the start date of the 
concomitant medication is after the last study drug administration date plus 14 days. 
A medication can be defined as both prior and concomitant. Where a medication start or stop 
date is (partially) missing, the medication will be considered a concomitant medication, unless 
the partial data is suggesting otherwise. Imputation of dates will follow the rules described in 
section Section 4.2 . Concomitant medications will be summarized for subjects in the SS. The 
following information will be included in the listings: reported term, dose per intake and dose 
unit, frequency, formulation, route, indication, start and stop dates (including relative study day), 
and in case of missing stop date, the information whether the intake of medication is ongoing. 
Past medication summaries will be generated for disease-modifying antirheumatic drugs 
(DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and anti-tumor necrosis factors 
(anti-TNFs) by anatomical therapeutic chemical (ATC) Anatomical Main Group (ATC Level 1),
Pharmacological Subgroup (ATC level 3), and PT).
Concomitant DMARDs and NSAIDs will be summarized by WHO-DD Anatomical Main Group 
(ATC Level 1), Pharmacological Subgroup (ATC level 3), and PT). Concomitant medications 
other than DMARDs and NSAIDs will also be summarized.
Intake of any new prohibited medication since last visit is collected and presented in a separate 
listing.
7
MEASUREMENTS OF TREATMENT COMPLIANCE
There will be 2 approaches to calculate treatment compliance. The first will utilize the number of 
administered syringes and compare them to the scheduled expected number of syringes. Two 
syringes should be administered for the loading doses (at weeks 0, 2 and 4) however only 1 
syringe should be administered at any other visit from Week 6 until Week 94/last scheduled 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 29 of 92
injection. The difference in number of syringes between the total actual used and the total
expected syringes will be summarized. In addition, a ratio of compliance will be further 
computed based on the number of actual and expected syringes. The ratio of compliance will be 
summarized as a continuous variable and categorically (<0.80, ≥0.80-≤1.0 and >1.0). The 
general formula for the compliance ratio (CR) is given as follows: 
ܥܴൌܰௌ௬௥̴௔௖௧
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where NSyr_act is the number of actual injections and NSyr_exp is the number of expected injections. 
The second approach defines compliance with study drug administration based upon comparing 
the actual day of administration with the expected day of administration. The expected day of 
administration will be based upon the Baseline date and the previous injection date. The sum of 
the absolute difference in days between the actual and expected days will be summarized. In 
addition, a ratio of compliance will be further computed based upon the actual and expected day. 
The ratio of compliance will also be summarized as a continuous variable and categorically 
(<0.80, ≥0.80-≤1.0 and >1.0). The general formula for the compliance ratio based on duration 
(CRD) is given as follows:
ܥܴܦൌܶ஽௨௥̴௦௧௨െο஼௨௠
ܶ஽௨௥̴௦௧௨
where TDur_stu is the study duration and 'Cum is the cumulative difference between actual and 
scheduled day of administration. 
Specific details of this formula are provided in Appendix 12.1 (Compliance Ratio Calculation).
The CRD ranges between 0 and 1. To calculate study duration, the date of the Week 94 visit or 
the last injection date prior to study treatment discontinuation will be compared to the Baseline 
date, as shown below:
Study Duration (days) = Week 94 visit/last injection date – Baseline date + 14
The sum will be calculated for the 11 visits from Week 0 (Baseline) to Week 84, and for all 
planned home administrations from week 6 to week 94. In case the actual day of administration 
is missing, the maximum deviation to the scheduled day will be assumed (ie, 14 days). If, for a 
scheduled day with 2 planned injections, the syringes were administered on 2 different days, the 
maximum day difference of the 2 actual dates to the scheduled date will be utilized.
8
EFFICACY ANALYSES
The efficacy analysis will be based on all subjects in the SS or FAS, as appropriate. If there is no 
missing AU flare incidence data from pre-study period, the FAS will be the same as the SS. The 
FAS will be used for analyses of the primary variable and the SS will be used for all other 
efficacy analyses. The primary efficacy analysis will additionally be repeated for the PPS.
All statistical analyses besides the primary efficacy analysis will be exploratory in nature only. 
Any p-values or confidence intervals produced in association with secondary or other analyses 
will be considered non-confirmatory.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 30 of 92
8.1
Statistical analysis of the primary efficacy variable(s)
The primary efficacy analysis will consist of a comparison of the frequency of AU flares during 
the pre-study/historical period with that observed while in the study during CZP treatment. It is 
assumed that the frequency of AU flares follows a Poisson distribution. As such, the analysis 
will be performed as a generalized estimating equations analysis for Poisson outcome that will 
take into account the possible within-subject correlation (between the retrospective and 
prospective AU flare counts). The model will contain 2 records per subject corresponding to the 
frequency of AU flares before study and during the study, offset by log-time of each of the 
reporting periods. Disease duration of axSpA will be included as a factor in the model, initially 
defined as <2 years and ≥2 years; the specific cutoffs for analysis may deviate from this based on 
the distribution seen in the data. The p-value for effect of CZP treatment on frequency of AU 
flares, along with rate ratio (CZP/historical) and 95% confidence interval, will be obtained from 
this model. The rate per 96 weeks and rate per 2 years for each study period from the model will 
also be presented.
The primary efficacy analysis hypothesis will be tested based on significance level of alpha 0.05 
and will be 2-sided. The analysis of the other secondary efficacy parameters will be supportive. 
Therefore, no alpha adjustment for secondary efficacy variables will be performed. The alpha 
adjustment related to the formal interim review of data is described in Section 4.5.
Statistical Model
Let Yij be the number of AU flare episodes for subject i in period j, where tij is the length of the 
interval. It is assumed that the responses within a subject are correlated. For the statistical model 
assumptions about the correlation structure need to be done. Assuming an exchangeable 
correlation structure means that correlation between any two responses of the ith individual is the 
same. Also we account for different interval length by adding the offset term log(tij). The mean 
of the Poisson distribution is E(Yij) = μij, and the mean response per unit time is μij/tij. The 
Poisson model using a log-link can be written as
 ߤ௜௝ൌߚ଴൅ߚଵݔଵǢ௜௝൅ߚଶݔଶǢ௜൅ ݐ௜௝
which resolves to 
ߤ௜௝ൌݐ௜௝ሺߚ଴ሻכ ൫ߚଵݔଵǢ௜௝൯כ ሺߚଶݔଶǢ௜ሻ
with the variables:
x1;ij: variable for period: 1 on-study, 0 pre-study
x2;i: variable for disease duration of axSpA: <2 years, ≥2 years.
It will be tested whether the period variable has an effect on the response variable. The null 
hypothesis H0: β1=0 of no difference between periods is tested versus the alternative hypothesis 
HA: β1≠0 of a difference between periods. This 2-sided test will be based on a significance level 
of alpha 0.05.
8.1.1
Derivations of primary efficacy variable
The primary efficacy variable is the number of distinct episodes of AU flares in the Treatment 
Period. Per protocol, a flare is considered a new episode if a gap of at least 3 months occurs 
between 2 flares. If AU flare episodes as reported by the investigator occur less than 3 months
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 31 of 92
(90 days) apart in the same eye, these will be programmatically corrected, such that a new AU 
flare within 3 months (90 days) after the end of the previous AU flare in the same eye will be 
considered as pertaining to the same AU episode. These flares will then be counted as one 
episode. Otherwise, if the time interval between 2 consecutive AU flares is greater than 3 months
(90 days), or a separate eye is affected, the AU flares will be considered as separate episodes.
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if start date 
of flare occurs within the 24 months (730 days) prior to the start of study medication. For the 
interim analysis, an episode of AU flares is considered as pre-study if the flare occurs within 48 
weeks (336 days) prior to the start of study medication. 
For the Week 96 (primary) analysis, an episode of AU flares is considered on-study, if the start 
date of flare is on or after the start date of study medication and the start date of the flare occurs 
up to and including the last visit in the treatment period, i.e. Week 96 or discontinuation visit.
Pre-study and on-study flares of the same eye will be combined if the time interval between the 
end of pre-study flare and the start of subsequent on-study flare is less than 3 months (90 days). 
The resulting flare episode will be considered as pre-study flare episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes is extended to up to 2 
years prior to Baseline, the pre-study period length for offset is 730 days for each subject, unless 
the date of first uveitis flare is within 2 years of baseline, in which case the pre-study period 
length will be from date of first uveitis flare until baseline. The on-study period length for offset 
is the time in days from start of study medication until last visit, i.e. Week 96 or discontinuation 
visit. For the interim analysis, an offset of 336 days will be used for the pre-study period or time 
since first uveitis flare if shorter than 336 days, and the time in days from start of study 
medication until week 48 visit (taken as 336 days) or early termination visit (taken as 14 days 
after the last treatment) where applicable will be used for the on-study period.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
as defined in Section 6.2, and is categorized into <2 years and ≥2 years.
8.1.2
Supportive and sensitivity analyses of the primary efficacy variable
The primary efficacy analysis will be repeated in the subgroup of subjects with at least 1 
documented AU flare within 12 months prior to Baseline.
The AU flares as reported by the investigators, without programmatically correcting for the 3
month interval between 2 flares, will be analyzed in addition to the primary efficacy variable of 
protocol-defined AU flares at least 3 months apart.
The primary analysis will be repeated using the pre-study period as 96 weeks (672 days) prior to 
start of study medication for counting flares and as the offset, instead of 24 months. The on-study 
period will be the same as that used for the primary analysis.
In addition, the analysis for the full 2 years before and after study medication will be provided. 
The pre-study period will be the 2 years (730 days) prior to start of study medication, which will 
be used for counting flares and as the offset. The on-study period will be determined for whose 
episodes of AU flares for which the start date of flare is on or after the start date of study 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 32 of 92
medication and up to and including the SFU visit or date of last administration of study 
medication + 70 days.
An analysis for the first 48 weeks will also be produced. The period for pre-study will be the 12 
months (365 days) prior to start of study medication, which will be used for counting flares and 
as the offset. An episode of AU flares will be considered on-study, if the start date of flare is on 
or after the start date of study medication and up to and including the Week 48 visit or 
discontinuation visit if prior to Week 48. The exact date of the Week 48 or discontinuation visit 
will be used for each subject. This analysis will also be repeated using 48 weeks (336 days) as 
the pre-study period for counting flares and as offset, but keeping the on-study period of 48 
weeks the same (i.e. using the exact date of the Week 48 or discontinuation visit).
The primary efficacy analysis will be repeated in the subgroup of subjects excluding those with 
any pre-study flares with completely missing end dates in the 2 years prior to baseline. Subjects 
will be excluded if any of the flares that started within the 2 years prior to baseline have 
completely missing end dates (i.e. no day, month or year)
8.2
Statistical analysis of the secondary efficacy variable(s)
Secondary and other efficacy variables will be summarized by time point including change from 
Baseline or shift from Baseline, with descriptive statistics. Arithmetic mean, SD, median, 
minimum and maximum value will be displayed for continuous variables. The secondary 
efficacy variables are assessed at Week 48 and Week 96. All efficacy analyses will be based on 
the SS or FAS as appropriate.
8.2.1
Number of AU flares per 100 patient-years
The number of AU flares per 100 patient-years in subjects with active axSpA and a history of 
AU will be calculated and the corresponding 95% confidence interval for both pre-study and on-
study periods. Similarly, the number of AU flares per 100 patient-years in subjects with active 
axSpA and at least 1 AU episode within 12 months prior Baseline, and the corresponding 95% 
confidence interval will be presented. This variable is also supportive of primary efficacy 
analysis. 
8.2.2
Ankylosing spondylitis disease activity score (ASDAS)
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2008) as shown below:
x
0.121 x 
 (BASDAI Q2 result)
x
0.058 x 
 (BASDAI Q6 result)
x
0.110 x Patient’s Global Assessment of Disease Activity (PtGADA)
x
0.073 x 
 (BASDAI Q3 result)
x
0.579 x (natural logarithm of the (CRP [mg/L] + 1))
, PtGADA, 
 are all assessed 
on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 33 of 92
If 1 component for the ASDAS is missing at a given visit, that component will be imputed by 
carrying the last observation forward, and the ASDAS will be calculated accordingly. If more 
than one component for the ASDAS is missing, ASDAS will be treated as missing.
For CRP values below the lower limit of quantification (<4mg/L), half the lower limit (2mg/L)
will be used as the imputed value. This approach will be used for summaries of CRP as well.
The nomenclature of disease activity was updated by ASAS (Machado et al, 2018). The state 
‘Moderate Disease Activity’ was replaced by ‘Low Disease Activity’ state. Disease activity 
categories based on ASDAS are as follows:
x
ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x
ASDAS-Low Disease Activity (ASDAS-LD): ASDAS >=1.3, <2.1
x
ASDAS-High Disease Activity (ASDAS-HD): ASDAS >=2.1, <=3.5
x
ASDAS-very High Disease Activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline.
Change from Baseline in ASDAS at Week 48 and Week 96 are secondary efficacy variables.
8.2.3
Bath ankylosing spondylitis disease activity index (BASDAI)
The BASDAI is the most commonly used instrument to measure the disease activity of 
ankylosing spondylitis. The BASDAI is a validated self-reported instrument which consists of 6 
horizontal Numeric Rating Scales (NRSs), each with 10 units to measure the severity of the 5 
major symptoms: 
 over the last week. To give each symptom equal weighting, 
the average of the 2 scores relating to 
 is taken. The resulting 0 to 50 sum score 
is divided by 5 to give a final BASDAI score between 0 and 10, with lower scores indicating 
lower disease activity. The BASDAI questions can be found in appendix 16.4 of the clinical 
study protocol.
If 1 of the 2 
 measurements (ie, questions: 
 
 and 
 
is missing, the other one will be used for the 
 calculation. The same imputation is also applied for the calculation of the 
ASAS inflammation component, which is calculated as the average of the 2 
measurements.
If 1 major symptom of the BASDAI is missing, the sum score of the remaining symptoms will be 
divided by the number of symptoms assessed. If more than 1 major symptom is missing, the sum 
score will be set to missing.
A response variable called BASDAI50 is defined as an improvement of at least 50% in the 
BASDAI compared to Baseline.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 34 of 92
Change from Baseline in BASDAI at Week 48 and Week 96 are secondary efficacy endpoints.
8.2.4
ASAS20, ASAS40, and ASAS PR
The ASAS20 response 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 (Anderson, 2001):
x
Patient’s Global Assessment of Disease Activity;
x
Pain assessment (the total spinal pain NRS score);
x
Function (represented by the Bath Ankylosing Spondylitis Functional Index (BASFI));
x
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(BASDAI) questions [Q] 5 and 6) 
)
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 improvement 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 partial remission (PR) response is defined as a score of ≤2 units on a 0 to 10 unit
scale in all 4 domains.
8.2.5
Physician’s global assessment of disease activity (PhGADA)
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 visual analog scale where 0 is “very 
good, asymptomatic and no limitation of normal activities” and 100 is “very poor, very severe 
symptoms that are intolerable, and the inability to carry out all normal activities.” The data 
including the change from baseline at Week 48 and Week 96 will be summarized as secondary 
endpoints.
8.2.6
Swollen and tender joint counts
The following 44 joints are to be examined for swelling and tenderness by the 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. 
x
Upper body (4) – bilateral sternoclavicular and acromioclavicular joints.
x
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.
x
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, 
ankylosed, and missing joints are excluded from swelling and tenderness assessments.
Each joint is scored for tenderness as follows:
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 35 of 92
0 = None (not tender)
1 = Positive (tender)
Each joint is scored for swelling as follows:
0 = None
1 = Detectable
Tender joint counts (TJC) and swollen joint counts (SJC) are calculated as the sum of tender and 
swollen joints, respectively, among the 44 joints. Both TJC and SJC range from 0 to 44.
If there are missing observations for tender or swollen joints then the remaining observations will 
be assessed and weighted by dividing by number of non-missing and then multiplying by 44 for 
the joint count. If a joint is not evaluable at Baseline, then that joint is set to missing throughout 
the study. If data for more than 50% of the joints are missing at the time of a given assessment, 
then no imputation will be done and the total TJC or SJC will be set to missing for that visit.
TJC summaries will be based only on those subjects with at least one tender joint at Baseline. 
Similarly, SJC tables will be based only on those subjects with at least one swollen joint at 
Baseline.
The data including the change from baseline at Week 48 and Week 96 will be summarized as 
secondary endpoints.
8.2.7
Patient’s global assessment of disease activity (PtGADA)
For the PtGADA questionnaire, 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, 2015). 
The data including the change from baseline at Week 48 and Week 96 will be summarized as 
secondary endpoints.
8.2.8
Total and nocturnal spinal pain
The questionnaire for pain in the spine due to AS consists of 2 questions (ie, “How much pain of 
your spine due to spondylitis do you have?”; and “How much pain of your spine due to 
spondylitis do you have at night?”) (van der Heijde et al, 2005). Total and nocturnal spinal pain 
will be recorded based on a NRS ranging from 0 to 10, where 0 represents no pain and 10 
represents most severe pain. Usually, a 10% difference (ie, a 1 point difference on a NRS 
ranging from 0 to 10) is considered the minimal clinically important difference used to interpret 
scores (Dworkin et al, 2008). The total spinal pain data including the change from baseline at 
Week 48 and Week 96 will be summarized as secondary endpoints.
8.2.9
Bath ankylosing spondylitis functional index (BASFI)
The BASFI contains 10 questions. The first 8 questions 
. The final 2 questions 
. An NRS ranging from 0 to 10 is used to 
answer the questions on the test. The BASFI questions can be found in appendix 16.7 of the 
clinical study protocol.
The mean of the 10 scales gives the BASFI score, which is a value between 0 and 10.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 36 of 92
In case of missing answers to 1 or 2 of the single items within the BASFI questionnaire, the 
BASFI score will be calculated by imputing missing items with the mean of the completed items. 
Then, the BASFI score will be calculated as described above. If more than 2 of the items are 
missing, the BASFI score will be left missing.
Change from Baseline in BASFI at Week 48 and Week 96 are secondary efficacy endpoints.
8.3
Analysis of other efficacy variables
All other efficacy endpoints with exception of flare duration and severity will be tabulated at all 
time points acc to assessment schedule.
8.3.1
Flare assessments
For each subject in FAS, the total duration and the maximum severity of pre-study and on-study 
AU flares will be determined and summarized. The duration of an episode of AU flare (TDur_Fl) is
calculated as follows: 
ܶ஽௨௥̴ி௟ൌܦܽݐ݁ா௡ௗ̴ி௟െܦܽݐ݁ௌ௧௔௥௧ಷ೗൅ͳ
with DateEnd_Fl and DateStart_FL the end date and start date of flare, respectively. The duration of 
pre-study and on-study periods is defined in Section 4.2.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 days 
prior to Baseline until Baseline. The on-study period for the interim analysis is starting from 
Baseline until week 48, i.e. until study day 336. 
For the final analysis, the pre-study period is starting 24 months prior to Baseline, i.e. 730 days 
prior to Baseline until Baseline. The on-study period for the final analysis is starting from
Baseline until week 96, i.e. until the date of the Week 96 or discontinuation visit.
The highest grade (severity) of uveitis flare across all flares per subject will be summarized. The 
highest grade (severity) noted during an episode of uveitis will be graded as follows: Grade 
0=None; Grade 1+=Faint; Grade 2+=Moderate, iris and lens details clear; Grade3+=Marked, iris 
and lens details hazy; Grade4+=Intense, fibrin or plastic aqueous; ND=Not done or not assessed; 
UNK=Unknown
8.3.2
Extra-articular assessments
Extra-articular assessments (eg, number of IBD exacerbations and number of psoriasis 
exacerbations) are to be performed at Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, and 
at Completion at Week 96/WD Visit. At each visit, the number of episodes since the last visit 
and the number of days with IBD/psoriasis are collected. Episodes are considered equivalent to 
exacerbations. These data will be summarized using summary statistics for continuous variables.
8.3.3
Ankylosing spondylitis quality of life (ASQoL)
The ASQoL consists of 18 items, each with a score of 0 = no or 1 = yes, so that the sum score 
ranges from 0 to 18, with higher scores indicating worse quality of life. The questions of ASQoL 
can be found in appendix 16.8 of the clinical study protocol.
If 6 or fewer items are missing, the missing responses will be imputed with the mean of the 
available responses from that visit to calculate a total score. If more than 6 items are missing, the 
total score will be left missing.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 37 of 92
The ASQoL total score will be tabulated by visit.
8.3.4
ASAS Health Index (ASAS HI) Questionnaire
The ASAS HI has been developed under the auspices of ASAS to assess health in subjects with 
all forms of SpA. The questionnaire contains 17 items measuring “functioning, disability and 
health”, these items are given in appendix 16.9 of the clinical study protocol.
Each statement on the ASAS HI is given a score of 1=I agree OR 0=I do not agree. All item 
scores are summed up to give a total score that ranges from 0 (good functioning) to 17 (poor 
functioning).
It is to be noted that items 7 and 8 are not applicable for all subjects. For those subjects who 
ticked the response “not applicable,” the sum score is analyzed based on n=16 or n=15, 
respectively.
Missing data:
A total score can be analyzed if no more than 20% of the data are missing. The total score is 
calculated as follows for respondents with 1 to a maximum of 3 missing responses:
Sumscore = [ x / (17-m)] ·17, where x=Item summation score and m=Number of missing items.
Cases with more than 3 missing responses cannot be allocated a total score. The ASAS HI 
questionnaire assessments will be listed, and the total score will be tabulated by visit.
8.3.5
Short-Form 36-Item Health Survey (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. The 
items of SF-36 can be found in appendix 16.10 of the clinical study protocol.
For the calculation of the SF-36 domain scores and the component summaries PCS and MCS, the 
scoring software QualityMetric Health Outcomes™Scoring Software 4.5 will be used. The norm-
based scores (based on the US general population for 2009) will be utilized for analysis.
9
PHARMACOKINETICS AND PHARMACODYNAMICS 
9.1
Pharmacokinetics
Not applicable.
9.2
Pharmacodynamics
Not applicable.
10
SAFETY ANALYSES
All safety analyses will be based on the SS.
10.1
Extent of exposure
The number of doses received will be summarized with continuous statistics for the SS.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
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Duration of exposure to study medication will be calculated as:
int
d
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Dur
First
Last
Exp


 
where dint represents the dosing interval of 14 days.
The cumulative duration of exposure will be summarized for subjects exposed for at least one 
day, ≥183 days, ≥365 days, ≥548 days, ≥730 days. 
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calculated as:


2
1
*
5 t
date
date
T
First
Last
Risk


 
where t1/2 is 14 days.
If there is a change of treatment or the last clinical contact occurs prior to completion of the 
follow-up period, the date of last clinical contact per subject is defined as the maximum of [last 
visit date including safety follow-up visits, last imputed AE start date, last date of termination or 
completion, last date of study drug administration, death date] or the clinical cutoff date for 
ongoing studies if earlier than this maximum date).
In cases where the date of last clinical contact (LastCC) occurs prior to completion of this 
follow-up period, subject time at risk (in days) will be calculated as:
1


 
First
LastCC
Risk
date
date
T
Subject years at risk is the sum of all relevant subject time at risk (in days) divided by 365.25.
The study medication duration will be listed together with the dates of first and last study 
medication administration.
10.2
Adverse events
Adverse events with start date prior to first administration of study medication are defined as 
pre-treatment AEs. No summaries of these events will be produced although they will be 
included in listings. 
Adverse events that started more than 70 days after the last administration of study medication 
are defined as post-treatment AEs. Such events will not be included in tabulated summaries, but
will be listed.
Treatment emergent AEs are all AEs starting on or after the date of first study medication and up 
to 70 days after the last (most recent) dose of study medication. AEs occurring more than 70 
days after the last (most recent) dose will not be considered treatment emergent, regardless of 
whether this occurs during the safety follow-up period, or after a treatment gap of more than 70 
days.
If a start date is missing, then the AE will be considered a treatment emergent adverse event 
(TEAE).  Duration should not be calculated if there is missing stop date information. 
If the intensity of an adverse event is unknown, it is considered as severe. If the relationship to 
study drug is missing, it is considered as related.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
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Page 39 of 92
Tables showing TEAEs, serious TEAEs, non-serious TEAEs, TEAEs leading to discontinuation 
of study drug, TEAEs by maximum intensity, TEAEs by relationship, serious TEAEs by 
relationship, fatal TEAEs by relationship, TEAEs including subject numbers will be provided on 
the SS.
Additionally, more detailed summaries of TEAEs will be presented, which include the exposure 
adjusted incidence rate (EAIR) with associated 95% confidence interval, and the exposure 
adjusted event rate (EAER).
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the exposure
and will be scaled to 100 patient-years:
¦
 
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N
i
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Exp
T
n
EAIR
1
,
100
If a subject has multiple events, the time of exposure is calculated to the first occurrence of the 
AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the relationship 
between the Poisson and the Chi-square distribution (Ulm, 1990):
2
2
2
,
2
D
F n
LCL  


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2
2
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where n is the number of subjects with a specific AE for the incidence rate of interest and is the 
basis for the number of the degrees of freedom for the chi-square quantile for the upper tail 
probability χ2.
The EAER will be the number of AEs including repeat occurrences in individual subjects
divided by the total time at risk scaled to 100 patient-years and calculated using:
¦
 
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N
i
i
Risk
AE
T
N
EAER
1
,
100
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Where an AE start date is (partially) missing, the AE will be considered TE if possible. 
Imputation rules provided in Section 4.2 are based on the assumption that if the start date is 
incomplete, either day only is missing, or day and months are missing, or date is completely
missing. Although the algorithms for treatment-emergence depend on the onset date, imputation 
rules are provided for resolution date as well, as these may be needed for certain statistical 
analyses, such as an analyses of AE prevalence or AE duration.
Listings based on SS for all AEs will be provided. A glossary for the reported terms will also be
generated utilizing SOC, HLT, and PT.
Anticipated SAEs, as described in Section 10.5 of the clinical study protocol, will not be 
summarized either by any additional tables or listings, as they are included in the standard AE 
summaries.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 40 of 92
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:
x
Opportunistic infections
x
Malignant or unspecified tumors
x
Malignant tumors
x
Serious cardiovascular events
x
Demyelinating-like disorders
x
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x
Serious bleeding events
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:
x
Serious infections 
x
Congestive heart failure
x
Lupus and lupus-like illness
x
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following notes to AEs of interest in the clinical study protocol are given for reporting 
purposes only, and therefore will not be summarized separately: A confirmed LTBI must be 
reported as an AE of interest. Confirmed active TB is an AE of interest. In the event that an 
active TB occurrence meets the protocol’s SAE criteria, it is also an SAE. Potential Hy’s Law, 
defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality is also considered an AE of interest.
The following events are not officially considered to be AEs of interest but are nonetheless 
considered to be interesting enough to be summarized in stand-alone tables:  1) Hepatic events 
and 2) Hypersensitivity reactions and anaphylactic reactions.
The approach for summarizing AEs of interest is detailed in the 
UCB AE of interest program specifications for Cimzia from 18 June 2018.
Data collected on hospitalization will be presented in a listing.
10.3
Clinical laboratory evaluations
Hematology, biochemistry, and urinalysis samples will be taken at Screening, Baseline, 
Weeks 2, 4, 12, 24, 36, 48, 60, 72, 84, and 96/WD Visit. Testing for HBs-Ag, HBc-Ab, HBs-Ab,
HCV-Ab, HIV, and HLA-B27 (if not yet known) will be performed at Screening.
The changes from Baseline in laboratory evaluations will be analyzed over time in the SS for 
observed cases. Shift tables concerning the normal range at each post-baseline visit, will also be 
produced for each hematology and biochemistry laboratory variable. The shifts will be 
categorized using L, N, H, missing, and total.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 41 of 92
Markedly abnormal laboratory values
The number of subjects with any markedly abnormal hematology or biochemistry value will be 
tabulated. Values fulfilling the criteria below will be classified as markedly abnormal high (MH) 
or markedly abnormal low (ML). If no lower (upper) limit is given, the classification ML (MH) 
is not applicable.
x
Hemoglobin < lower limit normal (LLN) and decrease from Baseline >2g/dL
x
Hemoglobin <8g/dL
x
White blood cells <2000/μL
x
Lymphocyte count <1000/μL
x
Neutrophil count <1000/μL
x
Platelet count <50000/μL
x
ALT >3x upper limit normal (ULN)
x
AST >3x ULN
x
ALP >3x ULN
x
Bilirubin ≥2x ULN
x
Creatinine >1.8x ULN
x
Calcium >12.5mg/dL
x
Calcium <7mg/dL
x
CK >4x ULN
x
Glucose >250mg/dL
x
Glucose <40mg/dL
x
Potassium >6.4mmol/L
x
Potassium <3mmol/L
x
Sodium <125mmol/L
x
Uric acid ≥3x ULN
The number of subjects meeting the criteria for Hy’s Law is of particular importance. The 
criteria are as follows:
x
>=2 x ULN elevation of Bilirubin and 3 x ULN elevation of either ALT or AST
In order to meet the above criteria, a subject must experience the elevation in bilirubin and ALT 
or AST at the same visit. For example, a subject who experiences a >=2 x ULN elevation of 
bilirubin at one visit and a 3 x ULN elevation in ALT (or AST) at a subsequent visit has not 
fulfilled the Hy’s law criteria. 
If a repeat sample is taken, the repeated sample data will be used when possible. If the value of a 
variable collected at the scheduled visit is missing and an additional sample associated with this 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
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Page 42 of 92
visit is taken before the next scheduled visit, the missing value will be replaced by this value. 
Early Withdrawal Visits will be assigned to what would have been the next scheduled visit. In 
the Urinalysis, microscopy (WBC, RBC, casts, crystals, and bacteria) will be performed only 
when there are abnormalities on the dipstick. This data will be listed and not presented in tables.
10.4
Vital signs, physical findings, and other observations related to 
safety
10.4.1
Vital signs
The changes from Baseline in vital signs will be analyzed over time in the SS for observed cases. 
In addition, the last value (end of treatment) during treatment will be analyzed. End of treatment 
will be defined as last visit not including the Follow-up visit. Early Withdrawal Visits will be 
assigned to what would have been the next scheduled visit. The following vital signs 
measurements will be assessed:
x
Pulse rate (bpm)
x
Systolic blood pressure (mmHg)
x
Diastolic blood pressure (mmHg)
x
Body temperature (ºC)
Additionally, body weight (kg) will also be presented together with vital signs.
10.4.2
Pregnancy testing
Pregnancy testing must be carried out for women of childbearing potential and will consist of 
serum testing at Screening, and urine dipstick testing at Baseline, Week 96/WD Visit, and FU 
Visit. No tables will be generated and data listed only.
10.4.3
Physical assessments
A physical examination will be performed at Screening, Baseline, Weeks 2, 4, 12, 24, 36, 48, 60, 
72, 84, 96/WD Visit, and at the FU Visit. Physical examination findings will be recorded in the 
eCRF only at Screening. Physical examination data will be listed only.
10.4.4
MRI assessments
Magnetic resonance imaging of the SIJs will be performed at the Screening Visit only. An MRI 
performed ≤3 months prior to the Baseline Visit may be used as the Baseline. The data will be 
presented in a listing only.
10.4.5
Tuberculosis assessments
The interferon-gamma release assay (IGRA) test will be done by the central laboratory. The test 
results will be reported as positive, negative, or indeterminate and must be reviewed by an 
experienced TB specialist, radiologist, or a pulmonologist. The test result data, the data about 
history of latent tuberculosis, as well as the TB questionnaire result data, including the 2 
questions 
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be presented in listings.
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
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10.4.6
Chest x-ray
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. Additional chest x-ray or other imaging test should be performed when 
positive signs and symptoms indicate pulmonary infection, including potential TB infection, or 
when close exposure to persons with TB is documented. The data collected on chest x-ray will
not be tabulated, but presented in a listing.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof. 


UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
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Page 44 of 92
11
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Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in 
chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105-21.
Garwood F. Fiducial limits for the Poisson distribution. Biometrika. 1936;28:437-42.
Haybittle JL. Repeated assessments of results in clinical trials of cancer treatment. Brit. J. 
Radiol. 1971. 44 (526):793-7.
Hu K. Sample Size Estimation for Trials of Recurrent Events. Amgen Inc. 2008. 1-8.
Keys A; Fidanza F; Karvonen M; Kimura N; Taylor H. Indices of relative weight and obesity. 
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Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an 
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Rheum Dis. 2009; 68(1):18-24.
Machado PM, Landewé R, Heijde Dv, et al. Ann Rheum Dis Epub ahead of print: 16 Feb 2018.
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Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987 Oct22; 
317(17):1098 (letter).
Signorini DF. Sample size for Poisson regression. Biometrika. 1991. 78:446-50.
Ulm K. A simple method to calculate the confidence interval of a standardized mortality ratio. 
American Journal of Epidemiology 1990;131(2):373-375.
van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of 
scoring methods. Ann Rheum Dis. 2005;64;ii61-ii64.
van Tubergen A, Black PM, Coteur G. Are patient-reported outcome instruments for ankylosing 
spondylitis fit for purpose for the axial spondyloarthritis patient? A Qualitative and Psychometric 
Analysis. Rheumatology. 2015; 54(10):1842-51.
Ware JE, Kosinski M, Keller SD. SF-36 Physical and Mental Health Summary scales: a user’s 
manual. 1994. Maruish, M. E. (Ed.) 2011.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 45 of 92
12
APPENDICES
12.1
APPENDIX 1: Compliance Ratio Calculation
The general formula for treatment compliance is given as follows:
ܥܴൌܶ஽௨௥̴௦௧௨ିο஼௨௠
ܶ஽௨௥̴௦௧௨
where TDur_stu is the study duration and 'Cum is the cumulative difference between actual and 
scheduled day of administration. The CRD ranges between 0 and 1. 
There are 2 methods to determine the CR. CR (1) is based upon scheduled days which reference 
the Baseline visits. CR (2) is based upon scheduled days which reference the previous dosing 
administration date. CR (1) and CR (2) each will be computed separately. The definition of study 
duration and cumulative difference varies for the 2 calculations. In all cases, if the subject was 
randomized, but study drug was never administered then the CR is equal to 0. The CR is limited 
to a range of 0 to 1. Therefore, if for any reason a negative value is computed, the CR must be set 
to 0. Specific details for each calculation follow.
CR(1):
ܶ஽௨௥̴௦௧௨ൌܦܽݐ݁௅௔௦௧െܦܽݐ݁஻௅
ο஼௨௠ൌσ ȁሺܣܦ௜െܵܦ௜ȁ
௜
where i=Week 0, 2, 4, 6,  … , XX
ADi = Actual day of administration, for Week i=0 to XX by 2
SDi = (i/2) x 14, 
for Week i=0 to XX by 2
Note: XX represents the last completed visit in which study drug should have been administered. 
If subject is still in the study but ADi is missing, then ABS[ADi – SDi]=14 for the missed Visit i.
CR(2):
ܶ஽௨௥̴௦௧௨ൌܦܽݐ݁௅௔௦௧െܦܽݐ݁஻௅
ο஼௨௠ൌσ ȁሺܣܦ௜െܵܦ௜ȁ
௜
where i= Week 0, 2, 4, 6,  … , XX
ADi = Actual day of administration, for Week i=0 to XX by 2
SDi = {0,
for Week i=0
}
{14 + ADi-2,
for Week i=2 to XX by 2 }
Note: XX represents the last completed visit in which study drug should have been administered. 
If subject is still in the study but ADi is missing, then ABS(ADi – SDi)=14 for the missed Visit i.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 46 of 92
Example
Week
Scheduled
day (1)
Scheduled
day (2)
Actual day
ABS Diff (1)
ABS Diff (2)
0
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66/84 =0.79
65/84 =0.77
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 47 of 92
13
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) (IF APPLICABLE)
13.1
AMENDMENT 1
Rationale for the amendment
This SAP was amended after the Data Evaluation Meeting, in order to include the handling of 
AU flares if the time interval between 2 subsequent flares is less than 3 months. The 
corresponding derivations for the analysis of the primary efficacy variable, including imputation 
of start and end dates of flares, have been added. In addition, the interim analysis will include 
data up to Week 48 only. And according to the most recent AE of interest guidance, separate
tables for demyelinating disorders and congestive heart failures were included.
Modifications and changes
Changes in section 4.2
Following has been added at the end of section 4.2:
Efficacy variables
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
Pre-study period (12 months prior to Baseline, i.e. 365 days prior to Baseline, until Baseline):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare, and the 
end date is clearly greater than end date of previous flare, then impute with the end date 
of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare, then use the latest date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare, then impute with the end date 
of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare, then use the latest date of both for imputation.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 48 of 92
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within 12 months prior to treatment start. Then the maximum
(latest) of start date of pre-study period and end date of previous flare will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

Month and year are the same as month and year of the start date of subsequent pre-study 
flare before Baseline, then impute with the start date of subsequent pre-study flare. 

In the case that month and year of the end date of pre-study period is the same month and 
year of the start date of subsequent pre-study flare, then use the earliest date of both for 
imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 

Year is the same as year of the start date of subsequent pre-study flare, then impute with
the start date of subsequent pre-study flare. 

In the case that year of the end date of pre-study period is the same year of the start date 
of subsequent pre-study flare, then use the earliest date of both for imputation.
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred within 12 months prior to treatment start. Then the minimum
(earliest) of end date of pre-study period and start date of subsequent pre-study flare will be 
considered.
On-study period (Baseline until end of treatment):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of study medication, then 
impute with the start date of study medication. 

Month and year are the same as month and year of the end date of previous on-study 
flare, and the end date is clearly greater than end date of previous on-study flare, then 
impute with the end date of previous on-study flare. 

In the case that month and year of the start date of study medication is the same month 
and year of the end date of previous on-study flare, then use the latest date of both for 
imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 49 of 92

Year is the same as year of the start date of study medication, then impute with the start 
date of study medication. 

Year is the same as year of the end date of previous on-study flare, then impute with the 
end date of previous on-study flare. 

In the case that year of the start date of study medication is the same year of the end date 
of previous on-study flare, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred after treatment start during the on-study period. Then the 
maximum (latest) of start date of study medication and end date of previous on-study flare 
will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of on-study period, then 
impute with the end date of on-study period. 

Month and year are the same as month and year of the start date of subsequent on-study 
flare, then impute with the start date of subsequent on-study flare.

In the case that month and year of the end date of on-study period is the same month and 
year of the start date of subsequent on-study flare, then use the earliest date of both for 
imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of on-study period, then impute with the end date 
of on-study period. 

Year is the same as year of the start date of subsequent on-study flare, then impute with
the start date of subsequent on-study flare. 

In the case that year of the end date of on-study period is the same year of the start date of 
subsequent on-study flare, then use the earliest date of both for imputation.
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred after treatment start during the on-study period. Then the 
minimum (earliest) of end date of on-study period and start date of subsequent on-study flare 
will be considered.
Changes in section 4.3 (third paragraph)
An interim analysis is planned to be conducted after the last subject has completed the Week 48 
assessment. That is when each treated subject has completed the Week 48 Visit, or withdrawn 
prematurely. All data collected until the database cut-off date will be included. With this interim 
analysis, first study results will be available already about one year before the final analysis of 
the study. There is no intention to stop the study early for efficacy or for futility. The interim 
summaries and listings will be based on the same shells as for the final analysis, unless otherwise 
stated. The interim listings will include all data collected so far, and also display data after Week 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 50 of 92
48 if available. The summary tables presenting results by visit will only consider results up to 
Week 48 Visit for the interim analysis. Summary tables of results not provided by visit, e.g. 
adverse events, concomitant medication, will consist of all the data collected so far at the interim 
cut-off. All AU flares will be counted for a subject, irrespective of whether a subject has only 48 
weeks of data or already more weeks of data collected.
Has been changed to:
An interim analysis is planned to be conducted after the last subject has completed the Week 48 
assessment. That is when each treated subject has completed the Week 48 Visit, or withdrawn 
prematurely. All data collected until the database cut-off date will be included. With this interim 
analysis, first study results will be available already about one year before the final analysis of 
the study. There is no intention to stop the study early for efficacy or for futility. The interim 
summaries and listings will be based on the same shells as for the final analysis, unless otherwise 
stated. The interim listings will include all data collected up to Week 48. The summary tables
presenting results by visit will only consider results up to Week 48 Visit for the interim analysis.
Summary tables of results not provided by visit, e.g. adverse events, concomitant medication, 
will not include events or medication that started after the Week 48 Visit. Data collected 
after Week 48 will not be presented in the interim analysis.
Changes in section 6.2 (second paragraph)
Time since onset of first uveitis flare will be calculated as the difference between the date of 
Baseline visit and the onset date of first uveitis flare. If the onset date of first uveitis flare is 
partial, it will be imputed to the most recent feasible date (ie, last day of the month if only day is 
missing, or the last day of the year if day and month are missing). Time since onset of first 
uveitis flare will be summarized as continuous variable in days, as well as categorized into <2 
years and ≥2 years.
Has been changed to:
Time since onset of first uveitis flare will be calculated as the difference between the date of 
Baseline visit and the onset date of first uveitis flare. If the onset date of first uveitis flare is 
partial, it will be imputed to the first feasible date (ie, first day of the month if only day is 
missing, or the first day of the year if day and month are missing). Time since onset of first 
uveitis flare will be summarized as continuous variable in days, as well as categorized into <2 
years and ≥2 years.
Changes in section 8.1.1
The primary efficacy variable is the number of distinct episodes of AU flares in the Treatment 
Period. Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is 
considered as pre-study, if the start date of flare is before the start date of study medication. An 
episode of AU flares is considered on-study, if the start date of flare is on or after the start date of 
study medication.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes starts 12 months prior to 
Baseline, the pre-study period length for offset is 365 days for each subject. The on-study period 
length for offset is the time in days from start of study medication until last visit.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 51 of 92
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
from the start date of first AU flare episode until the Baseline visit date, and is categorized into 
<2 years and ≥2 years.
Has been changed to:
The primary efficacy variable is the number of distinct episodes of AU flares in the Treatment 
Period. Per protocol, a flare is considered a new episode if a gap of at least 3 months occurs 
between 2 flares. If AU flare episodes as reported by the investigator occur less than 3 
months (90 days) apart in the same eye, these will programmatically corrected, such that a 
new AU flare within 3 months (90 days) after the end of the previous AU flare in the same 
eye will be considered as pertaining to the same AU episode. These flares will then be 
counted as one episode. Otherwise, if the time interval between 2 consecutive AU flares is 
greater than 3 months (90 days), or a separate eye is affected, the AU flares will be 
considered as separate episodes.
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if the flare 
occurs within the 12 months (365 days) prior to the start of study medication. An episode of 
AU flares is considered on-study, if the start date of flare is on or after the start date of study 
medication. Pre-study and on-study flares of the same eye will be combined if the time 
interval between the end of pre-study flare and the start of subsequent on-study flare is less 
than 3 months (90 days). The resulting flare episode will be considered as pre-study flare 
episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes starts 12 months prior to 
Baseline, the pre-study period length for offset is 365 days for each subject. The on-study period 
length for offset is the time in days from start of study medication until last visit.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
from the start date of first AU flare episode until the Baseline visit date, and is categorized into 
<2 years and ≥2 years.
Changes in section 8.1.2
The primary efficacy analysis will be repeated in the subgroup of subjects with at least 1 
documented AU flare within 12 months prior to Baseline.
The AU flare rate (event rate) per 100 patient-years of exposure, both before and during the 
study will be calculated. The corresponding rate ratio along with 95% confidence interval 
(Garwood, 1936) will be presented as a key supportive analysis to the primary efficacy analysis 
results (see Section 8.2.1 ).
Has been changed to:
The primary efficacy analysis will be repeated in the subgroup of subjects with at least 1 
documented AU flare within 12 months prior to Baseline.
The AU flares as reported by the investigators, without programmatically correcting for 
the 3 month interval between 2 flares, will be analyzed in addition to the primary efficacy 
variable of protocol-defined AU flares at least 3 months apart.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 52 of 92
The AU flare rate (event rate) per 100 patient-years of exposure, both before and during the 
study will be calculated. The corresponding rate ratio along with 95% confidence interval 
(Garwood, 1936) will be presented as a key supportive analysis to the primary efficacy analysis 
results (see Section 8.2.1 ).
Changes in section 8.2.2 (last paragraph)
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline
Change from Baseline in ASDAS at Week 48 and Week 96 are secondary efficacy variables.
Has been changed to:
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS- Clinical Improvement (ASDAS-CI): ASDAS reduction (improvement) of >0 
relative to Baseline
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline or has the lowest score possible post-baseline (i.e. when CRP<LLOQ 
and all other components are 0, then the minimum ASDAS score is 0.636 to 3 decimal 
places).
Change from Baseline in ASDAS at Week 48 and Week 96 are secondary efficacy variables.
Changes in section 10.2
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:
x
Opportunistic infections
x
Malignant and unspecified tumors
x
Malignant tumors
x
Serious cardiovascular events
x
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x
Serious bleeding events
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:
x
Serious infections 
x
Demyelinating-like disorders
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 53 of 92
x
Congestive heart failure
x
Lupus and lupus-like illness
x
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following notes to AEs of interest in the clinical study protocol are given for reporting 
purposes only, and therefore will not be summarized separately: A confirmed LTBI must be 
reported as an AE of interest. Confirmed active TB is an AE of interest. In the event that an 
active TB occurrence meets the protocol’s SAE criteria, it is also an SAE. Potential Hy’s Law, 
defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase with coexisting
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality.
Has been changed to:
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:
x
Opportunistic infections
x
Malignant and unspecified tumors
x
Malignant tumors
x
Serious cardiovascular events
x
Demyelinating-like disorders
x
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x
Serious bleeding events
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:
x
Serious infections 
x
Congestive heart failure
x
Lupus and lupus-like illness
x
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following notes to AEs of interest in the clinical study protocol are given for reporting 
purposes only, and therefore will not be summarized separately: A confirmed LTBI must be 
reported as an AE of interest. Confirmed active TB is an AE of interest. In the event that an 
active TB occurrence meets the protocol’s SAE criteria, it is also an SAE. Potential Hy’s Law, 
defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality is also considered an AE of interest.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 54 of 92
13.2
AMENDMENT 2
Rationale for the amendment
This SAP was modified to implement decisions from the second Data Evaluation Meeting. This 
includes the updated definition of Baseline to consider also assessments that were done shortly 
after the first study medication administration but still on the same day of first study medication 
administration. In addition, the SAP was revised to include collection of ASAS classification 
criteria as part of the medical history following the extension of the pre-study period for AU flare 
collection.
Modifications and changes
Changes in section 3.3
Unless otherwise specified, the last valid measurement before study medication administration 
will be utilized as Baseline value. For almost all variables, this will be the assessment made at 
the Baseline visit. However, for some variables, assessments may be scheduled for Screening 
only and not for Baseline. In this case the screening value will be utilized as baseline value. If a 
baseline measurement is missing, and a screening value available, the screening value will be 
utilized as Baseline instead. If a Baseline visit measurement is missing, and a Screening visit 
measurement is available, the Screening value will be utilized as Baseline. If a scheduled 
Baseline assessment is taken on the same day as first administration of study medication and no 
time is collected, it will be assumed to have been taken prior to study medication.
Has been changed to:
Unless otherwise specified, the last valid measurement before study medication administration 
will be utilized as Baseline value. For almost all variables, this will be the assessment made at 
the Baseline visit. However, for some variables, assessments may be scheduled for Screening 
only and not for Baseline. In this case the screening value will be utilized as baseline value. If a 
baseline measurement is missing, and a screening value available, the screening value will be 
utilized as Baseline instead. If a Baseline visit measurement is missing, and a Screening visit 
measurement is available, the Screening value will be utilized as Baseline. If a scheduled 
Baseline assessment is taken on the same day as first administration of study medication, it 
will be used as Baseline, irrespective of the time of the assessment relative to the first 
administration of study medication.
Changes in section 3.5.3
The FAS will consist of all subjects in the SS with non-missing Baseline value for the primary 
efficacy variable, i.e. AU flare incidence data from pre-study period.
In the unlikely event that the FAS differs from the SS, the efficacy analysis will be conducted 
using the FAS instead of the SS.
Has been changed to:
The FAS will consist of all subjects in the SS with non-missing Baseline value for the primary 
efficacy variable, i.e. AU flare incidence data from pre-study period.
If the FAS differs from the SS, the efficacy analysis will be conducted using the FAS instead of 
the SS.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 55 of 92
Changes in section 4.2 (Efficacy variables)
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
Pre-study period (12 months prior to Baseline, i.e. 365 days prior to Baseline, until Baseline):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare, and the 
end date is clearly greater than end date of previous flare, then impute with the end date 
of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare, then use the latest date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare, then impute with the end date 
of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within 12 months prior to treatment start. Then the maximum 
(latest) of start date of pre-study period and end date of previous flare will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

Month and year are the same as month and year of the start date of subsequent pre-study 
flare before Baseline, then impute with the start date of subsequent pre-study flare. 

In the case that month and year of the end date of pre-study period is the same month and 
year of the start date of subsequent pre-study flare, then use the earliest date of both for 
imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 56 of 92

Year is the same as year of the start date of subsequent pre-study flare, then impute with 
the start date of subsequent pre-study flare. 

In the case that year of the end date of pre-study period is the same year of the start date 
of subsequent pre-study flare, then use the earliest date of both for imputation.
Completely missing end dates of flares will only be imputed if it is clear based on the start date 
that the flare occurred within 12 months prior to treatment start. Then the minimum (earliest) of 
end date of pre-study period and start date of subsequent pre-study flare will be considered.
Has been changed to:
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 
days prior to Baseline until Baseline. The on-study period for the interim analysis is 
starting from Baseline until week 48, i.e. until study day 336.
For the final analysis, the pre-study period is starting 96 weeks prior to Baseline, i.e. 672 
days prior to Baseline until Baseline. The on-study period for the final analysis is starting 
from Baseline until week 96, i.e. until study day 672. In addition, the period definition used 
for interim with period length of 48 weeks will be repeated for the final analysis.
Pre-study period (48 vs 96 weeks prior to Baseline, i.e. 336 vs 672 days prior to Baseline, until 
Baseline for interim vs final analysis):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare, and the 
end date is clearly greater than end date of previous flare, then impute with the end date 
of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare, then use the latest date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare, then impute with the end date 
of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare, then use the latest date of both for imputation.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 57 of 92
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within the pre-study period. Then the maximum (latest) of start 
date of pre-study period and end date of previous flare will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

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flare before Baseline, then impute with the start date of subsequent pre-study flare. 

In the case that month and year of the end date of pre-study period is the same month and 
year of the start date of subsequent pre-study flare, then use the earliest date of both for 
imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 

Year is the same as year of the start date of subsequent pre-study flare, then impute with
the start date of subsequent pre-study flare. 

In the case that year of the end date of pre-study period is the same year of the start date 
of subsequent pre-study flare, then use the earliest date of both for imputation.
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred within the pre-study period. Then the minimum (earliest) of end 
date of pre-study period and start date of subsequent pre-study flare will be considered.
Changes in section 4.3 
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. 
An interim analysis is planned to be conducted after the last subject has completed the Week 48 
assessment. That is when each treated subject has completed the Week 48 Visit, or withdrawn 
prematurely. All data collected until the database cut-off date will be included. With this interim 
analysis, first study results will be available already about one year before the final analysis of 
the study. There is no intention to stop the study early for efficacy or for futility. The interim 
summaries and listings will be based on the same shells as for the final analysis, unless otherwise 
stated. The interim listings will include all data collected up to Week 48. The summary tables 
presenting results by visit will only consider results up to Week 48 Visit for the interim analysis. 
Summary tables of results not provided by visit, e.g. adverse events, concomitant medication, 
will not include events or medication that started after the Week 48 Visit. Data collected after 
Week 48 will not be presented in the interim analysis.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 58 of 92
No separate SAP will be created for the interim analyses, as all analyses will be covered within 
this SAP, and within the corresponding display specifications. In general, the interim analysis 
will follow the same specifications as the final analysis, unless stated differently in the 
corresponding sections. The interim analysis will include a subset of tables and listings that will 
be marked in the display specifications.
An additional interim data-cut might be needed to support a regulatory submission in nr-axSpA.
Has been changed to:
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. 
An interim analysis is planned to be conducted after the last subject has completed the Week 48 
assessment. That is when each treated subject has completed the Week 48 Visit, or withdrawn 
prematurely. All data collected until the database cut-off date will be included. With this interim 
analysis, first study results will be available already about one year before the final analysis of 
the study. There is no intention to stop the study early for efficacy or for futility. The interim 
summaries and listings will be based on the same shells as for the final analysis, unless otherwise 
stated. The interim listings will include all data collected up to Week 48. The summary tables 
presenting results by visit will only consider results up to Week 48 Visit for the interim analysis.
Summary tables of results not provided by visit, e.g. adverse events, will not include events or 
medication that started after the Week 48 Visit. Data collected after Week 48 will not be 
presented in the interim analysis.
The length of pre-study period and on-study period for collection of AU flares data will be 
48 weeks for the interim analysis, and will be 96 weeks for the final analysis. The analysis 
based on period length of 48 weeks will be repeated for the final analysis.
No separate SAP will be created for the interim analyses, as all analyses will be covered within 
this SAP, and within the corresponding display specifications. In general, the interim analysis 
will follow the same specifications as the final analysis, unless stated differently in the 
corresponding sections. The interim analysis will include a subset of tables and listings that will 
be marked in the display specifications.
An additional interim data-cut might be needed to support a regulatory submission in nr-axSpA.
Changes in section 6.2
The following sentence has been added at the end of section 6.2:
The responses to the following modified ASAS classification criteria for AS will be 
summarized for all subjects in a frequency table using the SS:
x
Back pain of ≥3 months and subject’s age at onset <45 years
x
Inflammatory back pain
x
Reactive arthritis
x
Enthesitis
x
Uveitis
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 59 of 92
x
Dactylitis
x
Psoriasis
x
Inflammatory bowel disease
x
HLA-B27
x
Elevated CRP (above upper limit of normal)
x
Sacroiliitis
Changes in section 8.1 (second paragraph)
The primary efficacy analysis hypothesis will be tested based on significance level of alpha 0.05 
and will be 2-sided. The entire alpha will be used for the primary efficacy analysis and analysis 
of the other secondary efficacy parameters will be supportive. Therefore, no alpha adjustment 
will be performed.
Has been changed to:
The primary efficacy analysis hypothesis will be tested based on significance level of alpha 0.05 
and will be 2-sided. The analysis of the other secondary efficacy parameters will be supportive. 
Therefore, no alpha adjustment for secondary efficacy variables will be performed. The alpha 
adjustment related to the formal interim review of data is described in Section 4.5.
Changes in section 8.1.1
The primary efficacy variable is the number of distinct episodes of AU flares in the Treatment 
Period. Per protocol, a flare is considered a new episode if a gap of at least 3 months occurs 
between 2 flares. If AU flare episodes as reported by the investigator occur less than 3 months 
(90 days) apart in the same eye, these will be programmatically corrected, such that a new AU 
flare within 3 months (90 days) after the end of the previous AU flare in the same eye will be 
considered as pertaining to the same AU episode. These flares will then be counted as one 
episode. Otherwise, if the time interval between 2 consecutive AU flares is greater than 3 months 
(90 days), or a separate eye is affected, the AU flares will be considered as separate episodes.
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if the flare 
occurs within the 12 months (365 days) prior to the start of study medication. An episode of AU 
flares is considered on-study, if the start date of flare is on or after the start date of study 
medication. Pre-study and on-study flares of the same eye will be combined if the time interval 
between the end of pre-study flare and the start of subsequent on-study flare is less than 3 
months (90 days). The resulting flare episode will be considered as pre-study flare episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes starts 12 months prior to 
Baseline, the pre-study period length for offset is 365 days for each subject. The on-study period 
length for offset is the time in days from start of study medication until last visit.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
from the start date of first AU flare episode until the Baseline visit date, and is categorized into 
<2 years and ≥2 years.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 60 of 92
Has been changed to:
The primary efficacy variable is the number of distinct episodes of AU flares in the Treatment 
Period. Per protocol, a flare is considered a new episode if a gap of at least 3 months occurs 
between 2 flares. If AU flare episodes as reported by the investigator occur less than 3 months
(90 days) apart in the same eye, these will be programmatically corrected, such that a new AU 
flare within 3 months (90 days) after the end of the previous AU flare in the same eye will be 
considered as pertaining to the same AU episode. These flares will then be counted as one 
episode. Otherwise, if the time interval between 2 consecutive AU flares is greater than 3 months
(90 days), or a separate eye is affected, the AU flares will be considered as separate episodes.
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if the flare 
occurs within the 96 weeks (672 days) prior to the start of study medication. For the interim 
analysis, an episode of AU flares is considered as pre-study if the flare occurs within 48 
weeks (336 days) prior to the start of study medication. An episode of AU flares is considered 
on-study, if the start date of flare is on or after the start date of study medication. Pre-study and 
on-study flares of the same eye will be combined if the time interval between the end of pre-
study flare and the start of subsequent on-study flare is less than 3 months (90 days). The 
resulting flare episode will be considered as pre-study flare episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes is extended to up to 2 
years prior to Baseline, the pre-study period length for offset is 672 days for each subject. The 
on-study period length for offset is the time in days from start of study medication until last visit.
For the interim analysis, an offset of 336 days will be used for the pre-study period, and the 
time in days from start of study medication until week 48 visit or early termination visit 
where applicable will be used.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
from the start date of first AU flare episode until the Baseline visit date, and is categorized into 
<2 years and ≥2 years.
Changes in section 8.2.2
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2008) as shown below:
x
0.121 x 
 (BASDAI Q2 result)
x
0.058 x 
 (BASDAI Q6 result)
x
0.110 x Patient’s Global Assessment of Disease Activity (PtGADA)
x
0.073 x 
(BASDAI Q3 result)
x
0.579 x (natural logarithm of the (CRP [mg/L] + 1))
, PtGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 61 of 92
If 1 component for the ASDAS is missing at a given visit, that component will be imputed by 
carrying the last observation forward, and the ASDAS will be calculated accordingly. If more 
than one component for the ASDAS is missing, ASDAS will be treated as missing.
For CRP values below the lower limit of quantification (<4mg/L), half the lower limit (2mg/L) 
will be used as the imputed value.
Disease activity categories based on ASDAS are as follows:
x
ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x
ASDAS-Moderate Disease (ASDAS-MD): ASDAS >=1.3, <2.1
x
ASDAS-High Disease Activity (ASDAS-HD): ASDAS >=2.1, <=3.5
x
ASDAS-very High Disease Activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinical Improvement (ASDAS-CI): ASDAS reduction (improvement) of >0
relative to Baseline
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline or has the lowest score possible post-baseline (i.e. when CRP<LLOQ and 
all other components are 0, then the minimum ASDAS score is 0.636 to 3 decimal places). 
Change from Baseline in ASDAS at Week 48 and Week 96 are secondary efficacy variables.
Has been changed to:
The ASDAS consists of a number of assessments which are scored by the subject and physician 
and multiplied by a proven formula (van der Heijde et al, 2008) as shown below:
x
0.121 x 
(BASDAI Q2 result)
x
0.058 x 
 (BASDAI Q6 result)
x
0.110 x Patient’s Global Assessment of Disease Activity (PtGADA)
x
0.073 x 
 (BASDAI Q3 result)
x
0.579 x (natural logarithm of the (CRP [mg/L] + 1))
PtGADA, 
 are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS.
If 1 component for the ASDAS is missing at a given visit, that component will be imputed by 
carrying the last observation forward, and the ASDAS will be calculated accordingly. If more 
than one component for the ASDAS is missing, ASDAS will be treated as missing.
For CRP values below the lower limit of quantification (<4mg/L), half the lower limit (2mg/L) 
will be used as the imputed value.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 62 of 92
The nomenclature of disease activity was updated by ASAS (Machado et al, 2018). The 
state ‘Moderate Disease Activity’ was replaced by ‘Low Disease Activity’ state. Disease 
activity categories based on ASDAS are as follows:
x
ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x
ASDAS-Low Disease Activity (ASDAS-LD): ASDAS >=1.3, <2.1
x
ASDAS-High Disease Activity (ASDAS-HD): ASDAS >=2.1, <=3.5
x
ASDAS-very High Disease Activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinical Improvement (ASDAS-CI): ASDAS reduction (improvement) of >0
relative to Baseline
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline or has the lowest score possible post-baseline (i.e. when CRP<LLOQ and 
all other components are 0, then the minimum ASDAS score is 0.636 to 3 decimal places). 
Change from Baseline in ASDAS at Week 48 and Week 96 are secondary efficacy variables.
Changes in section 11
The following reference was added:
Machado PM, Landewé R, Heijde Dv, et al. Ann Rheum Dis Epub ahead of print: 16 Feb 2018. 
Doi:10.1136/annrheumdis-2018-213184
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 63 of 92
13.3
AMENDMENT 3
Rationale for the amendment
This SAP was modified to implement decisions that were made before the fourth Data 
Evaluation Meeting. This includes the updated definitions of pre-study and on-study periods for 
the primary analysis to consider also AU flare episodes that occurred within 24 months (730 
days) prior to the start study medication and starting from Baseline until Week 96 or 
discontinuation visit and for supportive and sensitivity analysis to consider pre-study period as 
96 weeks (672 days) prior to start of study medication for counting flares and as the offset. In 
addition, the SAP was revised to make some minor administrative changes throughout.
Modifications and changes
Changes in section 1
The SAP is based on Amendment 2 of the Clinical Study Protocol, dated 17 Jan 2017.
Has been changed to:
The SAP is based on Amendment 3 of the Clinical Study Protocol, dated 22 Jan 2020.
Add section 2.1.4
The safety objectives of the study will be to evaluate the safety and tolerability of CZP therapy.
Changes in section 2.2.2
Safety variables to be assessed are: 
x
Adverse events (AEs)
x
Blood pressure
x
Physical examination
x
Clinical laboratory values (hematology, biochemistry, and urinalysis)
Has been changed to:
2.2.2.1 Secondary safety variable
The secondary safety variable to be assessed is treatment-emergent adverse events (TEAEs).
2.2.2.2 Other safety variables
The following other safety variables to be assessed are: 
x
Blood pressure
x
Physical examination
x
Clinical laboratory values (hematology, biochemistry, and urinalysis)
Changes in section 3.1
Unless stated otherwise, all inferential statistical tests will be 2-sided and conducted at the 0.05 
alpha level. Adjustment for multiplicity is described in Section 4.5. P-values for secondary 
efficacy variables are nominal. P-values will be presented to 3 decimal places.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 64 of 92
Has been changed to:
Unless stated otherwise, all inferential statistical tests will be 2-sided and conducted at the 0.05 
alpha level. Adjustment for multiplicity is described in Section 4.5. P-values for secondary 
efficacy variables are nominal. P-values will be presented to 3 decimal places and any values 
below 0.001 should be displayed as “<0.001”.
Changes in section 3.3
Unless otherwise specified, the last valid measurement before study medication administration 
will be utilized as Baseline value. For almost all variables, this will be the assessment made at 
the Baseline visit. However, for some variables, assessments may be scheduled for Screening 
only and not for Baseline. In this case the screening value will be utilized as baseline value. If a 
baseline measurement is missing, and a screening value available, the screening value will be 
utilized as Baseline instead. If a Baseline visit measurement is missing, and a Screening visit 
measurement is available, the Screening value will be utilized as Baseline. If a scheduled 
Baseline assessment is taken on the same day as first administration of study medication, it will 
be used as Baseline, irrespective of the time of the assessment relative to the first administration 
of study medication.
Has been changed to:
Unless otherwise specified, the last valid measurement before study medication administration 
will be utilized as Baseline value. For almost all variables, this will be the assessment made at 
the Baseline visit. However, for some variables, assessments may be scheduled for Screening 
only and not for Baseline. In this case the screening value will be utilized as baseline value. If a 
baseline measurement is missing, and a screening value available, the screening value will be 
utilized as Baseline instead. If a scheduled Baseline assessment is taken on the same day as first 
administration of study medication, it will be used as Baseline, irrespective of the time of the 
assessment relative to the first administration of study medication
Changes in section 3.4
Important protocol deviations (IPD) are deviations from the protocol which could potentially 
have a meaningful impact on study conduct, on the safety for an individual subject, or on the 
primary efficacy outcome for an individual subject. The criteria for identifying important 
protocol deviations will be defined within the specification of the IPD document. Important 
protocol deviations will be reviewed as part of the ongoing data cleaning process and all
important deviations will be identified and documented prior to database lock, although no 
analysis will be performed based on per protocol population. 
Important protocol deviations will be identified and classified by the deviation types defined in 
the IPD document. A listing of all important protocol deviations identified at the Data Evaluation 
Meeting will be presented for all subjects in the SS, and will include deviation type and 
description. The number and percentage of subjects in the ES with important protocol deviations 
will be summarized overall and by treatment.
Has been changed to:
Important protocol deviations (IPD) are deviations from the protocol which could potentially 
have a meaningful impact on study conduct, on the safety for an individual subject, or on the 
primary efficacy outcome for an individual subject. The criteria for identifying important 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 65 of 92
protocol deviations will be defined within the specification of the IPD document. Important 
protocol deviations will be reviewed as part of the ongoing data cleaning process and all 
important deviations will be identified and documented prior to database lock.
Important protocol deviations will be identified and classified by the deviation types defined in 
the IPD document. A listing of all important protocol deviations identified at the Data Evaluation 
Meeting will be presented for all subjects in the SS, and will include deviation type and 
description. The number and percentage of subjects in the SS with important protocol deviations 
will be summarized overall.
Changes in section 3.5.3
If the FAS differs from the SS, the efficacy analysis will be conducted using the FAS instead of 
the SS.
Has been changed to:
In case the FAS differs from the SS, the efficacy analysis will be conducted using the FAS 
instead of the SS.
Changes in section 3.9
As the BASMI is not collected, and there is no alternative measure of spinal mobility available in 
the study data, the complete component for spinal mobility is missing. Therefore the ASAS 5/6 
response criterion cannot be calculated, and the analysis of the secondary efficacy variable 
ASAS 5/6 has to be dropped. 
The clinical study protocol does not mention a PPS. This analysis set has been added, in order to 
additionally perform the primary efficacy analysis on the subset of protocol-compliant subjects.
ASDAS Clinical improvement was detailed as an “other” efficacy variable, but no definition was 
given. As there is no well-accepted definition, this variable has not been included in the analysis.
Has been changed to:
As the BASMI is not collected, and there is no alternative measure of spinal mobility available in 
the study data, the complete component for spinal mobility is missing. Therefore the ASAS 5/6 
response criterion cannot be calculated, and the analysis of the secondary efficacy variable 
ASAS 5/6 has to be dropped. 
The clinical study protocol does not mention a PPS. This analysis set has been added, in order to 
additionally perform the primary efficacy analysis on the subset of protocol-compliant subjects. 
In the calculation of ASDAS (Section 9.1.2 of the protocol), the CRP component was 
written as “0.579 × (natural logarithm of the CRP [mg/L] + 1)”, but should have been 
“0.579 × (natural logarithm of the (CRP [mg/L] + 1))”.
For BASDAI (Section 9.1.3 of the protocol), the protocol stated “The BASDAI is a 
validated self-reported instrument which consists of six 10-unit horizontal NRSs to 
 
 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 66 of 92
 
In Section 9.1.4 of the protocol, the pain assessment component of ASAS20/40/PR was 
defined as “the average of total and nocturnal spinal pain NRS scores”, but this should be 
defined as total spinal pain NRS score only.
ASDAS Clinical improvement was detailed as an “other” efficacy variable, but no definition was 
given. As there is no well-accepted definition, this variable has not been included in the analysis.
In Section 12.7 of the protocol, it stated that the interim analysis would use α=0.0001 and so 
the final analysis would use α=0.049. This should have said that α=0.001 would be used for 
the interim analysis.
Changes in section 4.2
Analysis based on observed case and last observation carried forward for continuous 
variables or non-responder imputation for categorical variables will be presented.
If the Baseline value is missing, the Screening value may be used as the Baseline. In general, if 
no measurement is available prior to receiving study medication, then the Baseline value is 
treated as missing, and will not be imputed. 
Post-Baseline values may only be imputed by carrying forward earlier post-Baseline values. 
Baseline values will not be carried forward to post-Baseline time points.
Premature withdrawal visits should be assigned to what would have been the next scheduled visit 
for the particular assessment that is being summarized. If a premature withdrawal visit occurs on 
the same date as a scheduled visit, then the assessments will be summarized with the scheduled 
visit.
Safety variables
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or 
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed 
values will be displayed in data listings).
x
Missing start day, but month and year present: If the start of study medication occurred in the 
same month and year as the occurrence of the AE/concomitant medication, the start day of 
the event/concomitant medication will be assigned to the day of first intake of study 
medication. Otherwise the start day will be set to the 1st day of the month.
x
Missing start day and month, but year present: If the start of study medication occurred in the 
same year as the occurrence of the AE/concomitant medication, the start day and month will 
be assigned to the date of first intake of study medication. Otherwise the start day and month 
will be set to January 1st.
x
Missing end day, but month and year present: The end day will be set to the last day of the 
month.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 67 of 92
x
Missing end day and month, but year present: If the maximum of the subject’s date of study 
termination or the date equivalent to 70 days after the subject’s last intake of study 
medication is the same year as the occurrence of the AE/Concomitant medication, then the 
end day and month will be set to the maximum of the date of study termination or the date 
equivalent to 70 days after last intake of study medication. Otherwise the end day will be set 
to December 31st of the given year.
Efficacy variables
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 days 
prior to Baseline until Baseline. The on-study period for the interim analysis is starting from 
Baseline until week 48, i.e. until study day 336. 
For the final analysis, the pre-study period is starting 96 weeks prior to Baseline, i.e. 672 days 
prior to Baseline until Baseline. The on-study period for the final analysis is starting from 
Baseline until week 96, i.e. until study day 672. In addition, the period definition used for 
interim with period length of 48 weeks will be repeated for the final analysis.
Pre-study period (48 vs 96 weeks prior to Baseline, i.e. 336 vs 672 days prior to Baseline, 
until Baseline for interim vs final analysis):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare, and the 
end date is clearly greater than end date of previous flare, then impute with the end date 
of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare, then use the latest date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare, then impute with the end date 
of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within the pre-study period. Then the maximum (latest) of start 
date of pre-study period and end date of previous flare will be considered.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 68 of 92
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

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flare before Baseline, then impute with the start date of subsequent pre-study flare. 

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year of the start date of subsequent pre-study flare, then use the earliest date of both for 
imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 

Year is the same as year of the start date of subsequent pre-study flare, then impute with 
the start date of subsequent pre-study flare. 

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of subsequent pre-study flare, then use the earliest date of both for imputation.
x
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date that the flare occurred within the pre-study period. Then the minimum (earliest) of end 
date of pre-study period and start date of subsequent pre-study flare will be considered.
On-study period (Baseline until end of treatment):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of study medication, then 
impute with the start date of study medication. 

Month and year are the same as month and year of the end date of previous on-study 
flare, and the end date is clearly greater than end date of previous on-study flare, then 
impute with the end date of previous on-study flare. 

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and year of the end date of previous on-study flare, then use the latest date of both for 
imputation.
x
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following conditions apply: 

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date of study medication. 

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end date of previous on-study flare. 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 69 of 92

In the case that year of the start date of study medication is the same year of the end date 
of previous on-study flare, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred after treatment start during the on-study period. Then the 
maximum (latest) of start date of study medication and end date of previous on-study flare 
eye will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

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impute with the end date of on-study period. 

Month and year are the same as month and year of the start date of subsequent on-study 
flare, then impute with the start date of subsequent on-study flare.
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imputation.
x
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following conditions apply:

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of on-study period. 

Year is the same as year of the start date of subsequent on-study flare, then impute with 
the start date of subsequent on-study flare. 

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subsequent on-study flare, then use the earliest date of both for imputation.
x
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date that the flare occurred after treatment start during the on-study period. Then the 
minimum (earliest) of end date of on-study period and start date of subsequent on-
study flare will be considered.
Has been changed to:
Analysis is based on observed case only.
If the Baseline value is missing, the Screening value may be used as the Baseline. In general, if 
no measurement is available prior to receiving study medication, then the Baseline value is 
treated as missing, and will not be imputed. 
Premature withdrawal visits should be assigned to what would have been the next scheduled visit 
for the particular assessment that is being summarized. If a premature withdrawal visit occurs on 
the same date as a scheduled visit, then the assessments will be summarized with the scheduled 
visit.
Safety variables
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 70 of 92
For analyses of AEs and concomitant medication usage, a complete date must be established in 
order to correctly identify the AE or medication as occurring during treatment or not. For 
purposes of imputing missing components of partially-reported start and stop dates for AEs and 
for medication use, the algorithms listed below will be followed. Start and stop dates of AEs or
concomitant medication will be displayed as reported in the subject data listings (i.e., no imputed 
values will be displayed in data listings).
x
Missing start day, but month and year present: If the start of study medication occurred in the 
same month and year as the occurrence of the AE/concomitant medication, the start day of 
the event/concomitant medication will be assigned to the day of first intake of study 
medication. Otherwise the start day will be set to the 1st day of the month.
x
Missing start day and month, but year present: If the start of study medication occurred in the 
same year as the occurrence of the AE/concomitant medication, the start day and month will 
be assigned to the date of first intake of study medication. Otherwise the start day and month 
will be set to January 1st.
x
If start day, month, and year are missing, start date will be replaced by the date of first study 
drug administration or by the first day of January of the year of the end date, if the first 
administration date is after the end date.
x
Missing end day, but month and year present: The end day will be set to the last day of the 
month.
x
Missing end day and month, but year present: If the maximum of the subject’s date of study 
termination or the date equivalent to 70 days after the subject’s last intake of study 
medication is the same year as the occurrence of the AE/Concomitant medication, then the 
end day and month will be set to the maximum of the date of study termination or the date 
equivalent to 70 days after last intake of study medication. Otherwise the end day will be set 
to December 31st of the given year.
Efficacy variables
The start and end dates of flares will be imputed for the analyses of AU flares data, in order to 
allow the calculation of time intervals between 2 consecutive flares and the duration of flares. 
Different rules will be applied for pre-study and on-study period flares.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 days 
prior to Baseline until Baseline. The on-study period for the interim analysis is starting from 
Baseline until week 48, i.e. until study day 336. 
For the final analysis, the pre-study period is starting 24 months prior to Baseline, i.e. 730 days 
prior to Baseline until Baseline. The on-study period for the final analysis is starting from 
Baseline until week 96, i.e. until the date of the Week 96 or discontinuation visit. In addition, 
sensitivity and supportive analyses use different definitions (as defined in Section 8.1.2).
Pre-study period:
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 71 of 92

Month and year are the same as month and year of the start date of pre-study period, then 
impute with the start date of pre-study period. 

Month and year are the same as month and year of the end date of previous flare in the 
same eye, and the end date is clearly greater than end date of previous flare in the same 
eye, then impute with the end date of previous flare. 

In the case that month and year of the start date of pre-study period is the same month 
and year of the end date of previous flare in the same eye, then use the latest date of both 
for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of pre-study period, then impute with the start 
date of pre-study period. 

Year is the same as year of the end date of previous flare in the same eye, then impute 
with the end date of previous flare. 

In the case that year of the start date of pre-study period is the same year of the end date 
of previous flare in the same eye, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred within the pre-study period. Then the maximum (latest) of start 
date of pre-study period and end date of previous flare in the same eye will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of pre-study period, then 
impute with the end date of pre-study period. 

Month and year are the same as month and year of the start date of subsequent pre-study 
flare in the same eye before Baseline, then impute with the start date of subsequent pre-
study flare. 

In the case that month and year of the end date of pre-study period is the same month and 
year of the start date of subsequent pre-study flare in the same eye, then use the earliest 
date of both for imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of pre-study period, then impute with the end 
date of pre-study period. 

Year is the same as year of the start date of subsequent pre-study flare in the same eye,
then impute with the start date of subsequent pre-study flare. 

In the case that year of the end date of pre-study period is the same year of the start date 
of subsequent pre-study flare in the same eye, then use the earliest date of both for 
imputation.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 72 of 92
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred within the pre-study period (of 2 years prior to baseline). Then 
the minimum (earliest) of end date of pre-study period (i.e. the day prior to treatment start 
date), the day prior to start date of subsequent pre-study flare in the same eye, or the 
start date plus the median duration of flare in that subject will be considered. The 
median duration of flare is determined from all flares recorded for that subject that 
have complete start and end dates (regardless of eye), including any flares prior to or 
during the pre-study period and on-study period.
On-study period (Baseline until end of treatment):
x
Missing start day, but month and year present: Impute the first day of the month unless one 
of the following conditions apply:  

Month and year are the same as month and year of the start date of study medication, then 
impute with the start date of study medication. 

Month and year are the same as month and year of the end date of previous on-study flare 
in the same eye, and the end date is clearly greater than end date of previous on-study 
flare in the same eye, then impute with the end date of previous on-study flare in the 
same eye.

In the case that month and year of the start date of study medication is the same month 
and year of the end date of previous on-study flare in the same eye, then use the latest 
date of both for imputation.
x
Missing start day and month, but year present: Impute January 1st unless one of the 
following conditions apply: 

Year is the same as year of the start date of study medication, then impute with the start 
date of study medication. 

Year is the same as year of the end date of previous on-study flare in the same eye, then 
impute with the end date of previous on-study flare in the same eye.

In the case that year of the start date of study medication is the same year of the end date 
of previous on-study flare in the same eye, then use the latest date of both for imputation.
x
Completely missing start dates of flares will only be imputed if it is clear based on the end 
date that the flare occurred after treatment start during the on-study period. Then the 
maximum (latest) of start date of study medication and end date of previous on-study flare in 
the same eye will be considered.
x
Missing end day, but month and year present: Impute the last day of the month unless one of 
the following conditions apply:

Month and year are the same as month and year of the end date of on-study period, then 
impute with the end date of on-study period. 

Month and year are the same as month and year of the start date of subsequent on-study 
flare in the same eye, then impute with the start date of subsequent on-study flare in the 
same eye.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 73 of 92

In the case that month and year of the end date of on-study period is the same month and 
year of the start date of subsequent on-study flare in the same eye, then use the earliest 
date of both for imputation.
x
Missing end day and month, but year present: Impute December 31st unless one of the 
following conditions apply:

Year is the same as year of the end date of on-study period, then impute with the end date 
of on-study period. 

Year is the same as year of the start date of subsequent on-study flare in the same eye,
then impute with the start date of subsequent on-study flare in the same eye.

In the case that year of the end date of on-study period is the same year of the start date of 
subsequent on-study flare in the same eye, then use the earliest date of both for 
imputation.
x
Completely missing end dates of flares will only be imputed if it is clear based on the start 
date that the flare occurred after treatment start during the on-study period. Then the start 
date of subsequent on-study flare in the same eye will be considered. Otherwise it will 
be assumed to be ongoing.
Changes in section 4.3
An additional interim data-cut might be needed to support a regulatory submission in nr-axSpA. 
Has been changed to:
An additional interim data-cut might be needed to support a regulatory submission in nr-axSpA 
or axSpA.
Changes in section 4.5
Although there is no intention to stop the study early due to efficacy or futility on the basis of the 
interim results, α=0.0001 will be spent in conjunction with this formal interim review of the data 
(Haybittle, 1971), and the final analysis of the primary efficacy variable will be conducted at the 
reduced 2-sided α-level of 0.049.
Has been changed to:
Although there is no intention to stop the study early due to efficacy or futility on the basis of the 
interim results, α=0.001 will be spent in conjunction with this formal interim review of the data 
(Haybittle, 1971), and the final analysis of the primary efficacy variable will be conducted at the 
reduced 2-sided α-level of 0.049.
Changes in section 4.8
Not applicable
Has been changed to:
The primary efficacy variable will be summarized using the following subgroups:
x
Gender (Male, Female)
x
Age (<median, >=median)
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 74 of 92
x
axSpA subpopulation as determined by the investigator (Ankylosing Spondylitis, 
non-radiographic axial spondyloarthritis)
A Poisson regression model as described for the primary analysis will be used including 
terms for the subgroup and the subgroup by treatment period interaction. The results will 
be presented, but no p-values will be given.
Changes in section 6.1
Tables with descriptive statistics and listings will be given for the demographic variables age (at 
time of informed consent), gender, weight and height at Baseline, race, ethnicity, body mass 
index (BMI), and body surface area (BSA). Demographic characteristics will be summarized for 
the SS. 
The age will be calculated with the documented year of birth, January as imputed month and 1 as 
imputed day of birth, at the time of informed consent, as follows:
Has been changed to:
Tables with descriptive statistics and listings will be given for the demographic variables age (at 
time of informed consent), gender, weight and height at Baseline, race, ethnicity, body mass 
index (BMI), and body surface area (BSA) as calculated below. Demographic characteristics 
will be summarized for the SS. 
Only the year of birth has been collected, so the age will be calculated with the documented 
year of birth, January as imputed month and 1 as imputed day of birth, at the time of informed 
consent, as follows:
Changes in section 6.2
Disease duration of axSpA will be calculated as the difference between the date of Baseline visit 
and the onset date of axSpA as documented on the medical history pages. If the onset date of 
axSpA is partial, it will be imputed to the most recent feasible date (ie, last day of the month if 
only day is missing, or the last day of the year if day and month are missing). Disease duration 
of axSpA will be summarized as continuous variable in days, as well as categorized into <2 
years and ≥2 years.
Time since onset of first uveitis flare will be calculated as the difference between the date of 
Baseline visit and the onset date of first uveitis flare. If the onset date of first uveitis flare is 
partial, it will be imputed to the last feasible date (ie, first day of the month if only day is 
missing, or the first day of the year if day and month are missing). Time since onset of first 
uveitis flare will be summarized as continuous variable in days, as well as categorized into <2 
years and ≥2 years.
Has been changed to:
Disease duration of axSpA will be calculated as the difference between the date of Baseline visit 
and the onset date of Axial spondyloarthritis or Ankylosing spondylitis as documented on the 
medical history pages. If the onset date of axSpA is partial, it will be imputed to the most recent 
feasible date (ie, first day of the month if only day is missing, or the first day of the year if day 
and month are missing). Disease duration of axSpA will be summarized as continuous variable 
in years, as well as categorized into <2 years and ≥2 years.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 75 of 92
Time since onset of first uveitis flare will be calculated as the difference between the date of 
Baseline visit and the onset date of first uveitis flare. If the onset date of first uveitis flare is 
partial, it will be imputed to the most recent feasible date (ie, first day of the month if only day 
is missing, or the first day of the year if day and month are missing). Time since onset of first 
uveitis flare will be summarized as continuous variable in years, as well as categorized into <2 
years and ≥2 years.
If medical history terms of back pain or inflammatory back pain are missing for a subject, 
then the terms axial spondyloarthritis or Ankylosing spondylitis will used instead.
Changes in section 6.3
The Medical history contains any previous or ongoing medical conditions that occurred prior to 
study entry. They will be listed for all subjects in the ES including the reported term, start date 
(month and year only), end date (month and year only) (or ongoing if applicable) and the 
information whether the procedure is related to axSpA. 
Has been changed to:
The Medical history contains any previous or ongoing medical conditions that occurred prior to 
study entry. They will be listed for all subjects in the SS including the reported term, start date 
(month and year only), end date (month and year only) (or ongoing if applicable) and the 
information whether the procedure is related to axSpA. 
Changes in section 6.4
A medication can be defined as both prior and concomitant. Where a medication start or stop 
date is (partially) missing, the medication will be considered a concomitant medication, unless 
the partial data is suggesting otherwise. Imputation of dates will follow the rules described in 
section Section 4.2 . Concomitant medications will be summarized for subjects in the SS. The 
following information will be included in the listings: reported term, dose per intake and dose 
unit, frequency, formulation, route, indication, start and stop dates (including relative study day), 
and in case of missing stop date, the information whether the intake of medication is ongoing. 
Intake of any new prohibited medication since last visit is collected and presented in a separate 
listing.
Has been changed to:
A medication can be defined as both prior and concomitant. Where a medication start or stop 
date is (partially) missing, the medication will be considered a concomitant medication, unless 
the partial data is suggesting otherwise. Imputation of dates will follow the rules described in 
section Section 4.2 . Concomitant medications will be summarized for subjects in the SS. The 
following information will be included in the listings: reported term, dose per intake and dose 
unit, frequency, formulation, route, indication, start and stop dates (including relative study day), 
and in case of missing stop date, the information whether the intake of medication is ongoing.
Past medication summaries will be generated for disease-modifying antirheumatic drugs 
(DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and anti-tumor necrosis 
factors (anti-TNFs) by anatomical therapeutic chemical (ATC) Anatomical Main Group 
(ATC Level 1), Pharmacological Subgroup (ATC level 3), and PT). 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 76 of 92
Concomitant DMARDs and NSAIDs will be summarized by WHO-DD Anatomical Main 
Group (ATC Level 1), Pharmacological Subgroup (ATC level 3), and PT). Concomitant 
medications other than DMARDs and NSAIDs will also be summarized.
Intake of any new prohibited medication since last visit is collected and presented in a separate 
listing.
Changes in section 7
There will be 2 approaches to calculate treatment compliance. The first will utilize the number of 
administered syringes and compare them to the scheduled expected number of syringes. Two 
syringes should be administered for the loading doses (at weeks 0, 2 and 4) however only 1 
syringe should be administered at any other visit. The difference in number of syringes between 
the total actual used and the total expected syringes will be summarized. In addition, a ratio of 
compliance will be further computed based on the number of actual and expected syringes. The 
ratio of compliance will be summarized as a continuous variable and categorically (<0.80, ≥0.80-
≤1.0 and >1.0). The general formula for the compliance ratio (CR) is given as follows: 
CR = # actual syringes / # expected syringes
The second approach defines compliance with study drug administration based upon comparing 
the actual day of administration with the expected day of administration. The expected day of 
administration will be based upon the Baseline date. The sum of the absolute difference in days 
between the actual and expected days will be summarized. In addition, a ratio of compliance will 
be further computed based upon the actual and expected day. The ratio of compliance will also 
be summarized as a continuous variable and categorically (<0.80, ≥0.80-≤1.0 and >1.0). The 
general formula for the compliance ratio based on duration (CRD) is given as follows:
CRD = (Study Duration - Cumulative Difference) / Study Duration
The CRD ranges between 0 and 1. To calculate study duration, the date of the Week 96 visit or 
the last injection date prior to study treatment discontinuation will be compared to the Baseline 
date, as shown below:
Study Duration (days) = Week 96 visit/last injection date – Baseline date (maximum value is 
675 days)
Cumulative Difference (days) = sum (ABS [actual date – scheduled date])
The sum will be calculated for the 11 visits from Week 0 (Baseline) to Week 84, and for all 
planned home administrations from week 6 to week 94. In case the actual day of administration 
is missing, the maximum deviation to the scheduled day will be assumed (ie, 14 days). If, for a 
scheduled day with 2 planned injections, the syringes were administered on 2 different days, the 
maximum day difference of the 2 actual dates to the scheduled date will be utilized.
Has been changed to:
There will be 2 approaches to calculate treatment compliance. The first will utilize the number of 
administered syringes and compare them to the scheduled expected number of syringes. Two 
syringes should be administered for the loading doses (at weeks 0, 2 and 4) however only 1 
syringe should be administered at any other visit from Week 6 until Week 94/last scheduled 
injection. The difference in number of syringes between the total actual used and the total 
expected syringes will be summarized. In addition, a ratio of compliance will be further 
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21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 77 of 92
computed based on the number of actual and expected syringes. The ratio of compliance will be 
summarized as a continuous variable and categorically (<0.80, ≥0.80-≤1.0 and >1.0). The 
general formula for the compliance ratio (CR) is given as follows: 
࡯ࡾൌ
ࡺࡿ̴࢟࢘ࢇࢉ࢚
ࡺࡿ̴࢟࢘ࢋ࢞࢖
where NSyr_act is the number of actual injections and NSyr_exp is the number of expected 
injections. The second approach defines compliance with study drug administration based upon 
comparing the actual day of administration with the expected day of administration. The 
expected day of administration will be based upon the Baseline date and the previous injection 
date. The sum of the absolute difference in days between the actual and expected days will be 
summarized. In addition, a ratio of compliance will be further computed based upon the actual 
and expected day. The ratio of compliance will also be summarized as a continuous variable and 
categorically (<0.80, ≥0.80-≤1.0 and >1.0). The general formula for the compliance ratio based 
on duration (CRD) is given as follows:
࡯ࡾࡰൌࢀࡰ̴࢛࢙࢚࢛࢘െο࡯࢛࢓
ࢀࡰ̴࢛࢙࢚࢛࢘
where TDur_stu is the study duration and 'Cum is the cumulative difference between actual 
and scheduled day of administration. 
Specific details of this formula are provided in Appendix 12.1 (Compliance Ratio 
Calculation).
The CRD ranges between 0 and 1. To calculate study duration, the date of the Week 94 visit or 
the last injection date prior to study treatment discontinuation will be compared to the Baseline 
date, as shown below:
Study Duration (days) = Week 94 visit/last injection date – Baseline date + 14 
The sum will be calculated for the 11 visits from Week 0 (Baseline) to Week 84, and for all 
planned home administrations from week 6 to week 94. In case the actual day of administration 
is missing, the maximum deviation to the scheduled day will be assumed (ie, 14 days). If, for a 
scheduled day with 2 planned injections, the syringes were administered on 2 different days, the 
maximum day difference of the 2 actual dates to the scheduled date will be utilized.
Changes in section 8
The efficacy analysis will be based on all subjects in the SS or FAS, as appropriate. If there is no 
missing AU flare incidence data from pre-study period, the FAS will be the same as the SS. If 
there is missing AU flare incidence data from the pre-study period, the FAS will be used 
instead of the SS. The primary efficacy analysis will additionally be repeated for the PPS.
Has been changed to:
The efficacy analysis will be based on all subjects in the SS or FAS, as appropriate. If there is no 
missing AU flare incidence data from pre-study period, the FAS will be the same as the SS. The 
FAS will be used for analyses of the primary variable and the SS will be used for all other 
efficacy analyses. The primary efficacy analysis will additionally be repeated for the PPS.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 78 of 92
Changes in section 8.1
The primary efficacy analysis will consist of a comparison of the frequency of AU flares during 
the pre-study/historical period with that observed while in the study during CZP treatment. It is 
assumed that the frequency of AU flares follows a Poisson distribution. As such, the analysis 
will be performed as a generalized estimating equations analysis for Poisson outcome that will 
take into account the possible within-subject correlation (between the retrospective and 
prospective AU flare counts). The model will contain 2 records per subject corresponding to the 
frequency of AU flares before study and during the study, offset by log-time of each of the 
reporting periods. Disease duration of axSpA will be included as a factor in the model, initially 
defined as <2 years and ≥2 years; the specific cutoffs for analysis may deviate from this based on 
the distribution seen in the data. The p-value for effect of CZP treatment on frequency of AU 
flares, along with rate ratio (CZP/historical) and 95% confidence interval, will be obtained from 
this model.
The primary efficacy analysis hypothesis will be tested based on significance level of alpha 0.05 
and will be 2-sided. The analysis of the other secondary efficacy parameters will be supportive. 
Therefore, no alpha adjustment for secondary efficacy variables will be performed. The alpha 
adjustment related to the formal interim review of data is described in Section 4.5.
Statistical Model
Let Yij be the number of AU flare episodes for subject i in period j, where tij is the length of the 
interval. It is assumed that the responses within a subject are correlated. For the statistical model 
assumptions about the correlation structure need to be done. Assuming an exchangeable 
correlation structure means that correlation between any two responses of the ith individual is the 
same. Also we account for different interval length by adding the offset term log(tij). The mean 
of the Poisson distribution is E(Yij)= μij, and the mean response per unit time is μij/tij. The 
Poisson model using a log-link can be written as
Log(μij) = β0 + β1*x1ij + β2*x2ij + log(tij)
which resolves to μij = tij*exp(β0)*exp(β1*x1ij)*exp(β2*x2ij), with the variables
x1ij: variable for period: 1 on-study, 0 pre-study
x2ij: variable for disease duration of axSpA: <2 years, ≥2 years
Has been changed to:
The primary efficacy analysis will consist of a comparison of the frequency of AU flares during 
the pre-study/historical period with that observed while in the study during CZP treatment. It is 
assumed that the frequency of AU flares follows a Poisson distribution. As such, the analysis 
will be performed as a generalized estimating equations analysis for Poisson outcome that will 
take into account the possible within-subject correlation (between the retrospective and 
prospective AU flare counts). The model will contain 2 records per subject corresponding to the 
frequency of AU flares before study and during the study, offset by log-time of each of the 
reporting periods. Disease duration of axSpA will be included as a factor in the model, initially 
defined as <2 years and ≥2 years; the specific cutoffs for analysis may deviate from this based on 
the distribution seen in the data. The p-value for effect of CZP treatment on frequency of AU 
flares, along with rate ratio (CZP/historical) and 95% confidence interval, will be obtained from 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 79 of 92
this model. The rate per 96 weeks and rate per year for each study period from the model 
will also be presented.
The primary efficacy analysis hypothesis will be tested based on significance level of alpha 0.05 
and will be 2-sided. The analysis of the other secondary efficacy parameters will be supportive. 
Therefore, no alpha adjustment for secondary efficacy variables will be performed. The alpha 
adjustment related to the formal interim review of data is described in Section 4.5.
Statistical Model
Let Yij be the number of AU flare episodes for subject i in period j, where tij is the length of the 
interval. It is assumed that the responses within a subject are correlated. For the statistical model 
assumptions about the correlation structure need to be done. Assuming an exchangeable 
correlation structure means that correlation between any two responses of the ith individual is the 
same. Also we account for different interval length by adding the offset term log(tij). The mean 
of the Poisson distribution is E(Yij)= μij, and the mean response per unit time is μij/tij. The 
Poisson model using a log-link can be written as
ܔܗ܏ࣆ࢏࢐ൌࢼ૙൅ࢼ૚࢞૚Ǣ࢏࢐൅ࢼ૛࢞૛Ǣ࢏൅ܔܗ܏࢚࢏࢐
which resolves to 
ࣆ࢏࢐ൌ࢚࢏࢐܍ܠܘሺࢼ૙ሻכ ܍ܠܘ൫ࢼ૚࢞૚Ǣ࢏࢐൯כ ܍ܠܘሺࢼ૛࢞૛Ǣ࢏ሻ
with the variables
x1ij: variable for period: 1 on-study, 0 pre-study
x2i: variable for disease duration of axSpA: <2 years, ≥2 years
Changes in section 8.1.1
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if the flare 
occurs within the 96 weeks (672 days) prior to the start of study medication. For the interim 
analysis, an episode of AU flares is considered as pre-study if the flare occurs within 48 weeks 
(336 days) prior to the start of study medication. An episode of AU flares is considered on-study, 
if the start date of flare is on or after the start date of study medication. Pre-study and on-study 
flares of the same eye will be combined if the time interval between the end of pre-study flare 
and the start of subsequent on-study flare is less than 3 months (90 days). The resulting flare 
episode will be considered as pre-study flare episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes is extended to up to 2 
years prior to Baseline, the pre-study period length for offset is 672 days for each subject. The 
on-study period length for offset is the time in days from start of study medication until last visit. 
For the interim analysis, an offset of 336 days will be used for the pre-study period, and the time 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 80 of 92
in days from start of study medication until week 48 visit or early termination visit where 
applicable will be used.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated 
from the start date of first AU flare episode until the Baseline visit date, and is categorized 
into <2 years and ≥2 years.
Has been changed to:
Pre-study and on-study AU flare episodes will be counted. An episode of AU flares is considered 
as pre-study, if the start date of flare is before the start date of study medication and if the start 
date of flare occurs within the 24 months (730 days) prior to the start of study medication. For 
the interim analysis, an episode of AU flares is considered as pre-study if the flare occurs within 
48 weeks (336 days) prior to the start of study medication.
For the Week 96 (primary) analysis, an episode of AU flares is considered on-study, if the start 
date of flare is on or after the start date of study medication and the start date of the flare 
occurs up to and including the last visit in the treatment period, i.e. Week 96 or 
discontinuation visit.
Pre-study and on-study flares of the same eye will be combined if the time interval between the 
end of pre-study flare and the start of subsequent on-study flare is less than 3 months (90 days). 
The resulting flare episode will be considered as pre-study flare episode.
The log-time offset in the Poisson model will consist of the length of pre-study and on-study 
reporting periods in days. As the documentation of pre-study episodes is extended to up to 2 
years prior to Baseline, the pre-study period length for offset is 730 days for each subject, 
unless the date of first uveitis flare is within 2 years of baseline, in which case the pre-study 
period length will be from date of first uveitis flare until baseline. The on-study period length 
for offset is the time in days from start of study medication until last visit, i.e. Week 96 or 
discontinuation visit. For the interim analysis, an offset of 336 days will be used for the pre-
study period or time since first uveitis flare if shorter than 336 days, and the time in days 
from start of study medication until week 48 visit (taken as 336 days) or early termination visit
(taken as 14 days after the last treatment) where applicable will be used for the on-study 
period.
Disease duration of axSpA, which will be included in the Poisson model as a factor, is calculated
as defined in Section 6.2, and is categorized into <2 years and ≥2 years.
Changes in section 8.1.2
The AU flare rate (event rate) per 100 patient-years of exposure, both before and during 
the study will be calculated. The corresponding rate ratio along with 95% confidence 
interval (Garwood, 1936) will be presented as a key supportive analysis to the primary 
efficacy analysis results (see Section 8.2.1 ).
Has been changed to:
The primary analysis will be repeated using the pre-study period as 96 weeks (672 days) 
prior to start of study medication for counting flares and as the offset, instead of 24 
months. The on-study period will be the same as that used for the primary analysis.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 81 of 92
In addition, the analysis for the full 2 years before and after study medication will be 
provided. The pre-study period will be the 2 years (730 days) prior to start of study 
medication, which will be used for counting flares and as the offset. The on-study period 
will be determined for whose episodes of AU flares for which the start date of flare is on or 
after the start date of study medication and up to and including the SFU visit or date of last 
administration of study medication + 70 days.
An analysis for the first 48 weeks will also be produced. The period for pre-study will be 
the 12 months (365 days) prior to start of study medication, which will be used for counting 
flares and as the offset. An episode of AU flares will be considered on-study, if the start 
date of flare is on or after the start date of study medication and up to and including the 
Week 48 visit or discontinuation visit if prior to Week 48. The exact date of the Week 48 or 
discontinuation visit will be used for each subject. This analysis will also be repeated using 
48 weeks (336 days) as the pre-study period for counting flares and as offset, but keeping 
the on-study period of 48 weeks the same (i.e. using the exact date of the Week 48 or 
discontinuation visit).
The primary efficacy analysis will be repeated in the subgroup of subjects excluding those 
with any pre-study flares with completely missing end dates in the 2 years prior to baseline. 
Subjects will be excluded if any of the flares that started within the 2 years prior to baseline 
have completely missing end dates (i.e. no day, month or year).
Changes in section 8.2.1
Number of AU flares
Has been changed to:
Number of AU flares per 100 patient-years
Changes in section 8.2.2
, PtGADA, 
are all 
assessed on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS.
If 1 component for the ASDAS is missing at a given visit, that component will be imputed by 
carrying the last observation forward, and the ASDAS will be calculated accordingly. If more 
than one component for the ASDAS is missing, ASDAS will be treated as missing.
For CRP values below the lower limit of quantification (<4mg/L), half the lower limit (2mg/L) 
will be used as the imputed value.
The nomenclature of disease activity was updated by ASAS (Machado et al, 2018). The state 
‘Moderate Disease Activity’ was replaced by ‘Low Disease Activity’ state. Disease activity 
categories based on ASDAS are as follows:
x
ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x
ASDAS-Low Disease Activity (ASDAS-LD): ASDAS >=1.3, <2.1
x
ASDAS-High Disease Activity (ASDAS-HD): ASDAS >=2.1, <=3.5
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 82 of 92
x
ASDAS-very High Disease Activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinical Improvement (ASDAS-CI): ASDAS reduction (improvement) of >0 
relative to Baseline
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline or has the lowest score possible post-baseline (i.e. when CRP<LLOQ
and all other components are 0, then the minimum ASDAS score is 0.636 to 3 decimal 
places).
Has been changed to:
, PtGADA, 
are all assessed 
on a numerical scale (0 to 10 units) (Lukas et al, 2009).
The sum of these weighted components gives the ASDAS.
If 1 component for the ASDAS is missing at a given visit, that component will be imputed by 
carrying the last observation forward, and the ASDAS will be calculated accordingly. If more 
than one component for the ASDAS is missing, ASDAS will be treated as missing.
For CRP values below the lower limit of quantification (<4mg/L), half the lower limit (2mg/L) 
will be used as the imputed value. This approach will be used for summaries of CRP as well.
The nomenclature of disease activity was updated by ASAS (Machado et al, 2018). The state 
‘Moderate Disease Activity’ was replaced by ‘Low Disease Activity’ state. Disease activity 
categories based on ASDAS are as follows:
x
ASDAS-Inactive Disease (ASDAS-ID): ASDAS <1.3
x
ASDAS-Low Disease Activity (ASDAS-LD): ASDAS >=1.3, <2.1
x
ASDAS-High Disease Activity (ASDAS-HD): ASDAS >=2.1, <=3.5
x
ASDAS-very High Disease Activity (ASDAS-vHD): ASDAS >3.5
The variables related to ASDAS clinical improvement are defined as follows:
x
ASDAS-Clinically Important Improvement (ASDAS-CII): ASDAS reduction (improvement) 
of >=1.1 relative to Baseline
x
ASDAS-Major Improvement (ASDAS-MI): ASDAS reduction (improvement) of >=2.0 
relative to Baseline. 
Changes in sections 8.2.5, 8.2.6, 8.2.7, 8.2.8
The data including the change from baseline at Week 48 and Week 96 will be summarized.
Has been changed to:
The data including the change from baseline at Week 48 and Week 96 will be summarized as
secondary endpoints.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 83 of 92
Changes in section 8.3
Has been addeed:
All other efficacy endpoints with exception of flare duration and severity will be tabulated at all 
time points acc to assessment schedule.
Changes in section 8.3.1
For each subject in FAS, the mean duration of on-study AU flares, and the maximum severity 
of on-study AU flares will be determined and summarized. The duration of an episode of AU 
flare is calculated as follows: 
Duration (days) = end date of flare – start date of flare +1. 
For uveitis flare, the highest grade (severity) noted during an episode of uveitis will be graded 
as follows: 
Grade 0=None; Grade 1+=Faint; Grade 2+=Moderate, iris and lens details clear; 
Grade3+=Marked, iris and lens details hazy; Grade4+=Intense, fibrin or plastic aqueous; 
ND=Not done or not assessed; UNK=Unknown
Has been changed to:
For each subject in FAS, the total duration and the maximum severity of pre-study and on-
study AU flares will be determined and summarized. The duration of an episode of AU flare 
(TDur_Fl) is calculated as follows: 
ࢀࡰ̴࢛࢘ࡲ࢒ൌࡰࢇ࢚ࢋࡱ࢔ࢊ̴ࡲ࢒െࡰࢇ࢚ࢋࡿ࢚ࢇ࢚࢘ࡲ࢒൅૚
with DateEnd_Fl and DateStart_FL the end date and start date of flare, respectively. 
The duration of pre-study and on-study periods is defined in Section 4.2.
For the interim analysis, the pre-study period is starting 48 weeks prior to Baseline, i.e. 336 
days prior to Baseline until Baseline. The on-study period for the interim analysis is 
starting from Baseline until week 48, i.e. until study day 336. 
For the final analysis, the pre-study period is starting 24 months prior to Baseline, i.e. 730 
days prior to Baseline until Baseline. The on-study period for the final analysis is starting 
from Baseline until week 96, i.e. until the date of the Week 96 or discontinuation visit.
The highest grade (severity) of uveitis flare across all flares per subject will be summarized. 
The highest grade (severity) noted during an episode of uveitis will be graded as follows:
Grade 0=None; Grade 1+=Faint; Grade 2+=Moderate, iris and lens details clear; 
Grade3+=Marked, iris and lens details hazy; Grade4+=Intense, fibrin or plastic aqueous; 
ND=Not done or not assessed; UNK=Unknown.
Changes in section 8.3.2
Extra-articular assessments (eg, number of IBD exacerbations [in subjects with concurrent 
IBD] and number of psoriasis exacerbations [in subjects with concurrent psoriasis]) are to be 
performed at Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, and at Completion at Week 
96/WD Visit. At each visit, the number of episodes since the last visit and the number of days 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 84 of 92
with IBD/psoriasis are collected. Episodes are considered equivalent to exacerbations. These 
data will be summarized using summary statistics for continuous variables.
Has been changed to:
Extra-articular assessments (eg, number of IBD exacerbations and number of psoriasis 
exacerbations) are to be performed at Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, and 
at Completion at Week 96/WD Visit. At each visit, the number of episodes since the last visit 
and the number of days with IBD/psoriasis are collected. Episodes are considered equivalent to 
exacerbations. These data will be summarized using summary statistics for continuous variables.
Changes in section 8.3.5:
For the calculation of the SF-36 domain scores and the component summaries PCS and MCS, the 
scoring software QualityMetric Health Outcomes™Scoring Software 4.5 will be used. The norm-
based scores (based on the US general population) will be utilized for analysis.
Has been changed to:
For the calculation of the SF-36 domain scores and the component summaries PCS and MCS, the 
scoring software QualityMetric Health Outcomes™Scoring Software 4.5 will be used. The norm-
based scores (based on the US general population for 2009) will be utilized for analysis.
Changes in section 10.1:
The number of doses received will be summarized with continuous statistics for the SS. 
The duration of exposure is calculated as follows:
Exposure duration = Date of last dose of study medication – date of first dose of study 
medication + 14 days
The cumulative duration of exposure will be summarized for subjects exposed for at least one 
day, ≥183 days, ≥365 days, ≥548 days, ≥730 days. 
Additionally, the subject time at risk will be summarized. Subject time at risk (in days) is 
calculated as:
Date of last administration of study medication – date of first administration + 70 days 
(except where a change of treatment or last clinical contact occurs prior to completion of 
this 70-day period. Date of last clinical contact per subject is the defined as the maximum of 
[last visit date including safety follow-up visits, last imputed AE start date, last date of 
termination or completion, last date of study drug administration, clinical cutoff date for ongoing 
studies, death date]).
In cases where the date of last clinical contact occurs prior to completion of this 70-day period,
subject time at risk (in days) will be calculated as:
Date of last clinical contact – date of first administration+1. 
The study medication duration will be listed together with the dates of first and last study 
medication administration.
Has been changed to:
The number of doses received will be summarized with continuous statistics for the SS. 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 85 of 92
Duration of exposure to study medication will be calculated as:
int
d
date
date
Dur
First
Last
Exp


 
where dint represents the dosing interval of 14 days.
The cumulative duration of exposure will be summarized for subjects exposed for at least one 
day, ≥183 days, ≥365 days, ≥548 days, ≥730 days. 
Additionally, the subject time at risk will be summarized. Subject time at risk (in days) is 
calculated as:


2
1
*
5 t
date
date
T
First
Last
Risk


 
where t1/2 is 14 days.
If there is a change of treatment or the last clinical contact occurs prior to completion of 
the follow-up period, the date of last clinical contact per subject is defined as the maximum of 
[last visit date including safety follow-up visits, last imputed AE start date, last date of 
termination or completion, last date of study drug administration, death date] or the clinical 
cutoff date for ongoing studies if earlier than this maximum date).
In cases where the date of last clinical contact (LastCC) occurs prior to completion of this 
follow-up period, subject time at risk (in days) will be calculated as:
1


 
First
LastCC
Risk
date
date
T
Subject years at risk is the sum of all relevant subject time at risk (in days) divided by 
365.25.
The study medication duration will be listed together with the dates of first and last study 
medication administration.
Changes in section 10.2:
Tables showing TEAEs, serious TEAEs, non-serious TEAEs, TEAEs leading to discontinuation 
of study drug, TEAEs by maximum intensity, TEAEs by relationship, serious TEAEs by 
relationship, fatal TEAEs by relationship, TEAEs including subject numbers will be provided on 
the SS.
Additionally, more detailed summaries of TEAEs will be presented, which include the exposure 
adjusted incidence rate (EAIR) with associated 95% confidence interval, and the exposure 
adjusted event rate (EAER). For EAIR, the numerator will be the total number of subjects 
experiencing the AE of interest. The denominator will be 100 patient-years; that is, the 
total summation of individual patient-years at risk up to the first occurrence of the AE of 
interest for subjects with that AE, and the total patient-years at risk for those subjects not 
experiencing that AE, divided by 100. EAIRs will be presented with a 95% exact 
confidence interval based upon the Chi-Square distribution (Ulm, 1990). For EAERs, the 
numerator will be the number of AEs including repeat occurrences in individual subjects; 
the denominator will be 100 patient-years.  That is, the total summation of individual 
patient-years at risk divided by 100. No confidence interval will be computed for EAER.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 86 of 92
Subject time at risk represents the time a subject was at risk for having an AE. The 
derivation is described in Section 10.1 .Subject years at risk is the sum of all relevant 
subject time at risk (in days) divided by 365.25.
Where an AE start date is (partially) missing, the AE will be considered TE if possible. 
Imputation rules provided in Section 4.2 are based on the assumption that if the start date is 
incomplete, either day only is missing, or day and months are missing, or date is completely 
missing. Although the algorithms for treatment-emergence depend on the onset date, imputation 
rules are provided for resolution date as well, as these may be needed for certain statistical 
analyses, such as an analyses of AE prevalence or AE duration.
Listings based on SS for all AEs will be provided. A glossary for the reported terms will also be
generated utilizing SOC, HLT, and PT.
Anticipated SAEs, as described in Section 10.5 of the clinical study protocol, will not be 
summarized either by any additional tables or listings, as they are included in the standard AE 
summaries.
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:
x
Opportunistic infections
x
Malignant and unspecified tumors
x
Malignant tumors
x
Serious cardiovascular events
x
Demyelinating-like disorders
x
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x
Serious bleeding events
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:
x
Serious infections 
x
Congestive heart failure
x
Lupus and lupus-like illness
x
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following notes to AEs of interest in the clinical study protocol are given for reporting 
purposes only, and therefore will not be summarized separately: A confirmed LTBI must be 
reported as an AE of interest. Confirmed active TB is an AE of interest. In the event that an 
active TB occurrence meets the protocol’s SAE criteria, it is also an SAE. Potential Hy’s Law, 
defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality is also considered an AE of interest.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 87 of 92
The following events are not officially considered to be AEs of interest but are nonetheless 
considered to be interesting enough to be summarized in stand-alone tables:  1) Hepatic events 
and 2) Hypersensitivity reactions and anaphylactic reactions.
The approach for summarizing AEs of interest is detailed in the UCB AE of interest program 
specifications for Cimzia.
Data collected on hospitalization will be presented in a listing.
Has been changed to:
Tables showing TEAEs, serious TEAEs, non-serious TEAEs, TEAEs leading to discontinuation 
of study drug, TEAEs by maximum intensity, TEAEs by relationship, serious TEAEs by 
relationship, fatal TEAEs by relationship, TEAEs including subject numbers will be provided on 
the SS.
Additionally, more detailed summaries of TEAEs will be presented, which include the exposure 
adjusted incidence rate (EAIR) with associated 95% confidence interval, and the exposure 
adjusted event rate (EAER). 
The EAIR is defined as the number of subjects (n) with a specific AE adjusted for the 
exposure and will be scaled to 100 patient-years:
¦
 

 
N
i
i
Exp
T
n
EAIR
1
,
100
If a subject has multiple events, the time of exposure is calculated to the first occurrence of 
the AE of interest. If a subject has no events, the total time at risk is used.
Exact Poisson 95% confidence intervals for incidence rates are calculated using the 
relationship between the Poisson and the Chi-square distribution (Ulm, 1990):
2
2
2
,
2
D
F n
LCL  


2
2
2
1,
1
2
D
F


 
n
UCL
where n is the number of subjects with a specific AE for the incidence rate of interest and is 
the basis for the number of the degrees of freedom for the chi-square quantile for the upper 
tail probability ·2.
The EAER will be the number of AEs including repeat occurrences in individual subjects 
divided by the total time at risk scaled to 100 patient-years and calculated using:
¦
 

 
N
i
i
Risk
AE
T
N
EAER
1
,
100
where NAE is the total number of AEs.
No confidence interval will be computed for EAER.
Where an AE start date is (partially) missing, the AE will be considered TE if possible. 
Imputation rules provided in Section 4.2 are based on the assumption that if the start date is 
incomplete, either day only is missing, or day and months are missing, or date is completely 
missing. Although the algorithms for treatment-emergence depend on the onset date, imputation 
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 88 of 92
rules are provided for resolution date as well, as these may be needed for certain statistical 
analyses, such as an analyses of AE prevalence or AE duration.
Listings based on SS for all AEs will be provided. A glossary for the reported terms will also be
generated utilizing SOC, HLT, and PT.
Anticipated SAEs, as described in Section 10.5 of the clinical study protocol, will not be 
summarized either by any additional tables or listings, as they are included in the standard AE 
summaries.
AEs of interest will be summarized. The following AEs of interest will be summarized in stand-
alone tables:
x
Opportunistic infections
x
Malignant or unspecified tumors
x
Malignant tumors
x
Serious cardiovascular events
x
Demyelinating-like disorders
x
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
x
Serious bleeding events
For the following AEs of interest, no additional tables will be provided, as these are included in 
the standard AE summaries:
x
Serious infections 
x
Congestive heart failure
x
Lupus and lupus-like illness
x
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
The following notes to AEs of interest in the clinical study protocol are given for reporting 
purposes only, and therefore will not be summarized separately: A confirmed LTBI must be 
reported as an AE of interest. Confirmed active TB is an AE of interest. In the event that an 
active TB occurrence meets the protocol’s SAE criteria, it is also an SAE. Potential Hy’s Law, 
defined as ≥3xULN alanine aminotransferase or aspartate aminotransferase with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality is also considered an AE of interest.
The following events are not officially considered to be AEs of interest but are nonetheless 
considered to be interesting enough to be summarized in stand-alone tables:  1) Hepatic events 
and 2) Hypersensitivity reactions and anaphylactic reactions.
The approach for summarizing AEs of interest is detailed in the UCB AE of interest program 
specifications for Cimzia from 18 June 2018.
Data collected on hospitalization will be presented in a listing.
REDACTED
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 89 of 92
Changes in section 10.3:
The changes from Baseline in laboratory evaluations will be analyzed over time in the SS for 
observed cases. Shift tables concerning the normal range at each post-baseline visit, will also be 
produced for each hematology and biochemistry laboratory parameter. The shifts will be 
categorized using L, N, H, missing, and total.
If a repeat sample is taken, the repeated sample data will be used when possible. If the value of a 
parameter collected at the scheduled visit is missing and an additional sample associated with 
this visit is taken before the next scheduled visit, the missing value will be replaced by this value. 
Early Withdrawal Visits will be assigned to what would have been the next scheduled visit. In 
the Urinalysis, microscopy (WBC, RBC, casts, crystals, and bacteria) will be performed only 
when there are abnormalities on the dipstick. This data will be listed and not presented in tables.
Has been changed to:
The changes from Baseline in laboratory evaluations will be analyzed over time in the SS for 
observed cases. Shift tables concerning the normal range at each post-baseline visit, will also be 
produced for each hematology and biochemistry laboratory variable. The shifts will be 
categorized using L, N, H, missing, and total.
If a repeat sample is taken, the repeated sample data will be used when possible. If the value of a 
variable collected at the scheduled visit is missing and an additional sample associated with this 
visit is taken before the next scheduled visit, the missing value will be replaced by this value. 
Early Withdrawal Visits will be assigned to what would have been the next scheduled visit. In 
the Urinalysis, microscopy (WBC, RBC, casts, crystals, and bacteria) will be performed only 
when there are abnormalities on the dipstick. This data will be listed and not presented in tables.
Changes in section 12.1:
Not applicable.
Has been changed to:
12.1       APPENDIX 1: Compliance Ratio Calculation
The general formula for treatment compliance is given as follows:
ܥܴൌ
்ವೠೝ̴ೞ೟ೠషο಴ೠ೘
்ವೠೝ̴ೞ೟ೠ
where TDur_stu is the study duration and 'Cum is the cumulative difference between actual and 
scheduled day of administration. The CRD ranges between 0 and 1.
There are 2 methods to determine the CR. CR(1) is based upon scheduled days which reference 
the Baseline visits. CR(2) is based upon scheduled days which reference the previous dosing 
administration date. CR(1) and CR(2) each will be computed separately. The definition of study 
duration and cumulative difference varies for the 2 calculations. In all cases, if the subject was 
randomized, but study drug was never administered then the CR is equal to 0. The CR is limited 
REDACTED
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 90 of 92
to a range of 0 to 1. Therefore, if for any reason a negative value is computed, the CR must be set 
to 0. Specific details for each calculation follow.
CR(1):
ܶ஽௨௥̴௦௧௨ൌܦܽݐ݁௅௔௦௧െܦܽݐ݁஻௅
ο஼௨௠ൌσ ȁܣܦ௜െܵܦ௜ȁ
௜
where i=Week 0, 2, 4, 6,  … , XX
where ADi = Actual day of administration, for Week i=0 to XX by 2
SDi = (i/2) x 14, 
for Week i=0 to XX by 2
Note: XX represents the last completed visit in which study drug
should have been administered. If subject is still in the study but ADi
is missing, then ABS[ADi – SDi]=14 for the missed Visit i.
CR(2):
ܶ஽௨௥̴௦௧௨ൌܦܽݐ݁௅௔௦௧െܦܽݐ݁஻௅
ο஼௨௠ൌ෍ȁܣܦ௜െܵܦ௜ȁ
௜
where i= Week 0, 2, 4, 6,  … , XX
where ADi = Actual day of administration, for Week i=0 to XX by 2
SDi = {0,
for Week i=0
}
{14 + ADi-2,
for Week i=2 to XX by 2 }
Note: XX represents the last completed visit in which study drug
should have been administered. If subject is still in the study but ADi
is missing, then ABS(ADi – SDi)=14 for the missed Visit i.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 91 of 92
Example
Week
Scheduled
day (1)
Scheduled
day (2)
Actual day
ABS Diff (1)
ABS Diff (2)
0
0
0
0
0
0
2
14
14
13
1
1
4
28
27
29
1
2
6
42
43
-
14
14
8
56
57
55
1
2
10
70
69
69
1
0
Total
-
-
-
18
19
CR
66/84 =0.79
65/84 =0.77
Note that this example is for a 12 week study.
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UCB
21 Feb 2020
Statistical Analysis Plan
Certolizumab pegol
AS0007
Confidential
Page 92 of 92
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution.
COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.