An Open-label, Multicenter Study to Assess the Safety of Certolizumab Pegol in Children and Adolescents With Active Crohn's Disease Who Completed C87035 (NCT00899678) or Who Were Terminated From C87035
Phase: PHASE2
Conditions: Crohn's Disease
Sponsor: UCB Pharma

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 1 of 119
PROTOCOL CR0012
AN OPEN-LABEL, MULTICENTER STUDY TO ASSESS THE 
SAFETY OF CERTOLIZUMAB PEGOL IN CHILDREN AND 
ADOLESCENTS WITH ACTIVE CROHN’S DISEASE WHO 
COMPLETED C87035 OR WERE TERMINATED FROM 
C87035 WHEN THE STUDY WAS STOPPED BY UCB
PHASE 2B
IND Number: 11197
Sponsor:
UCB BIOSCIENCES, INC.
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
Protocol/Amendment Number
Date
Type of amendment
Final Protocol
07 May 2010
N/A
Amendment 1
29 Jun 2010
Substantial
Amendment 2
08 May 2012
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.
REDACTED 
rpor
rpo
h, NC
h, NC
NITE
NITE
RE
COPY 
ES, IN
ES, IN
orat
orat
This document t cannot
s doc
doc
, repr
repr
c
be used 
us
to support 
rt
sup
any marketing 
D
g
ng
ket
m
authorization 
N
te Driv
e Driv
C  276
276
D STA
D ST
application 
NC.
C.
and any extensions or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 2 of 119
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.
EDACTE
TED OPY 
OP
CO
This document cannot be used to support any marketing au
authoriz
n
rization applica
ap
cation 
a
d 
and any
ny 
ions 
ensio
exten
or 
or variations 
v
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 3 of 119
STUDY CONTACT INFORMATION
Sponsor
UCB BIOSCIENCES, INC.
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
Sponsor Study Physician
Name:
, MD
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Clinical Project Manager
Name:
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Clinical Study Biostatistician 
Name:
, PhD
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
REDACTED 
rate Dr
ate Dr
27617
2761
ED
ED
RE
COPY 
CO
This document cannot 
no be 
be used 
se
to support 
st
st
po
up
suppo
any 
ticia
ici
mar
arketing 
tin
ti
arket
authorization 
on
rive
ve
7, USA
, USA
za
a
application 
tio
and 
an
any 
a
extensions 
io
ten
or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 4 of 119
Medical Monitor
Name:
, MD
Address:
5610 Point West Drive
Oakwood, GA 30566
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PRA International
Address:
Glen Lake 6
4130 Parklake Avenue
Raleigh, NC 27612
Phone:
919-786-8200
Fax:
919-786-8201
COPY 
Y
OP
This document cannot be used to support any marketing authorization 
n application 
tio
pli
a
and any 
ny extensions s
xt
or 
o variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 5 of 119
SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h), safety related issues, and emergency 
unblinding
Fax
Europe and Rest of the World (except Japan): +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Phone
During business hours:
Outside business hours:
Europe and Rest of the World 
(except Japan): +32 2 386 24 68
USA & Canada:
+1 770 970 2709
Europe and Rest of the World 
(except Japan): +32 2 386 24 68
USA & Canada:
+1 678 799 4007
REDACTED COPY 
COPY
This document cannot be used to support any marketing authorization 
n application
anad
nad
8 799 4
8 799
and
n):): +3
+3
any 
of the
of th
2
y extensions 
rs:s:
ns
e
or 
or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 6 of 119
TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................10
1
SUMMARY.....................................................................................................................12
2
INTRODUCTION ...........................................................................................................13
3
STUDY OBJECTIVES....................................................................................................14
4
STUDY VARIABLES.....................................................................................................14
4.1
Safety variables......................................................................................................14
4.2
Efficacy variables...................................................................................................15
4.3
Pharmacokinetic and immunological variables .....................................................16
5
STUDY DESIGN.............................................................................................................16
5.1
Study description ...................................................................................................16
5.1.1
Study duration per subject ...........................................................................17
5.1.2
Planned number of subjects and sites ..........................................................17
5.1.3
Anticipated regions and countries................................................................17
5.2
Schedule of study assessments...............................................................................18
5.3
Schematic diagram.................................................................................................22
5.4
Rationale for study design and selection of dose...................................................23
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................23
6.1
Inclusion criteria ....................................................................................................23
6.2
Exclusion criteria ...................................................................................................23
6.3
Withdrawal criteria ................................................................................................23
7
STUDY TREATMENTS.................................................................................................25
7.1
Description of investigational medicinal product(s)..............................................25
7.2
Treatments to be administered...............................................................................25
7.3
Packaging...............................................................................................................27
7.4
Labeling .................................................................................................................27
7.5
Handling and storage requirements .......................................................................27
7.6
Drug accountability................................................................................................28
7.7
Procedures for monitoring subject compliance......................................................28
7.8
Concomitant medication(s)/treatment(s) ...............................................................29
7.8.1
Permitted concomitant treatments (medications and therapies) ..................29
7.8.2
Prohibited concomitant treatments (medications and therapies) .................30
7.8.3
Rescue therapy.............................................................................................30
7.9
Enrollment and numbering of subjects ..................................................................30
8
STUDY PROCEDURES BY VISIT ...............................................................................31
8.1
Entry Week 0 .........................................................................................................31
8.2
Week 2 Visit ..........................................................................................................31
REDACTED
SUB
SUB
.......
....
......
......
....
....
COPY 
......
......
n of d
n of d
BJ
This document cannot 
7.8.1
7.8.1
7
be
Con
Con
used
acco
acco
ocedu
cedu
to 
 an
ou
ou
support 
......
....
.......
.....
nd st
nd st
any 
minis
mini
marketing 
.......
......
........
.....
ational
tiona
t
authorization 
dose
ose
JECT
ECT
......
....
......
.....
application 
........
......
........
......
.......
......
and 
.
......
....
any 
..
.....
...
extensions
........
.........
.......
............
....
.
or 
14
1
1
variations 
4
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 7 of 119
8.3
Phone call (home administration) or visit (clinic administration) (every 4 
weeks and in between regular clinic visits beginning at Week 6).........................32
8.4
Regular clinic visits................................................................................................32
8.4.1
Assessments every 12 weeks beginning at Week 14...................................32
8.4.2
Assessments at Weeks 14, 26, 38, 50 and then every 12 months 
thereafter:.....................................................................................................33
8.5
Completion/Early Termination Visit .....................................................................33
8.6
Reinduction visits...................................................................................................34
8.7
Unscheduled Visit..................................................................................................34
8.8
Safety Follow-Up Visit..........................................................................................35
9
SAFETY ASSESSMENTS..............................................................................................35
9.1
Adverse events.......................................................................................................35
9.1.1
Definition of adverse event..........................................................................35
9.1.2
Procedures for reporting and recording adverse events...............................36
9.1.3
Description of adverse events......................................................................36
9.1.4
Follow-up on adverse events .......................................................................36
9.1.5
Rule for repetition of an adverse event........................................................36
9.1.6
Pregnancy.....................................................................................................37
9.1.7
Overdose of investigational medicinal product ...........................................37
9.1.8
Safety signal detection.................................................................................38
9.2
Serious adverse events...........................................................................................38
9.2.1
Definition of serious adverse event .............................................................38
9.2.2
Procedures for reporting serious adverse events..........................................39
9.2.3
Follow-up of serious adverse events............................................................39
9.3
Adverse events of interest......................................................................................39
9.4
Immediate reporting of adverse events..................................................................40
9.5
Laboratory measurements......................................................................................40
9.6
Other safety measurements....................................................................................41
9.6.1
Demographics ..............................................................................................41
9.6.2
Assessment of childbearing potential ..........................................................41
9.6.3
Pregnancy test..............................................................................................41
9.6.4
Physical examination...................................................................................41
9.6.5
Tuberculin test .............................................................................................41
9.6.5.1
Mantoux tuberculin skin test (PPD test) ............................................41
9.6.6
Evaluation of signs and symptoms of TB....................................................42
9.6.7
Vital signs ....................................................................................................43
9.6.8
Concomitant medications ............................................................................43
9.6.9
Medications for CD .....................................................................................43
REDACTED 
medic
medi
......
......
......
......
us ad
us ad
COPY 
vent
vent.
....
....
This document cannot 
6.3
6.
9.6.
9.6.
be 
3
used
Dem
Dem
A
to
fety
fety
support
orting 
ting
measu
measu
m
any 
nteres
ntere
marketing 
.
dverse 
dverse
orting s
rting 
ious a
ous 
authorization 
.......
.....
cinal p
cinal p
......
....
....
....
application 
ent
............
..
.......
.....
.......
....
and 
........
nts...
ts...
any 
......
.....
.
extensions
......
....
.........
.......
........
.......
or
.34
.34
variations 
3
4
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 8 of 119
9.6.10
Autoantibodies.............................................................................................43
10
EFFICACY ASSESSMENTS .........................................................................................43
10.1
Disease activity/PCDAI.........................................................................................43
10.2
Erythrocyte sedimentation rate ..............................................................................44
10.3
C-reactive protein...................................................................................................44
10.4
Tanner stage...........................................................................................................44
10.4.1
Bone markers ...............................................................................................44
10.5
Height.....................................................................................................................44
10.6
Weight....................................................................................................................45
10.7
IMPACT-III...........................................................................................................45
10.8
Days missed from school/work (WPAI:CD for children and for working 
individuals with CD)..............................................................................................45
10.9
Effect on the caregiver's work (WPAI:CD for caregivers)....................................46
10.10 Concurrent medical procedures .............................................................................46
11
PHARMACOKINETICS AND IMMUNOLOGICAL ASSESSMENTS.......................47
12
STUDY MANAGEMENT AND ADMINISTRATION.................................................47
12.1
Adherence to protocol............................................................................................47
12.2
Monitoring .............................................................................................................47
12.2.1
Definition of source data..............................................................................47
12.2.2
Source data verification ...............................................................................48
12.3
Data handling.........................................................................................................48
12.3.1
Case report form completion .......................................................................48
12.3.2
Database entry and reconciliation................................................................48
12.3.3
Subject Entry and Enrollment log/Subject Identification Code list.............49
12.4
Termination of the study........................................................................................49
12.5
Archiving and data retention..................................................................................49
12.6
Audit and inspection ..............................................................................................50
12.7
Good Clinical Practice...........................................................................................50
13
STATISTICS ...................................................................................................................50
13.1
Definition of analysis sets......................................................................................50
13.2
General statistical considerations...........................................................................51
13.3
Planned safety analyses..........................................................................................51
13.4
Planned efficacy analyses ......................................................................................52
13.5
Pharmacokinetics and immunological analyses.....................................................53
13.6
Handling of protocol deviations.............................................................................53
13.7
Handling of dropouts or missing data....................................................................53
13.8
Planned interim analysis and data monitoring.......................................................54
13.9
Determination of sample size.................................................................................54
....
......
......
........
......
......
.....
mp
m
COPY 
TIO
I
..........
...
....
This document 
1
cannot
G
3.3
3.3
13
13
be 
Defef
Ge
Ge
used 
ICS
CS
fini
fin
to
inic
inic
support 
data r
data r
inspect
nspect
al
any 
nd
stud
study
marketing 
....
pletion
pletion
d recon
recon
d Enr
d En
authorization 
.
.......
......
......
.....
.........
.......
....
application 
......
ESS
SSM
.......
.....
.....
.....
and 
.......
...
.
any
.......
.....
extensions 
...
........
........
............
....
rking
king
or 
..44
.44
variations 
44
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 9 of 119
14
ETHICS AND REGULATORY REQUIREMENTS......................................................54
14.1
Informed consent ...................................................................................................54
14.2
Subject identification cards....................................................................................55
14.3
Institutional Review Boards and Independent Ethics Committees........................55
14.4
Subject privacy.......................................................................................................56
14.5
Protocol amendments.............................................................................................56
15
FINANCE, INSURANCE, AND PUBLICATION.........................................................56
16
REFERENCES ................................................................................................................56
17
APPENDICES .................................................................................................................58
17.1
Tuberculosis questionnaire ....................................................................................58
17.2
Pediatric Crohn’s Disease Activity Index..............................................................59
17.3
IMPACT III ...........................................................................................................72
17.4
Work Productivity and Activity Impairment Questionnaire for children with 
CD (WPAI:CD for children)..................................................................................80
17.5
Work Productivity and Activity Impairment Questionnaire for working 
individuals with CD (WPAI:CD for working individuals with CD).....................82
17.6
Work Productivity and Activity Impairment Questionnaire for caregivers of 
children with CD (WPAI:CD for caregivers of children with CD).......................84
17.7
Protocol amendment #1 .........................................................................................86
17.8
Protocol Amendment 2 ..........................................................................................89
18
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................119
LIST OF TABLES
Table 5-1. Schedule of study assessments .............................................................................18
Table 7-1. Doses of CZP in CR0012 .....................................................................................26
LIST OF FIGURES
Figure 5-1: Schematic Diagram...............................................................................................22
REDACTED 
......
......
......
....
URE O
URE 
IST
IST
COPY 
g
ent Qu
ent Q
givers 
ivers
This document cannot be used to support 
Diagram
iagra
any
001
00
L
marketing 
T OF 
T OF
sments
men
12
12
authorization
s of ch
of c
......
.....
......
......
OF IN
OF IN
application 
......
nnaire 
naire
viduals
idual
uestion
estio
hih
and
for ch
or c
.
any 
.......
.....
hi
extensions 
...
........
........
.........
.......
.......
......
or 
..56
.56
variations 
56
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 10 of 119
LIST OF ABBREVIATIONS
AE
adverse event
ANA
antinuclear antibody
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CDP870
certolizumab pegol
CI
confidence interval
CDMS
clinical data management system
CRF
Case Report Form
CRO
contract research organization
CRP
C-reactive protein
CZP
certolizumab pegol
dsDNA
double-stranded deoxyribonucleic acid
DSMB
Data and Safety Monitoring Board
ELISA
enzyme-linked immunosorbent assay
ESR
erythrocyte sedimentation rate
ET
Early Termination
EU
European Union
Fab′
antigen-binding fragment
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilance
HIPAA
Health Insurance Portability and Accountability Act
HRQOL
health-related quality of life
IBD
inflammatory bowel disease
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IMP
investigational medicinal product
INH
isonicotinic acid hydrazide (isoniazid)
IRB
Institutional Review Board
REDACTED
ring B
ring 
unosor
noso
menta
menta
tion
tion
COPY 
ucleic 
clei
B
This document 
C
IEC
IEC
cannot 
H
be used to
G
suppor
and 
and
Good C
ood 
Glo
Gl
any
ndin
ndi
d D
d D
marketing 
n
ion
on
ing
ing
authorization 
ac
ac
Board
oard
orbent 
rbent 
tion r
on r
application 
cidid
and any extensions or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 11 of 119
ITT
Intention-To-Treat
iv
intravenous
IVRS
Interactive Voice Response System
MedDRA®
Medical Dictionary for Regulatory Activities®
PCDAI
Pediatric Crohn’s Disease Activity Index
PEG
polyethylene glycol
PFS
prefilled syringe
PK
pharmacokinetics
PPD
purified protein derivatives
PT
Preferred Term
Q2W
every 2 weeks
Q4W
every 4 weeks
QFT-GOLD
QuantiFERON®-TB GOLD
RBC
red blood cell
SAE
serious adverse event
SAP
Statistical Analysis Plan
sc
subcutaneous
SD
standard deviation
SFU
Safety Follow-Up
SOC
System Organ Class
SOP
Standard Operating Procedures
TB
tuberculosis
TNF
human tumor necrosis factor alpha
US
United States
WBC
white blood cell
WPAI:CD
Work Productivity and Activity Impairment Questionnaire for CD
WHODrg
World Heath Organization Drug
lan
lan
tion
tion
COPY 
This document cannot 
:CD
CD
HOD
HOD
be used to 
h
support
dard 
ard 
bercul
bercu
hum
hu
any
rgan
ga
d Op
d O
marketing 
Up
Up
an C
an
authorization application and any extensions or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 12 of 119
1
SUMMARY
This is a Phase 2b, open-label, multicenter study to assess the safety of certolizumab pegol 
(CDP870, CZP) in children and adolescents with active Crohn’s disease (CD) who completed 
C87035 or were terminated from C87035 when the study was stopped by UCB. 
C87035 was a Phase 2, open-label, multicenter study to assess the safety, efficacy, 
pharmacokinetics (PK), and immunogenicity of CZP in children and adolescents ages 6 to 17 
with moderately to severely active Crohn’s disease. The study was performed as a 
postapproval commitment following the Food and Drug Administration (FDA) approval of 
CZP for the treatment of adults with moderately to severely active CD.
 the decision was made to stop C87035 after determining it was 
inadequate to address the efficacy of CZP for labeling in pediatric subjects. Subjects ongoing 
in the study were given the opportunity to enter CR0012 without having completed C87035.
Certolizumab pegol, the investigational medicinal product (IMP) is a humanized antibody 
fragment antigen binding (Fab′), with specificity for human tumor necrosis factor alpha 
(TNF), conjugated to polyethylene glycol (PEG). The drug intended for use in this study is 
the liquid formulation of CZP in a prefilled syringe (PFS).
All subjects who complete Week 62 of C87035 or were terminated from C87035 when the 
study was stopped by UCB (and completed all assessments required for Week 62/Visit 23 at 
the time of termination) are eligible to enter this open-label extension study. 
Following entry, subjects may continue on the CZP dose they were receiving at the end of 
C87035 (Low-Dose Group or High-Dose Group [weight adjusted in kg]) every 4 weeks 
(Q4W). The first clinic visit of this study should coincide with the last visit of C87035
(Week 62/Visit 23). Home administration of CZP by the subject/caregiver/appropriate 
designee as determined by the Investigator will be permitted following appropriate training at 
clinic visits. For subjects performing home administration, a phone call to the subject and/or 
the parents/caregiver will be performed by the Investigator (or designee) every 4 weeks 
between regular clinic visits. A Safety Follow-Up (SFU) Visit will be conducted 12 weeks 
after the last dose of study medication.
If a subject has not been previously reinduced in C87035, the subject is eligible for 
1 reinduction due to loss of response in CR0012 (defined as an increase in Pediatric Crohn’s 
Disease Activity Index [PCDAI] ≥15 points compared to Week 6 of C87035 at 2 consecutive 
visits at least 1 week apart or an overall PCDAI >30 points at any time).
A Data and Safety Monitoring Board (DSMB) will periodically review all emerging safety 
data.
The primary objective of the study is to assess the longterm safety and tolerability of CZP in 
children and adolescents with moderately to severely active CD. As secondary objectives, 
this study further assesses the longterm efficacy, PK, and immunogenicity of CZP treatment 
in this population. 
REDACTED 
asse
asse
this op
this op
on the 
on the
ose G
ose G
tudy
tudy
COPY 
FS)
FS
were t
were
essm
ess
This document 
The 
The 
ch
ch
cannot 
a and
and
a.
be
vi
st 1 
st 1 
used
ue to 
e to 
ityty I
y
to
been
bee
support 
pe
p
its.
ts. A 
A 
udy
dy me
m
y
n p
any
ming
min
erform
erform
marketing 
Gro
ro
y shoul
shou
y
ation of
tion o
estigato
stiga
g h
g
authorization 
term
er
ments
ments
pen
en-lala
e CZP 
CZP 
oup 
up 
application
necro
necr
nded f
nded 
rmin
min
and 
huma
huma
any 
ubj
ub
omple
mple
exten
ining 
ning 
bjec
bjec
ions 
oval of
val of
ensio
or 
17
variations 
7
thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 13 of 119
Safety variables to be evaluated are adverse events (AEs), laboratory parameters 
(hematology, biochemistry, urinalysis), vital signs, and autoantibodies (anti-nuclear antibody 
[ANA] and anti-double-stranded deoxyribonucleic acid [dsDNA] antibody).
The main efficacy variable is the proportion of subjects in clinical remission.
Other efficacy variables include: absolute score and change in PCDAI scores, proportion of 
subjects maintaining clinical response, absolute and change in both C-reactive protein (CRP) 
and erythrocyte sedimentation rate (ESR), and change in growth scores (Tanner stage), 
absolute and change in bone marker values, absolute and change in IMPACT-III scores, days 
missed from school/work, absolute and change in Work Productivity and Activity 
Impairment Questionnaire for CD (WPAI:CD) scores, and concurrent medical procedures 
required during the study.
Pharmacokinetic and immunological variables include measurement of plasma concentrations 
of CZP and detection of anti-CZP antibodies.
2
INTRODUCTION
Tumor necrosis factor alpha is a key proinflammatory cytokine with a central role in the 
immune response. In CD, TNF activates similar processes, with gut epithelial tissue injury 
resulting from induction of proteases, prostaglandins, leukotrienes, eicosanoids, and other 
products, some of which (eg, prostaglandin E2) may also directly cause diarrhea by 
promoting mucosal secretion of chloride and potassium. In addition, both intestinal and 
peripheral phagocytes from subjects with active CD have the capacity to secrete increased 
amounts of TNF.
Several large double-blind, randomized clinical studies of biological products targeted at 
neutralizing TNF have demonstrated marked clinical benefit in subjects with active CD 
(Targan et al, 1997; Rutgeerts et al, 1999; Sandborn et al, 2001). Furthermore, it has been 
shown that sustained clinical benefit over a year can be achieved in subjects who respond to a 
first dose of anti-TNF therapy (Hanauer et al, 2002).
Several TNF-antagonists (including CZP [Cimzia®], adalimumab [Humira®], and infliximab 
[Remicade®]) have been approved for the treatment of CD.
Use of anti-TNF agents has been studied in pediatric patients suffering from CD. Infliximab 
has been approved in the United States (US) and the European Union (EU) for pediatric use 
(Hyams J et al, 2007) and adalimumab is currently under investigation in this population.
It is widely recognized that there exists an unmet need for new therapies for children and 
adolescents with active CD. The primary goal of treatment is to provide longterm reduction 
or remission in the signs and symptoms of their disease. 
Certolizumab pegol is an engineered, humanized antigen-binding fragment (Fab' fragment) 
conjugated to PEG with specificity for human TNF. Certolizumab pegol (CIMZIA) has been 
approved in the US, Switzerland, Russia, Brazil, and Chile for reducing the signs and 
symptoms of CD and maintaining the clinical response in adult subjects with moderately to 
severely active disease who have had an inadequate response to conventional therapy.
REDACTED 
tas
tas
ive CD
ive CD
ed clin
ed clin
mar
mar
COPY
leuk
leuk
ay
ay also
als
y
ssiu
ssiu
This document
Certo
Certo
con
con
cannot
y
ents 
ents 
missio
missio
l
be
y reco
y rec
used
d inin
, 2007
2007
to 
ents
in th
n th
suppor
nclud
clu
approv
appr
ts has
ha
any
Hana
Han
udin
udi
marketing 
nicic
arked c
rked c
999; Sa
999; S
fit over
t ove
naue
nau
authorization 
o did
um. I
m. In
D hav
D hav
cal s
al s
application 
with a c
ith a 
th gut e
th gut
otrienes
riene
direc
irec
and any 
ma a
extensions 
edures
dure
a con
co
or 
ays 
ays
variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 14 of 119
Single intravenous (iv) and subcutaneous (sc) doses of CZP in healthy volunteers have been 
shown to have a predictable dose-related response with an approximately linear relationship 
between the dose administered and the maximum serum concentration (Cmax) and the area 
under the CZP plasma concentration versus time curve (AUC). The terminal elimination 
phase half-life (t1/2) was approximately 14 days for all dosage levels tested and the 
bioavailability of CZP when administered subcutaneously was approximately 80%. A similar 
PK profile was found in healthy Japanese and Caucasian subjects. The metabolism and route 
of excretion of CZP have not yet been fully elucidated.
The safety of CZP has been assessed in 2518 adult subjects with CD representing over 
2837 patient years of exposure. Certolizumab pegol is well tolerated. The incidence of 
injection site reactions and hypersensitivity-type reactions was low. There were no reports of 
anaphylaxis or anaphylactoid-type reactions with CZP. All available data in CD show the 
safety of CZP is consistent with the known risks of anti-TNF therapies.
The risks of the present study are essentially those of experiencing an adverse effect 
following administration of CZP and for loss of response. As a therapeutic class, currently 
available TNF-antagonists are known to be associated with serious infections, particularly 
reactivation of tuberculosis (TB) and opportunistic fungal infections. An association has also 
been reported with TNF-antagonist therapy and the development of lymphoma and leukemia 
especially in children and adolescents, although it is not clear whether there is a causal 
relationship as confounding factors exist (eg, the increased risk of lymphoma and leukemia 
associated with autoimmune diseases and immunosuppression) themselves. Other cancer 
types also have been reported in association with TNF-antagonist use, but the causal 
relationship for these is unclear as well. Other serious AEs that have been infrequently 
reported in subjects treated with currently available TNF-antagonists (including CZP) include 
congestive heart failure, drug-induced lupus, new-onset psoriasis, seizures, demyelinating 
disorders, and pancytopenia.
For more information, please refer to the Investigator’s Brochure.
3
STUDY OBJECTIVES
The primary objective of this open-label, multicenter study is to assess the longterm safety 
and tolerability of CZP in children and adolescents with moderately to severely active CD 
who completed C87035 or were terminated from C87035 when the study was stopped by 
UCB. The secondary objectives of this study are to assess the longterm efficacy, PK, and 
immunogenicity of CZP treatment on this population.
4
STUDY VARIABLES
4.1
Safety variables
•
AEs
•
Laboratory parameters (hematology, biochemistry, urinalysis)
•
Vital signs
•
Autoantibodies (ANA and anti-dsDNA antibody)
REDACTED
munos
muno
n with
n with
Other 
Other
ently
ently a
y
d lu
d lu
COPY 
velo
ve
 not c
not c
ncrea
ncrea
This document 
•
A
cannot be 
ci
used
87
87
ndary
ndary
ty o
y o
to
7035
035
support 
BJ
BJ
f this o
this 
P in ch
P in c
any 
r r 
JEC
JEC
marketing 
ava
va
upus, n
pus, n
to th
to th
authorization
ased r
ased r
uppre
uppre
h TNF
TNF
r serio
serio
ailab
ilab
application
p
s infe
s infe
tions. A
ions.
ment of
ment o
ear wh
ear w
i
and 
dver
ver
eutic 
eutic 
any 
rse e
rse
extensions 
of 
of 
o repo
repo
D show
show
or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 15 of 119
4.2
Efficacy variables
Main efficacy variable:
•
Proportion of subjects in clinical remission (clinical remission is defined as a PCDAI 
score ≤10)
Other efficacy variables:
•
Disease activity variables:
−
Absolute PCDAI scores
−
Change from Baseline (Week 0 of C87035) in PCDAI scores
−
Proportion of subjects maintaining clinical response (clinical response is defined as a 
decrease from Baseline (Week 0 of C87035) in PCDAI score of ≥15 points and a total 
PCDAI score ≤30 points)
−
CRP levels
−
Change from Baseline (Week 0 of C87035) in CRP levels
−
ESR values
−
Change from Baseline (Week 0 of C87035) in ESR values
−
Change from Baseline (Week 0 of C87035) in growth scores (Tanner stage [assessing 
puberty])
−
Bone marker values
−
Changes from Baseline (Week 0 of C87035) in bone marker values
•
Subject-reported outcome variables:
−
Absolute IMPACT-III scores
−
Change from Baseline (Week 0 of C87035) in IMPACT-III score
−
Actual scores of WPAI:CD for children and for working individuals with CD
−
Change from Baseline (Week 0 of C87035) in scores of WPAI:CD for children and 
for working individuals with CD)
−
Concurrent medical procedures
•
Caregiver-reported outcome variables:
−
Actual scores of WPAI:CD for caregivers
−
Change from Baseline (Week 0 of C87035) in scores of WPAI:CD for caregivers
REDACTED 
35
87035
87035
COPY 
5) in 
) in 
This document cannot 
on
on
Care
Care
be 
ncurr
ncur
used
from 
om
rking
rking
to 
o
B
support 
eline (W
line 
of WP
f WP
any 
score
score
marketing 
0 of C
0 of C
ables:
ables
authorization 
ESR 
ESR 
5) in g
) in g
application 
vels
vels
and any
5 poin
5 poi
extensions 
is de
s de
or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 16 of 119
4.3
Pharmacokinetic and immunological variables
•
Plasma concentrations of CZP
•
Detection of anti-CZP antibodies
5
STUDY DESIGN
5.1
Study description
This is a Phase 2, open-label, multicenter study in children and adolescents with moderately 
to severely active CD who completed C87035, or were terminated from C87035 when the 
study was stopped by UCB, to assess the longterm safety and tolerability of CZP. 
All subjects who complete Week 62 of C87035 or were terminated from C87035 when the 
study was stopped by UCB (and completed all assessments required for Week 62/Visit 23 at 
the time of termination) are eligible for entry.
Subjects may continue on CZP at the dose they were receiving at the end of C87035 (Low-
Dose Group or High-Dose Group [weight adjusted in kg; see Section 7.2 and Table 7-1])
every 4 weeks until the subject reaches the age of 18 years or CZP is approved for use in the 
US by pediatric subjects with CD. The first clinic visit should coincide with the last visit of 
C87035 (Week 62/Visit 23). First study drug administration occurs 2 weeks later (Week 2) 
and subsequent clinic visits for safety and efficacy assessments are scheduled at 12-week 
intervals. After Week 2, subjects or parents/caregivers/appropriate designee as determined by 
the Investigator have the option of home administration of CZP upon appropriate training 
during a previous clinic visit(s) or continuing to have CZP administered every 4 weeks at the 
clinic. For subjects performing home administration, a phone call to the subject and/or the 
parents/caregiver will be performed by the Investigator (or designee) every 4 weeks between 
regular clinic visits in order to capture potential AEs and changes in concomitant 
medications, and to check compliance with home dosing. An SFU Visit will be conducted 
12 weeks after the last dose of study medication for subjects.
Please refer to Study Schedule of Assessments in Section 5.2 for visit-specific procedures and 
to Section 5.3 for a schematic representation of the study.
A DSMB will periodically review all emerging safety data (see Section 13.8). Based on the 
safety data, the DSMB can recommend modifying or stopping the study.
Loss of response/reinduction
•
Subjects who were reinduced in C87035 are not eligible for reinduction in CR0012. 
Should loss of response occur in CR0012, the subject must be withdrawn.
•
If there was no reinduction in C87035, 1 reinduction only is permitted in CR0012. If 
response is lost a second time in CR0012, the subject must be withdrawn.
REDACTED 
acy 
acy
aregiv
aregiv
admini
dmin
inuing
inuing
adm
adm
COPY
t sho
sh
nistrat
nistra
y ass
as
This document
•
cannot
Subje
Subje
Sho
Sh
be
pon
on
used
DSM
DSM
nse
nse
to
dica
dic
B
support
dule o
ule o
ematic
emati
alll
any
study
study
marketing
ministr
nist
y the Inv
the I
ure pote
e po
nce w
nce 
authorization 
tion
ion
sessm
essm
vers/ap
ers/a
istratio
istrati
g to ha
to ha
t
application 
e en
tion
ion 7.7
CZP is
CZP i
ld coin
d co
n oc
n oc
and 
end 
nd 
any
ek 6
ek 6
extensions 
te
n the
n the
35 wh
35 wh
62
or 
ly y
variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 17 of 119
Loss of response, defined as an increase in PCDAI ≥15 points compared to Week 6 of 
C87035 at 2 consecutive visits at least 1 week apart, or an overall PCDAI >30 points at any 
time, will result in reinduction and dosing as follows:
•
The reinduction dose will be adjusted to the subject’s weight: 400mg for subjects ≥40kg 
or 200mg for subjects 20 to <40kg sc Q2W for a total of 3 doses
•
Continue dosing with CZP administered sc Q4W as 400mg for subjects ≥40kg or 200mg 
for subjects 20 to <40kg, regardless of the subject’s previous randomized dose group
Summary of visits related to loss of response
1. Loss of response must be confirmed at a clinic visit where assessments and labs are 
performed to determine PCDAI score. Scores cannot be confirmed until lab results are 
received by central lab a few days after the clinic visit. Once loss of response is 
confirmed, sites must contact the subject to return for the first Reinduction Visit.
2. Reinduction Week 0 - subjects will receive the first dose for reinduction at the clinic.
3. Reinduction Week 2 occurs 2 weeks later for second dose at the clinic.
4. Reinduction Week 4 occurs 2 weeks later for third dose at the clinic.
5. Subject resumes the original schedule of clinic visits after reinduction. The clinic should 
contact the Study Monitor to determine the most appropriate way to resume the original 
schedule of clinic visits.
5.1.1
Study duration per subject
The maximum study duration of CZP treatment may be until the subject reaches the age of 
18 years or CZP is approved for use in the US by pediatric subjects with CD. An SFU visit 
will be conducted 12 weeks following the last dose of study drug.
The end of the study is defined as the date of the last SFU visit of the last subject in the study.
5.1.2
Planned number of subjects and sites
It is anticipated that the approximately 30 to 40 centers which participated in C87035 will 
participate in this study. Those subjects who completed Week 62 of C87035 or were 
terminated from C87035 when the study was stopped by UCB (and completed all 
assessments required for Week 62/Visit 23 at the time of termination) may be enrolled in this 
study.
•
First subject first visit: Jul 2010
•
Last subject first visit: Jun 2012
•
Last subject last visit: to be determined (including the SFU Visit)
5.1.3
Anticipated regions and countries
This study will be conducted in the US, Canada, Australia, and New Zealand.
REDACTED 
ect
ect
reatm
reatm
in the
in the
COPY
sits a
sits a
ost app
ost app
This document 
L
5
cannot 
ast sub
st sub
Las
Las
be
bjec
bjec
used
ired
red
to 
703
0
d fo
d fo
support
pproxi
proxi
y. Thos
 Tho
35 w
35 w
any
ber o
ber 
marketing
e US 
e US 
the las
the la
the dat
he da
authorization
prop
prop
ent m
nt m
b
application 
e clin
cli
he clin
he cli
fter rein
ter re
pria
ri
and
ction
ction
ni
any 
on V
on V
n a
extensions 
arere
esults 
sults
nse is
se is 
V
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 18 of 119
5.2
Schedule of study assessments
Table 5-1.
Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in between 
regular clinic visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Written informed consent
X
Assessment of inclusion/ 
exclusion criteria
X
Demography
X
Life style
C87035
Crohn’s disease history
C87035
Medical and surgical history
C87035
Assessment of childbearing 
potential
C87035
X
X
Pregnancy teste
C87035
X
X
X
Physical examination
C87035
X
X
X
TB test
X
TB questionnaire
X
X
X
X
Tanner stage
C87035
X
X
Height
C87035
X
X
Weight
C87035
X
X
Vital signsf
C87035
X
X
X
X
X
REDACTED 
D
TE
DA
RE
COPY 
PY
C
This document cannot 
C
ot
ann
n
be 
C870
C870
e used 
d
035
035
ed
u
to 
to support 
or
po
up
any 
an marketing 
g
et
m
authorization 
tio
riririz
ori
uth
application 
ek 14
k 14
ca
pp
and 
d
and any 
Ear
Ea
Term
Term
extensions 
ns
mpletio
pletio
te
or variations 
on thereof.
08  M
08  M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 19 of 119
Table 5-1.
Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in between 
regular clinic visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Adverse eventsa
C87035
X
X
X
X
X
X
Concomitant medicationsa
C87035
X
X
X
X
X
X
Concurrent medical procedures
C87035
X
X
X
X
X
X
PCDAI
C87035
X
X
ESR/hematocrit/albumin for 
PCDAI
C87035
X
X
CRP
C87035
X
X
Hematology/chemistry/urinalys
is
C87035
X
X
X
IMPACT III
C87035
Xl
X
WPAI:CDg
C87035
Xl
X
Certolizumab pegol plasma 
concentrationh
C87035
X
X
X
Anti-CZP antibody plasma 
concentrationi
C87035
X
X
X
Autoantibodies (ANA and anti-
dsDNA)
C87035
X
X
X
Bone markers (osteocalcin, 
bone specific alkaline 
phosphatase, n-telopeptides)
C87035
Xl
X
REDACTED 
D
AC
ED
COPY 
Y
CO
C
This document cannot 
nn
nn
nn
nn
be 
C870
C87
used 
5
d
us
to 
to support 
po
po
po
po
p
any 
ny marketing 
ke
ma
authorization 
n
at
ori
th
a
application 
on 
X
at
X
pp
a
and 
and any y extensions 
ion/ 
n/ 
arlyly
minati
inat
io
or r variations 
on
v
thereof.
08  M
08  M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 20 of 119
Table 5-1.
Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in between 
regular clinic visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Study drug administrationj
X
X
X
Reinductionk
Loss of response must be confirmed at a clinic visit where assessments and labs are performed to determine PCDAI score. 
Scores cannot be confirmed until lab results are received by central lab a few days after the clinic visit. Once loss of 
response is confirmed, sites must contact the subject to return for the first Reinduction Visit.
Reinduction Week 0 (first reinduction dose) is followed by Reinduction Week 2 (second dose, 2 weeks after first dose), and 
Reinduction Week 4 (third dose, 2 weeks after second dose). Subjects should return to the clinic for each Reinduction. 
Subject resumes the original schedule of clinic visits after reinduction. The clinic should contact the Study Monitor to 
determine the most appropriate way to resume the original schedule of clinic visits.
Reinduction Week 0 assessments: PCDAI: ESR, hematocrit, and albumin; IMPACT-III; WPAI:CD
Reinduction Week 2 assessments: PCDAI: ESR, hematocrit, and albumin
Reinduction Week 4 assessments: PCDAI: ESR, hematocrit, and albumin; WPAI:CD
ANA=antinuclear antibody; CRP=C-reactive protein; CZP=certolizumab pegol; dsDNA=double-stranded deoxyribonucleic acid (antibody); 
ESR=erythrocyte sedimentation rate; ET=Early Termination; PCDAI=Pediatric Crohn’s Disease Activity Index; SFU=Safety Follow-Up; TB=tuberculosis; 
WPAI:CD=Work Productivity and Activity Impairment Questionnaire for CD
aWeek 0 of CR0012 is equivalent to the last visit (Week 62; status evaluation) of C87035 with the following exceptions: written informed consent, 
assessment of inclusion/exclusion criteria, demography, TB testing, and TB questionnaire. Ongoing AEs and concomitant medications from C87035 will 
continue to be followed in CR0012. Other assessments will be taken from the C87035 database by UCB. Subjects who were terminated from C87035 when 
the study was stopped by UCB completed all assessments required for Week 62/Visit 23 at the time of termination.
bAfter Week 2, subjects or parents/caregivers have the option of home administration of CZP upon appropriate training during a previous clinic visit(s) or 
can continue to have CZP administered every 4 weeks at the clinic. For subjects performing home administration, a phone call to the subject and/or the 
parents/caregiver will be performed by the Investigator (or designee) every 4 weeks between regular clinic visits in order to capture potential AEs and 
changes in concomitant medications, and to check compliance with home dosing. Subjects will have the option to either switch to home dosing or switch 
REDACTED
cond d
cond 
visits a
visits a
me the o
e the 
CDAI: E
CDAI: 
: PCDA
: PCDA
PC
P
COPY
y cent
y cen
eturn fo
eturn
ed by R
ed by 
do
d
This document cannot
nis
ni
formed
ormed
edicati
dicati
be 
/care
car
stere
stere
used 
r as
as
eted all
ed all
regi
reg
to 
emo
mo
sses
sses
support 
inati
nat
ment Q
ment 
it (Wee
Wee
ograp
ogr
any
P=cert
P=cer
tion;
ion
marketing 
AI: E
: E
CDAI: E
DAI: E
ket
authorization
Reindu
Reindu
se). Sub
e). Sub
fter rein
ter rein
original
original
ESR, he
SR, h
ESR
ESR
application 
on 
ts and la
s and l
l lab a fe
lab a f
the fir
the fir
cat
and 
and any y extensions 
ion/ 
n/ 
arlyly
minati
inat
io
or r variations 
on
v
thereof.
08  M
08  M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 21 of 119
Table 5-1.
Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in between 
regular clinic visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
back to site administration at anytime during the study.
cVital signs, concomitant medication, and AEs must be assessed at every Unscheduled Visit. Other safety and PK assessments (eg, CZP plasma sample) may 
be performed at the discretion of the Investigator as related to the nature of the visit.
dThe SFU Visit should be performed 12 weeks after the final dose of study medication. For subjects continuing directly onto commercial CZP, a SFU Visit 
should be completed prior to the first dose of commercial drug administration.
eFor all females post menses, a urine pregnancy test will be conducted at all regularly scheduled clinic visits except Week 2.
fVital signs will be collected 15 minutes prior to dosing with a ±5 minute window.
gDays missed from school will be assessed using the WPAI:CD for children. The time missed from work will be assessed using the WPAI:CD for working 
individuals with CD. The effect of the child’s CD on the caregiver’s productivity will be assessed using the WPAI:CD for caregivers of children with CD.
hPlasma samples will be collected to determine the concentration of CZP every 12 weeks starting at Week 14, and at the Completion/Early Termination and 
SFU Visits. Samples will be collected before dosing (except for the Completion/ET and SFU Visits when there is no dosing).
iAnti-CZP antibody concentrations in plasma will be collected every 12 weeks starting at Week 14, and at the Completion/ET and SFU Visits (anti-CZP 
antibody measurements will be made using the samples taken for PK measurements at these time points, so additional blood draws will not be required).
jIf home administration is performed, sufficient study drug will be dispensed at the scheduled every 12-week clinic visit to last until the next scheduled clinic 
visit.
kIf a subject has not been previously reinduced in C87035, the subject is eligible for 1 reinduction due to loss of response in CR0012.
lMeasured at Weeks 14, 26, 38, 50 and then every 12 months thereafter.
REDACTED 
ll regu
ll regu
ute win
ute win
r childr
r child
er’s
er’s p
COPY 
cation. 
cation
This document cannot be used 
en n
to
n eve
eve
support 
y drug
drug
in C87
in C8
any 
ed
aken fo
aken f
g w
marketing
roduct
roduc
of CZP e
of CZP
r the Co
the C
d ever
eve
authorization 
For 
For
larly sc
arly sc
ndow.
dow.
en. Th
n. Th
application
Other saf
ther sa
r sub
sub
n
on and 
and any y extensions 
ion/ 
n/ 
arlyly
minati
inat
io
or r variations 
on
v
thereof.
08  M
08  M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 22 of 119
5.3
Schematic diagram
Figure 5-1:
Schematic Diagram
CZP=certolizumab pegol; Q4W=every 4 weeks
REDACTED COPY 
This document cannot be 
ry 4
y 4
used 
4 w
4 w
d to support any marketing authorization application and any 
nsions 
extens
or variations 
on thereof.
08  M
08  M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 23 of 119
5.4
Rationale for study design and selection of dose
Following the Food and Drug Administration (FDA) approval of CZP for the treatment of 
CD in adults, C87035 was a postapproval commitment to investigate the administration of 
CZP administration in children and adolescents with moderately to severely active CD. This 
study will provide continued treatment of CZP to subjects who completed C87035 or were 
terminated from C87035 when the study was stopped by UCB and who, in the Investigator’s 
opinion, would benefit from continued administration of CZP.
The primary objective of this open-label study is to assess the longterm safety and tolerability 
of CZP in children and adolescents with moderately to severely active CD who completed 
C87035 or were terminated from C87035 when the study was stopped by UCB. The 
secondary objectives of this study are to assess the longterm efficacy, PK, and 
immunogenicity of CZP treatment on this population. Subjects may continue on CZP at the 
dose they were receiving at the end of C87035.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved 
written Informed Consent form is signed and dated by the subject or by the parent(s) or 
legally acceptable representative. The Consent form or a specific Assent form, where 
required, will be signed and dated by minors.
2. Subject/parent(s)/legally acceptable representative is considered reliable and capable of 
adhering to the protocol, visit schedule or medication intake according to the judgment of 
the Investigator.
3. Subject completed the C87035 study (Week 62 Visit) or was terminated from C87035 
when the study was stopped by UCB and completed all assessments required for 
Week 62/Visit 23 at the time of termination.
4. Subject’s current or recent regimen of concomitant medication(s) for CD should be stable 
through the study period (see Section 7.8.1).
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if the following criterion is met:
1. Subject did not complete the C87035 study (Week 62 Visit) or was terminated from 
C87035 when the study was stopped by UCB but did not complete all assessments 
required for Week 62/Visit 23 at the time of termination.
6.3
Withdrawal criteria
Subjects (or represented by their parent[s]/legally acceptable representative[s]) are free to 
withdraw from the study at any time, without prejudice to their continued care. Whenever 
possible, cases should be discussed with the UCB Study Physician or designee prior to 
withdrawing the subject. All subjects withdrawn due to an AE must be followed until 
resolution of the event or until subject is stable.
REDACTED
nsent 
sent 
minors.
inors.
e repre
e repre
hedule
hedule
COPY 
nt Eth
nt Eth
dated
dated
f
This document 
6.3
6.3
cannot 
ect d
ct d
87035
7035
requi
requi
be 
did
did
used 
xcl
cl
ot pe
ot pe
to 
lus
lus
support 
im
im
recent r
ecent
period
period
any 
by 
by U
me of
me of
marketing
e or m
e or m
study
study
UC
U
authorization
d by
d by thth
y
form o
form o
esenta
senta
application 
criteria
criteri
ics Co
cs Co
h
and
BJE
JE
any 
C
extensions 
eted 
ed 
e
on CZ
n CZ
o
lity
lity
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 24 of 119
The Investigator may withdraw a subject from the study if in the opinion of the Investigator:
•
The subject develops a clinically relevant medical condition that, in the opinion of the 
Investigator, jeopardizes or compromises the subject’s ability to participate in this study.
•
The subject develops an intolerable AE, as determined by the subject and/or Investigator, 
which cannot be controlled by appropriate therapy.
•
The subject fails to comply with the protocol.
•
Other safety issues arise during the course of the study. 
•
Subjects who require any of the following therapies must be withdrawn from study 
participation:
−
Anti-TNF therapy (other than CZP) or any biologic therapy for CD (eg, natalizumab)
−
Immunosuppressants (eg, azathioprine/6-mercaptopurin, or methotrexate)
−
Surgery related to exacerbation of CD (seton insertion per se is not to be considered 
surgery)
−
Inpatient hospitalization for exacerbation of CD
•
The subject becomes pregnant (as evidenced by a positive pregnancy test) or plans to 
become pregnant during the study.
•
The Investigator feels that it is in the subject’s best interest to be withdrawn.
•
Subjects must be withdrawn if requested by the Sponsor or a regulatory agency.
•
Subjects who were reinduced once in C87035 cannot be reinduced in CR0012 and must 
be discontinued from CZP treatment at the time of loss of response.
•
Subjects can undergo only 1 reinduction in this study; if response is lost a second time, 
the subject must be withdrawn from the study (see Section 5.1). 
Any subject withdrawn from the study will be treated at the Investigator’s discretion as per 
standard clinical practice.
Investigators should attempt to obtain information on subjects, in the case of withdrawal or 
discontinuation. For subjects considered as lost to follow-up the Investigator should make an 
effort (at least 1 phone call and 1 written message to the subject), and document his/her effort 
(date and summary of the phone call and copy of the written message in the source 
documents) to complete the final evaluation. All results of these evaluations and 
observations, together with a narrative description of the reason(s) for removing the subject, 
must be recorded in the source documents. The case report form (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.
REDACTED 
ect’s b
ect’s 
sted b
sted b
ce in C
ce in C
COPY 
a posi
a pos
This document
must
must
prim
prim
cannot 
su
su
ments) 
ents) 
ervati
rvati
t b
t b
be 
ast 1
st 
umm
umm
used 
uldld
n. For 
For 
1 p
1 p
o
d att
d att
support 
rom the
om th
ice.
ce.
any
wn fr
wn f
marketing 
C870
C870
nt at the
t at th
inducti
nduc
from
fro
authorization 
best in
best i
y the 
the 
03
03
application 
tive pr
ive p
and 
s not 
not 
any 
rexate
rexat
extensions 
dy
dy
, nata
nata
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 25 of 119
7
STUDY TREATMENTS
7.1
Description of investigational medicinal product(s)
The investigational product will be supplied under the responsibility of the Sponsor. The 
frequency at which the investigational product will be supplied to each individual site will be 
adapted to the availability of the investigational product, and expiry date of the 
investigational product. Study drug will be managed by the Interactive Voice Response 
System (IVRS) in order to ensure all sites have sufficient quantities of study drug available.
Drug supplies will consist of the following (allocated based on dosing Table 7-1):
•
1mL syringes with 25G needles of CZP, containing an injectable volume of 1mL 
(equivalent to a dose of 200mg)
•
0.5mL syringes with 25G needles of CZP, containing an injectable volume of 0.5mL
(equivalent to a dose of 100mg)
Certolizumab pegol (acetate pH 4.7) is an anti-TNF, humanized antibody Fab′ fragment 
conjugated with PEG.
7.2
Treatments to be administered
Details on drug dispensing and administration will be provided in the Pharmacy Manual.
Certolizumab pegol will be administered by the Investigator/designee during clinic visits. 
After Week 2, home administration of CZP by the subject or parent/caregiver/appropriate 
designee as determined by the Investigator will be permitted between scheduled clinic visits. 
Subjects/caregivers who do not choose home administration will continue to have CZP 
administered every 4 weeks at the clinic.
All Investigators and designees will be given instructions on the administration of study drug. 
The PFS should be allowed to reach room temperature for a minimum of 30 minutes before 
injection. The acclimatization time must be followed very strictly. The maximum time for the 
product at room temperature is 2 hours.
Injections will be given sc; suitable areas include upper arm, lateral abdominal wall, and 
upper outer thigh. Each injection should be administered at a separate injection site and a 
rotation between the injection sites should be observed for each injection. Treatment of the 
injection site with an anesthetic cream (containing lidocaine and prilocaine; eg, EMLA®) 
prior to dosing is permissible. Dosing will be administered based on the subject’s weight as 
specified in Table 7-1.
Following study drug administration, the used PFS must be disposed appropriately (eg, using 
a sharps container).
Subjects will be observed for possible AEs for 30 minutes after each dose of study drug (1 or 
2 injections) is administered, whether at clinic visits or at home, and subjects and/or 
parents/caregivers will be asked to contact the Investigator in case any reactions occur within 
the 2 hours following study drug injection.
REDACTED
he Inv
he Inv
P by
by thth
y
ator wi
ator w
se hom
se hom
nic
ni
COPY 
l be p
l be p
This document
ollll
a sha
a sha
S
cannot 
osi
os
ied in
ed in
lowi
owi
be 
e w
sing 
sing 
used 
Ea
E
en the 
n the 
with
with
o
ve
Each
ach
support
on ti
n ti
ture is 2
ure is
n sc; 
n sc; 
i
any
each
each
time
im
marketing
me a
me a
c.
l be giv
be g
r
authorization
provid
provi
vestiga
estiga
he sub
he sub
ill be 
ll be
ad
ad
application
ntibod
ntibo
de
d
and 
d
any
olum
olu
extensions 
f 1mL 
1mL 
ume
me
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 26 of 119
The concentration of CZP is 200mg/mL. Depending on the dose, injections will be given sc 
as 1 or 2 injections of 1mL each resulting in doses of 200 and 400mg, respectively, or as 
1 injection of 0.5mL resulting in a dose of 100mg. To achieve the appropriate doses, 
injections are administered as follows:
For subjects in the High-Dose Group (weight adjusted) CZP 400mg/200mg Q4W:
•
Subjects weighing 20 to <40kg (44 to <88lbs): 1 injection of 1mL
•
Subjects weighing ≥40kg (≥88lbs): 2 injections of 1mL each
For subjects in the Low-Dose Group (weight adjusted) CZP 200mg/100mg CZP Q4W:
•
Subjects weighing 20 to <40kg (44 to <88lbs): 1 injection of 0.5mL
•
Subjects weighing ≥40kg (≥88lbs): 1 injection of 1mL
Dosages and injections needed to achieve this dose are also presented in Table 7-1.
A subject should only change dosing category during the course of the study if his/her weight 
increases by >2kg (4.4lbs) (measured at a clinic visit only) AND crosses the 40kg/88lb 
boundary (eg, a subject’s weight increases from 39 to 41kg (from 85.8 to 90.2lbs). No dose 
adjustment is made for a weight decrease. In the event of a dose increase, the first injection of 
the higher dose must be administered at a clinic visit for all subjects, including those subjects 
performing home administration.
Table 7-1.
Doses of CZP in CR0012
CZP dose (mg) injectionsa
Treatment group
High-Dose Group
Low-Dose Group
Dose frequency
Q4W
Q4W
Subject weight
20 to <40kg (44 to <88lbs)
1x1mL PFS/200mg
1x0.5mL PFS/100mg
≥40kg (≥88lbs)
2x1mL PFS/400mg
1x1mL PFS/200mg
CZP=certolizumab pegol; PFS=prefilled syringe; Q4W=once every 4 weeks
Prior to CZP administration at home, subjects/caregivers/appropriate designee as determined 
by the Investigator will be trained by the site staff and provided written instructions on the 
schedule and fixed dose for injection, and the correct sc injection technique including 0.5ml 
and 1ml injections, as appropriate. Starting at Week 2, subjects/caregivers/appropriate 
designee as determined by the Investigator may administer the study medication under the 
supervision of the site staff to ensure that the study medication is being properly and safely 
injected. Once subjects/caregivers/appropriate designee as determined by the Investigator 
have been trained, the study medication may be administered at home. If administered at 
home, the subject/caregiver/appropriate designee as determined by the Investigator is 
requested to document the container number, date, and time point of administration of study 
REDACTED 
vis
vis
012
12
ED
COPY
41kg
41k
vent o
vent o
isit f
sit
This document 
nd d 
desig
desig
su
su
cannot
nves
nves
dule a
dule a
1m
1m
be
ZP ad
ZP ad
titi
used to
egol;
gol;
support 
8lbs)
lbs)
t
po
PF
P
su
any y
ny
a
marketing 
High
Hig
etin
ar
authorization
f a d
a 
for all
for all
a
application 
of the s
of the
ND cro
ND cr
g (from
(from
dos
dos
and 
inin Ta
Ta
any extensions 
W:
W:
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 27 of 119
medication. All used PFSs will be disposed of by subjects/caregivers/appropriate designee as 
determined by the Investigator in an acceptable disposal (sharps) container directly after the 
administration. The subjects/caregivers return the documentation together with any 
used/unused containers at the next scheduled clinic visit. Subjects who are unable to self̻
administer the study treatment, those without a caregiver who can help, or those who choose 
not to self-inject, will continue to visit the clinic for study treatment administration between 
regular scheduled visits. In addition, subjects will have the option to either switch to home 
dosing or switch back to clinic administration at anytime during the study.
7.3
Packaging
Each site will receive uniquely numbered PFSs. The PFSs will be packaged in individual 
protective containers with a uniquely numbered carton.
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Conference 
on Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good 
Manufacturing Practice and will include any locally required statements. If necessary, labels 
will be translated into the local language.
Each PFS will be inserted into a labeled individual container. Only the tear-off section (left 
section) of the label will be attached to the CRF at the time of administration (or dispensing 
to the subject/caregiver/appropriate designee as determined by the Investigator for home 
administration) to the subject, and the main section which will remain affixed to the 
individual container.
Prefilled syringes used for administration will be labeled with the same unique identifier 
(MED ID) as on the individual container. 
Name, address and phone number of the Investigator will be included on the subject 
identification card (see Section 14.2).
7.5
Handling and storage requirements
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the 
site. Investigational medicinal product stored by the Investigator is to be kept in a secured 
area with limited access. All investigational products must be stored refrigerated at 2 to 8ºC 
(35 to 46°F) and protected from light.
Appropriate storage conditions must be ensured either by controlled room temperature 
(2 to 8ºC [35.6 to 46.4°F]), or by completing a temperature log in accordance with local 
requirements but at least once a day during the business week, with minimum and maximum 
temperatures reached over the time interval.
In case an out-of-range temperature is noted, it must be immediately communicated to the 
Sponsor before further use of the IMP.
The Clinical Project Manager (or designee) will transmit the out-of-range temperature (copy 
of the temperature log, duration of the out-of-range temperature, if available) to the Drug 
Supply Coordinator. Based on discussion with Quality Assurance, the Drug Supply
REDACTED
det
de
section
ection
tion w
tion w
iner
iner
COPY
ntain
ntai
the tim
the ti
eterm
ter
This document 
In ca
In ca
S
cannot
C [35
[35
remen
emen
perat
perat
be
e sto
sto
5 6
5
used
d prot
prot
ora
ora
to
cess
ces
support 
and
n
ignee) 
gnee)
edicin
edicin
s
any 
.
d st
d st
marketing 
will
ill
r. 
f the
the In
I
2).).
authorization
me 
me 
rmined
mined
n whic
whi
l be
be
application
)
ements
ment
er. Onl
r. On
of
of
and
erna
rna
and G
and 
any 
atio
ati
extensions 
vidual
idual
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 28 of 119
Coordinator will then provide the Clinical Project Manager (or designee) with instructions for 
the site regarding use of the IMP.
For IMP dispensed to the subject/caregiver/appropriate designee as determined by the 
Investigator for home dosing, the Investigator (or designee) will instruct the 
subject/caregiver/appropriate designee as determined by the Investigator to store the IMP 
following the instructions on the label. Cooler bags with freezer packs will be provided to 
transport home dosing supplies. 
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.
Copies of completed dispensing records will be collected. Periodically and at the end of the 
study, all unused and expired investigational product (PFSs and container) will be collected 
and sent to the Sponsor (or designee) for destruction. All used PFSs will be disposed of by 
site staff in an acceptable disposal (sharps) container directly after the administration. All 
containers of the used PFSs must be kept until the accountability is checked by the monitor 
and can be destroyed afterwards.
The Investigator (or designee) is responsible for retaining all used and unused containers of 
IMP until returned or destroyed.
For home administration, any used/unused containers should be stored in provided containers 
and returned at the next clinic visit.
The Investigator may assign some of his/her duties for drug accountability at the study site to 
an appropriate pharmacist/designee.
Investigational medicinal product intended for the study cannot be used for any other purpose 
than that described in this protocol. The Investigator must ensure that the IMP is used only in 
accordance with the protocol.
7.7
Procedures for monitoring subject compliance
Subjects are expected to receive all doses of study drug as detailed in the schedule of 
assessments (Section 5.2). Any subject who deviates from the dosing schedule or misses any 
scheduled treatment should be reported to the Medical Monitor for determination of possible 
schedule adjustments and continued eligibility. These instances will be handled on a case-by-
case basis.
At each visit after IMP is dispensed, subjects must return all unused IMP and empty IMP 
containers. Drug accountability must be done in the subject’s presence in order to obtain 
explanations regarding discrepancies in compliance with the dosing regimen. Drug 
accountability must be recorded on the Drug Accountability form.
ble for
ble for
nuse
nuse
COPY 
All u
l
r direc
r direc
acco
acco
This document
case 
ase 
A
cannot 
nts
nts
uled tr
led t
edule 
dule 
b
be 
 ex
ex
s (
s (S
used
Proc
roc
xp
xpec
ec
to 
pr
p
ce
support
produ
rodu
his prot
s pro
rotoc
otoc
any 
gnee.
gnee
marketing
ed con
ed con
of his
of hi
authorization
ountab
unta
r retain
r retain
application
call
cally a
y 
d contai
conta
ed PFSs
d PFS
tlyly aft
af
y
bi
and any 
ate
ate
the st
the s
extensions 
mation 
mation 
stud
study
he stu
e stu
e fo
e fo
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 29 of 119
If a subject is found to be persistently noncompliant (missing 2 or more consecutive 
scheduled IMP doses or missing 3 or more doses), the Sponsor in conjunction with the 
Investigator will make a decision as to whether the subject should be withdrawn from the 
study.
7.8
Concomitant medication(s)/treatment(s)
The subject must not participate in any other clinical study or receive any unauthorized 
medication during the study period.
Should any treatment other than the investigational product be used, including 
over-the-counter products, an accurate record must be kept in the clinic chart (source 
documentation) and the CRF. This record should include the name of the drug, the dose, the 
date(s) of administration, and the indication for use.
7.8.1
Permitted concomitant treatments (medications and therapies)
Subjects should keep concomitant medications for CD (eg, aminosalicylates) stable through 
the study period. 
Topical hydrocortisone for skin disorders or not more than 800μg per day inhaled 
beclomethasone, or equivalent, for asthma are permitted.
Subjects who use antidiarrheals on an as-needed basis should continue their use as required 
and at the usual dose.
Shortterm antibiotic use for the treatment of acute infections is permitted during the study. 
Oral contraceptive use should continue at a stable medication and dose, if already used at 
C87035 entry. If a subject becomes sexually active during the study, acceptable methods of 
birth control (eg, oral contraceptives) should be employed.
If a subject experiences a concomitant illness requiring pain relief (eg, headache) during the 
course of the study, non-narcotic opiate analgesia (eg, ibuprofen) is recommended.
Subjects should not receive any live or attenuated vaccination during the study, or within 
3 months after last dose of study drug. If a subject is scheduled for vaccination during the 
study, the Investigator must contact UCB or its representative to discuss the type of 
vaccination planned.
Treatment of the injection site with an anesthetic cream (containing lidocaine and prilocaine; 
eg, EMLA®) prior to dosing is permissible. Its use will be recorded as concomitant 
medication on the CRF.
Tuberculosis prophylactic treatment should be captured in the concomitant medication page 
of the CRF.
Other concomitant medications and doses for conditions other than CD may be adjusted as 
clinically appropriate during the study period. Any changes in concomitant medications must 
be recorded in the CRF.
REDACTED 
acute 
acute 
at a sta
at a sta
exuall
exuall
sh
sh
COPY 
d.d.
sis sho
sis s
This document 
Othe
Othe
clc
cannot 
n
rculos
culos
he CR
he C
be
 p
on t
on t
used
e inje
e inje
prior 
rior
to 
d.
support 
any
f study
f stud
must c
must 
any 
op
op
y liv
y li
marketing
ly a
y
hould b
ould b
ant illn
nt illn
piate
piat
authorization 
ou
 infec
infec
able m
ble m
acti
act
application 
μg per d
g per
uld co
ld co
and
ylates
late
any
d the
d th
s)
extensions 
e dose
dose
he
h
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 30 of 119
7.8.2
Prohibited concomitant treatments (medications and therapies)
Use of corticosteroids or corticotrophins for indications other than CD is not permitted. 
However, topical hydrocortisone for skin disorders or not more than 800μg per day inhaled 
beclomethasone, or equivalent, for asthma is permitted.
Concomitant use of the following immunosuppressants is not permitted:
•
Azathioprine, 6-mercaptopurine, or methotrexate
•
Mycophenolate or thalidomide
•
Cyclosporine or tacrolimus
Use of any experimental unregistered therapy or biological therapy (within or outside a 
clinical study) or participation in any clinical study using nonbiological therapies is not 
permitted.
7.8.3
Rescue therapy
Subjects who require the following defined rescue therapy to treat an exacerbation of CD at 
any time during the study will be treated as treatment failures from and including the time of 
receiving rescue therapy. For the purpose of this study, the defined rescue therapy which 
would classify the subject as treatment failure is as follows:
•
Anti-TNF therapy (other than CZP) or any biologic therapy for CD (eg, natalizumab)
•
Immunosuppressants (eg, azathioprine/6-mercaptopurin, or methotrexate)
•
Surgery related to exacerbation of CD (seton insertion per se is not to be considered 
surgery)
•
Inpatient hospitalization for exacerbation of CD
•
Increase of corticosteroid dose above Week 0 of C87035 levels as defined below:
−
For subjects not taking corticosteroids at Week 0 of C87035
◦
Any dose ≥10mg/day prednisone (or equivalent) is considered rescue therapy
−
For subjects taking corticosteroids at Week 0 of C87035
◦
Any increase ≥50% of the Week 0 dose is considered rescue therapy
◦
OR
◦
Any dose >40mg/day prednisone (or equivalent) is considered rescue therapy
7.9
Enrollment and numbering of subjects
To enroll a subject, the Investigator must contact the IVRS. Subjects will retain the unique 
subject number allocated in C87035. This unique subject number will be required in all 
communications between the Investigator (or designee) and the IVRS regarding a particular 
subject. The IVRS will allocate container numbers to the subjects based on the unique subject 
REDACTED
y biolo
biol
e/6-
/6-me
me
f CD (
f CD (
COPY
y, the
, th
s follo
s follo
This document 
7.9
7.9
T
cannot 
◦
A
be 
OR
OR
used 
y inc
inc
y
r
to
tak
tak
support
ing c
ng c
10mg/d
0mg
ini
any
se a
se a
cor
marketing 
(set
set
cerbati
erbat
abo
ab
authorization 
ows:
ws:
ogic th
ogic th
ercapt
ercapt
eton
ton
application 
at an ex
t an e
from a
from 
define
defin
and any
apie
api
extensions 
outsid
utsid
es
es
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 31 of 119
number during the course of the study. Subject numbers and container numbers will be 
tracked via the IVRS and also will be required to be entered into the CRF.
The IVRS will allocate containers of study medication as appropriate to the visit schedule. 
8
STUDY PROCEDURES BY VISIT
During the study, the acceptable window between the study visits is +/-7 days relative to 
entry (Week 0).
8.1
Entry Week 0 
Week 0 of CR0012 is equivalent to Week 62 of C87035 with the exceptions noted below. 
Subjects who were terminated from C87035 when the study was stopped by UCB completed 
all assessments required for Week 62/Visit 23 at the time of termination.
Before any study-related procedures are performed, an IRB/IEC approved informed consent 
will be properly executed and documented. The written informed consent of the child’s 
parent(s)/legally acceptable representative(s) must be obtained. In addition, where requested 
by local laws or by the IRB/IEC and according to the child’s age/competence, the Assent 
form should be obtained from the child. The subjects and their parent(s)/legally acceptable 
representative(s) 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 and their parent(s)/legally acceptable representative(s) will be given the 
opportunity to ask the Investigator any questions regarding potential risks and benefits of 
participation in the study.
Assessments to be performed include:
•
Written informed consent
•
Inclusion/ exclusion criteria
•
Demography
•
TB test
•
TB questionnaire
The following ongoing information must be continued to be followed from C87035 to 
CR0012:
•
Adverse events
•
Concomitant medications
8.2
Week 2 Visit
•
Vital signs
•
Adverse events
•
Concomitant medications
REDACTED
ons re
ons re
COPY 
er a
r 
As pa
As pa
eptab
eptab
This document 
8.2
8.2
cannot 
rse
s
oncom
nco
be 
e ev
e ev
used
ngoin
goi
to 
ng
support any marketing authorization
ble rep
le re
gardin
ardin
application
ompe
omp
parent(
arent
y inform
infor
rt of th
t of t
and 
nt o
t o
dition,
ition
any
nform
nfor
of th
of th
extensions 
elow. 
low. 
comp
comp
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 32 of 119
•
Concurrent medical procedures
•
Study drug administration (including training and self-injection under supervision, as 
appropriate)
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing
8.3
Phone call (home administration) or visit (clinic 
administration) (every 4 weeks and in between regular clinic 
visits beginning at Week 6)
After Week 2, subjects and/or parents/caregivers have the option of home administration of 
CZP upon appropriate training during a previous clinic visit(s) or can continue to have CZP 
administered every 4 weeks at the clinic. For subjects performing home administration, a 
phone call to the subject and/or the parents/caregiver will be performed by the Investigator 
(or designee) every 4 weeks between regular clinic visits. Subjects will have the option to 
either switch to home dosing or switch back to site administration at anytime during the 
study.
Assessments performed during the phone call or at the clinic visit include:
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
Study drug administration (check for compliance)
8.4
Regular clinic visits 
8.4.1
Assessments every 12 weeks beginning at Week 14
•
Assessment of childbearing potential (female subjects only)
•
Urine pregnancy test (female subjects of childbearing potential only)
•
Physical examination
•
TB questionnaire
•
Tanner stage
•
Weight and height
•
Vital signs
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
PCDAI
REDACTED 
for com
or co
COPY 
This document 
•
A
cannot
ight a
ght a
Vital
Vital
be
stag
ag
used
naire
aire
ge
ge
to 
ati
support 
ng
(fema
(fema
ion
on
any 
g pote
g pote
marketing 
its 
ts 
ery 1
ery 
authorization 
mplian
plian
application 
an
visit in
visit in
and
hav
hav
nytytim
i
any 
the I
he In
ve th
ve
extensions 
ration
ation
o have
have
istrat
strat
or 
c 
c 
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 33 of 119
•
ESR/hematocrit/albumin for PCDAI
•
CRP
•
Hematology, clinical chemistry, and urinalysis
•
Certolizumab pegol plasma concentration
•
Anti-CZP antibody plasma concentration
•
Autoantibody concentrations (ANA and anti-dsDNA)
•
Study drug administration (including training and self-injection under supervision, as 
appropriate)
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing
8.4.2
Assessments at Weeks 14, 26, 38, 50 and then every 12 months 
thereafter:
•
IMPACT III
•
WPAI:CD (for children, for working individuals with CD, and for caregivers)
•
Bone markers (osteocalcin, bone specific alkaline phosphatase, n-telopeptides)
8.5
Completion/Early Termination Visit
•
Assessment of childbearing potential (female subjects only)
•
Urine pregnancy test (female subjects of childbearing potential only)
•
Physical examination
•
TB questionnaire
•
Tanner stage
•
Weight and height
•
Vital signs
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
PCDAI
•
ESR/hematocrit/albumin for PCDAI
•
CRP
•
Hematology, clinical chemistry, and urinalysis
•
IMPACT III
•
WPAI:CD (for children, for working individuals with CD, and for caregivers)
REDACTED
atio
atio
femal
femal
ects of
ects of
COPY 
ithth
ne ph
ne ph
on
This document
E
•
cannot 
urr
ur
CDA
CDA
ES
ES
be 
rent
rent
used 
s
ant m
nt m
to support any marketing 
f c
authorization 
hosp
osp
n Vis
Vis
le subj
e subj
child
child
application 
D, and f
and
sphat
pha
and 
ver
e
any 
ry 1
ry
extensions 
as
as
by
by thth
y
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 34 of 119
•
Certolizumab pegol plasma concentration
•
Anti-CZP antibody plasma concentration
•
Autoantibody concentrations (ANA and anti-dsDNA)
•
Bone markers (osteocalcin, bone specific alkaline phosphatase, n-telopeptides)
8.6
Reinduction visits
Loss of response must be confirmed at a clinic visit where assessments and labs are 
performed to determine PCDAI score. Scores cannot be confirmed until lab results are 
received by central lab a few days after the clinic visit. Once loss of response is confirmed, 
sites must contact the subject to return for the first Reinduction Visit.
Reinduction Week 0 assessments:
•
PCDAI (using the ESR, hematocrit, and albumin results of the same visit)
•
ESR, hematocrit, and albumin 
•
IMPACT-III
•
WPAI:CD for children and/or WPAI:CD for working individuals
•
WPAI:CD for caregivers of children with CD
Reinduction Week 2 assessments: 
•
PCDAI (using the ESR, hematocrit, and albumin results of the same visit)
•
ESR, hematocrit, and albumin
Reinduction Week 4 assessments: 
•
PCDAI (using the ESR, hematocrit, and albumin results of the same visit)
•
ESR, hematocrit, and albumin
•
WPAI:CD for children and/or WPAI:CD for working individuals
•
WPAI:CD for caregivers of children with CD
•
Study drug administration will be performed at the clinic for all Reinduction injections 
(Weeks 0, 2, and 4). Subject resumes original schedule of clinic visits after reinduction. 
The clinic should contact the Study Monitor to determine the most appropriate way to 
resume the original schedule of clinic visits.
8.7
Unscheduled Visit
•
Vital signs
•
Adverse events
REDACTED 
D
rit, and
it, and
COPY
rking 
king
This document
rere
8
annot
dy dr
 dr
y
Weeks
Weeks
The 
The
be 
ru
ru
used 
for ca
for ca
to
hild
hild
support
hem
hem
nd albu
d alb
dren
any 
:
mat
ma
marketing 
d alal
authorization 
albu
lbu
application 
ndivid
ndivi
and
e vis
vis
any 
sit)
it
extensions 
e
nfirme
nfirme
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 35 of 119
•
Concomitant medications
•
Concurrent medical procedures
Other safety and PK assessments (eg, CZP plasma sample) may be performed at the 
discretion of the Investigator as related to the nature of the visit.
8.8
Safety Follow-Up Visit
The SFU Visit is to be completed by all subjects 12 weeks after the final dose of study 
medication. For subjects who continue directly onto commercial CZP, a SFU Visit should be 
completed prior to the first dose of commercial drug administration.
•
Urine pregnancy test (female subjects of childbearing potential only)
•
Physical examination
•
TB questionnaire
•
Vital signs
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
Hematology, clinical chemistry, and urinalysis
•
Certolizumab pegol plasma concentration
•
Anti-CZP antibody plasma concentration
•
Autoantibody concentrations (ANA and anti-dsDNA)
9
SAFETY ASSESSMENTS
9.1
Adverse events
Adverse event information (duration, intensity, relationship to study drug, action taken, 
outcome, and seriousness will be recorded) will be obtained by observation and direct 
questioning of the subject and his/her parent(s)/legally acceptable representative(s), eg, “have 
you had any (other) medical problems since your last visit?” or “have you felt different in any 
way since your last visit?” 
Ongoing AEs from C87035 will continue to be followed in CR0012. Adverse events will be 
assessed taken throughout the course of the study will be collected at every visit, phone 
contacts, and Unscheduled Visits.
9.1.1
Definition of adverse event
An adverse event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product which does not necessarily have 
a causal relationship with this treatment. An AE can therefore be any unfavorable and 
REDACTED 
nal
nalys
ysisis
ration
ration
ntrat
ntrat
COPY 
This document
se
conta
conta
9
cannot 
y
oing A
ing A
essed
ssed
be 
(o
(
your
your
used
ou
ou
the su
he su
othe
othe
to
usne
usne
support 
even
eve
ation 
tion 
any
SSES
SE
marketing 
tion
tion
NA and
NA an
authorization 
s
application and any extensions
uld b
uld 
or 
be
be
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 36 of 119
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.
In order to ensure complete safety data collection, all AEs occurring during the study 
(ie, after signing the Informed Consent form), including any pretreatment and posttreatment 
periods required by the protocol, must be reported in the CRF even if no investigational 
product was taken but specific study procedures were conducted. This includes all AEs not 
present prior to the initial visit and all AEs which recurred or worsened after the initial visit.
Signs or symptoms of the condition/disease for which the investigational product 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 (Week 0 of 
C87035).
9.1.2
Procedures for reporting and recording adverse events
Besides the Investigator’s observations, 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 employed in the 
study.
9.1.3
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) 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 
study medication) are described in the CRF completion guidelines.
9.1.4
Follow-up on 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 still ongoing at the end of the study for a subject, follow-up should be provided 
until resolution/stable level of sequelae, 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
12 weeks after the subject has discontinued their IMP. 
9.1.5
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:
REDACTED
self
elf
se eve
se eve
ator s
ator s
COPY 
your 
ou
f a
This document
igni
gni
Inve
Inve
1
cannot
E is s
E is s
l resol
reso
nific
ific
be
that
that
used 
l
be fo
be fo
t it
t it
to 
ow
ow
support 
the Ad
the A
describ
escrib
u
any 
, d
, d
menta
menta
marketing
should
houl
han rec
han re
nsisten
nsiste
diary
diar
authorization 
he
assessm
ssess
ents
ents
d
application
he op
e op
h study
study
ealth
alth
and
e ev
e ev
pp
any 
en
extensions 
ing
ng
o the c
the c
riod (W
od (
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 37 of 119
•
The outcome date of the first AE that is not related to the natural course of the disease 
being the same as the start date of the repeated AE, and the outcome of “worsening”, 
•
The AE verbatim term being the same for the first and repeated AE, so that the repeated 
AE can be easily identified as the worsening of the first one. 
9.1.6
Pregnancy
Should a subject become pregnant after the first intake of any IMP, UCB’s Global Clinical 
Safety and Pharmacovigilance (GCSP) department should be informed immediately. The 
subject should be withdrawn from the study as soon as pregnancy is known and the following 
should be completed:
•
The subject should return for an early discontinuation visit.
•
The subject should immediately stop the intake of the investigational medicinal 
product or be down-titrated as instructed at the early discontinuation visit. 
•
An SFU Visit should be scheduled 12 weeks after the subject has discontinued their 
IMP.
The Investigator must inform the subject of information currently known about potential risks 
and about available treatment alternatives.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, 
UCB will ask the Investigator or designee to contact the subject and his partner to request 
consent via the Partner Pregnancy Consent form. If the partner agrees to provide additional 
information, the Pregnancy Report and Outcome form will be forwarded to the subject’s 
partner for completion.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to 
the Investigator. The progression of the pregnancy and the eventual birth (if applicable) must 
be followed-up using the Pregnancy Report and Outcome form in which the Investigator has 
to report on the health of the mother and of the child. The health of the child must be 
followed 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.
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion, or anomaly/birth defect of the child. Those SAEs must be additionally 
reported using the Investigator SAE Report form.
9.1.7
Overdose of investigational medicinal product
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be 
recorded in the CRF. Any SAE or nonserious AE associated with excessive dosing must be 
followed as any other serious or nonserious AE. These events may be symptomatic, in that 
the excessive dosing results in clinical signs and symptoms, or the excessive intake may itself 
be a symptom.
rolle
rolle
o conta
o conta
nt form
t for
d Outc
d Outc
COPY
on cu
on c
ed
ed
This document
Exce
Exce
rec
rec
cannot
d usin
usin
7
be
e, ab
e, ab
ng
ng
used 
becom
ecom
to 
nc
support 
e mo
mo
r birth 
birth
es, U
es, U
any
ancy
ancy
mothe
oth
marketing 
co
on the P
n the 
of the p
f the
R
authorization 
in a c
n a c
act the
ct the
m. If t
m. If t
ome f
me 
application 
rentl
ently y
and 
has di
as di
any 
me
m
n visi
n vis
extensions 
ow
medi
edi
or
wing
ing
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 38 of 119
9.1.8
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 GCSP 
representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (examples: 
AEs, vital signs, laboratory or electrocardiogram [ECG] results) for which data will be 
periodically reviewed during the course of the study.
Refer to Section 13.8 for details on the DSMB used in this study. 
9.2
Serious adverse events
9.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:
•
Death
•
Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred
in a more severe form.)
•
Significant or persistent disability/incapacity
•
Congenital anomaly/birth defect (including that occurring in a fetus)
•
Important medical event that, based upon appropriate medical judgment, may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one 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, infections that require treatment with parenteral antibiotics, or 
the development of drug dependency or drug abuse.)
•
Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if 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]).
REDACTED 
eaction
action
/in
/in
COPY
wing
win
This document
(A
(
t
cannot
al in
l in
(A
be 
lop
np
np
used
n e
n e
ospital
spital
pme
pme
to
eme
eme
support 
d m
ted in 
ed in
l even
 eve
any
t, ba
t, ba
may
may r
y
marketing 
ncapaci
capaci
t (inclu
(incl
ase
authorization 
n that 
n that 
application 
iousne
iousn
criteria
riteri
and any extensions 
ples:
ples:
ll be
l be
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 39 of 119
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 criterion. 
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.)
9.2.2
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 numbers for SAE reporting listed in the SAE Reporting section at the 
front of the protocol). The Investigator must forward to UCB (or its representative) a duly 
completed Investigator 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.
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 
investigational product), up to 12 weeks from the end of the study for each subject, and to 
also inform participating subjects of the need to inform the Investigator of any SAE within 
this period. Serious adverse events that the Investigator thinks may be associated with the 
investigational product must be reported to UCB regardless of the time between the event and 
the end of the study.
Upon receipt of the SAE form, UCB will perform an assessment of expectedness of the 
reported SAE .The assessment of the expectedness of the SAE is based on the Investigator’s 
Brochure.
9.2.3
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 GCSP 
database without limitation of time.
9.3
Adverse events of interest
An AE of special interest is any AE which is listed in the European Risk Management Plan, 
or meets another commitment requiring nonstandard expedited reporting, even if the AE does 
the 
the 
mation
mation
port fo
port fo
sted t
sted t
COPY 
rep
repor
o
l
This document
Infor
for
da
da
cannot 
AE sho
E sho
ermin
rmin
be
F
used 
he a
e a
F
to 
SA
asse
asse
support
st be 
be
AE fo
AE fo
any
ents th
ents t
e re
e re
marketing 
to co
o co
ertain th
rtain th
eeks fro
eks fr
of the 
of the
h
authorization
rts) re
rts) r
ocal la
cal la
n inclu
inclu
orm.
m.
oll
oll
application 
se.
se.
stigato
stigat
ec
and 
data
dat
onclu
onclu
any
ntativ
ntati
ta ar
ta a
extensions 
nform
nform
g sect
sect
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 40 of 119
not fulfill the expedited reporting criteria of “serious”, “unexpected”, and “associated with 
the use of the drug.” Adverse events of special interest include:
•
Serious infections including opportunistic infections
•
Malignancies including lymphoma 
•
Congestive heart failure
•
Demylinating-like disorders
•
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
•
Serious bleeding events
•
Lupus and lupus-like illness
•
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
9.4
Immediate reporting of adverse events
The following AEs must be reported immediately:
•
SAE: AE that the Investigator classifies as serious by the above definitions regardless of 
causality
•
Suspected transmission of an infectious agent via a medicinal product
•
AE of interest (see Section 9.3)
9.5
Laboratory measurements
Hematology assessments will include the following parameters: red blood cell (RBC) count, 
hemoglobin, hematocrit, platelets, white blood cell (WBC) count, neutrophils, lymphocytes, 
monocytes, eosinophils, and basophils.
Clinical chemistry assessments will include the following parameters: Sodium, potassium, 
total calcium, glucose, creatinine, urea, total protein, albumin, alkaline phosphatase, gamma 
glutamyl aminotransferase (GGT), aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), and bilirubin.
For urinalysis, urine protein and blood will be measured by the dipstick method. If positive, 
microscopic assessments will be done for WBC, RBC, and casts and microbiological culture 
will be undertaken.
Hematology, clinical chemistry, and urinalysis parameters will be assessed at entry Week 0, 
every 12 weeks starting at Week 14, and at the Completion/Early Termination (ET) and SFU 
Visits.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
REDACTED 
agent 
agent 
COPY 
ous by
us b
This document
Hem
em
eve
eve
V
cannot
opic
pic
e und
und
mato
mato
be
sis, u
is, 
c a
c a
used
n
se (AL
e (AL
ur
ur
to
sfer
sfer
support 
ba
ba
sments
ment
, creat
crea
any
ts, w
ts, w
asoph
asop
marketing 
remen
eme
ude the
de th
whi
authorization 
y th
y
via a 
via a 
application 
he ab
he ab
and any
necr
necr
extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 41 of 119
For subjects undergoing reinduction, the parameters ESR, hematocrit, and albumin will be 
measured at Reinduction Weeks 0, 2, and 4.
9.6
Other safety measurements
9.6.1
Demographics
Demographics (date of birth, sex, and race) will be recorded at entry Week 0.
9.6.2
Assessment of childbearing potential
For female subjects, childbearing potential will be assessed every 12 weeks starting at 
Week 14, and at the Completion /Early Termination Visits. 
9.6.3
Pregnancy test
For female subjects of childbearing potential, urine pregnancy tests will be performed every 
12 weeks starting at Week 14, and at the Completion/ET and SFU Visits. 
9.6.4
Physical examination
General appearance, ears, nose, throat, eyes, hair and skin, respiratory, cardiovascular, 
gastrointestinal, musculoskeletal, hepatic, neurological, and mental status will be assessed. 
Abnormalities will be recorded as an AE. Physical examination assessments will be 
performed every 12 weeks starting at Week 14, and at the Completion /ET and SFU Visits. 
9.6.5
Tuberculin test
All sites may use either the purified protein derivatives (PPD) skin test or 
QuantiFERON®-TB GOLD test. Use of QFT-GOLD is acceptable provided the site has 
experience in organizing the QFT-GOLD testing; either the central laboratory or a local 
laboratory may be used. The test will be performed at entry Week 0.
Subjects who experience close contact with an individual with active TB during the conduct 
of the study must be referred to a physician specializing in TB to perform additional 
evaluations to exclude latent/active TB before subject may resume study treatment. Subjects 
who prematurely discontinue treatment for latent TB or who are noncompliant with 
prophylactic therapy must immediately discontinue further administration of study drug but 
need to complete the ET/SFU Visits.
9.6.5.1
Mantoux tuberculin skin test (PPD test)
A Mantoux tuberculin skin test (PPD test) will be performed following the instructions 
below. Multiple puncture tests like the Tine and Heaf tests are not acceptable methods of 
testing because the amount of tuberculin injected intradermally cannot be precisely 
controlled.
The intradermal injection of a measured amount of tuberculin is the standard method of 
detecting infection with Mycobacterium tuberculosis. One-tenth milliliter of PPD 
(5 TU PPD-S or 2TU of PPD-RT 23, as recommended by the World Health Organization) is 
injected into the inner surface of the forearm. Other areas may be used, but the forearm is 
preferred. The use of a skin area free of lesions and away from veins is recommended. The 
injection is made using a one-quarter- to one-half-inch (1cm), 27-gauge needle and a 
tuberculin syringe. The tuberculin should be injected by a qualified health care worker just 
REDACTED 
deriva
deriva
QFT-
QFT-G
OLD te
OLD te
be 
be 
COPY 
mi
m
at the
at the
This document
The i
he i
det
det
(
cannot
becau
becau
olled
olled
i
be
ltiple
ltipl
used 
ant
nt
bercu
bercu
to 
ntou
tou
support
ue tre
e tr
st imm
t imm
ET/SFU
T/SFU
any 
p
tive
ive T
reat
rea
marketing 
ests
perfor
perfor
act with
ct wit
phys
ysici
authorization 
atives
atives
GOLD
GOLD
ting
ing
application
tory
tory, c
,
ntal sta
ntal s
ion ass
on as
Comp
Comp
and any extensions 
form
form
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 42 of 119
beneath the surface of the skin, with the needle bevel upward. A discrete, pale elevation of 
the skin (a wheal) 6 to 10mm in diameter should be produced when the injection is done 
correctly. If it is recognized that the first test was improperly administered, another test dose 
can be given at once, selecting a site several centimeters away from the original injection. A 
note in the record should indicate the site chosen for the second test. Study subject should be 
instructed not to scratch the site and to avoid covering the area with a bandage.
Tests should be read by a trained health care worker between 48 and 72 hours after injection. 
Reading should be performed in good light, with the forearm slightly flexed at the elbow. The 
basis of reading is the presence or absence of induration, which may be determined by
inspection (from a side view against the light as well as by direct light) and by palpation. The 
diameter of induration should be measured transversely to the long axis of the forearm and 
recorded in millimeters even those classified as negative. Erythema should not be measured. 
Subjects should never be allowed to read their own tuberculin skin tests. If a subject fails to 
return within 72 hours to have the PPD skin test read, an ELISA-based assay, such as 
QFT-GOLD, must be performed.
An induration of ≥5mm in response to the intradermal tuberculin skin test is considered to be 
a positive result and evidence for either latent or active TB.
In most countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised subjects, and this definition is to be applied here. The 
purpose of using this conservative definition of positivity is to maximize the likelihood of 
detecting latent TB.
9.6.6
Evaluation of signs and symptoms of TB
Signs and symptoms of TB will be evaluated for all subjects using the questionnaire 
"evaluation of signs and symptoms of tuberculosis" provided in Section 17.1. This 
questionnaire should be used as a source document. The questionnaire will assist with the 
identification of subjects who may require prophylactic therapy for TB. A subject who 
answers “Yes” to the question 
 
” is required to begin 
prophylactic treatment for latent TB. A “Yes” response to 1 or more of the other questions 
within the questionnaire should trigger further careful assessment of risk to determine if 
prophylactic or curative treatment for TB is required. 
All subjects considered at high risk for TB infection will receive prophylactic TB treatment 
(eg, isonicotinic acid hydrazide [isoniazid; INH] therapy for 9 months [with vitamin B6]).
Subjects who do not initiate prophylactic treatment for latent TB per Sponsor requirement, 
prematurely discontinue prophylactic treatment for latent TB or are noncompliant with 
antituberculosis therapy, in the Investigator's opinion, must discontinue further use of study 
medication and be immediately withdrawn from study participation. Once withdrawn from 
study treatment, subjects should return for the ET Visit and complete all early withdrawal 
assessments, and complete a final SFU Visit 12 weeks after the last dose of study medication.
If active TB is suspected or confirmed, the subject must be withdrawn immediately from the 
study and discontinue study medication. The subject must return for the ET Visit and 
complete all early withdrawal assessments, and complete a final SFU Visit 12 weeks after the 
REDACTED 
pos
po
nd sy
nd sy
valuat
valuat
t
COPY
f posi
pos
is d
is defi
e
ositiv
sit
This document 
ntitu
tit
med
med
stst
cannot
s wh
s wh
mature
ature
tube
ube
be
tinic
ni
used 
onsider
nsider
ic a
ic a
to
ative
ative
suppor
or laten
r late
re sho
re sho
e t
ort any
y
any 
an marketing 
ted fo
ed f
ubercu
bercu
urce do
urce d
requi
requ
m
authorization
finit
nit
ivity
vity isi
y
ympto
mpto
for
for
application
kin te
kin t
ivity
vity fo
f
y
ition
tion
and any
sub
su
ay
ay, su
, su
extensions 
ion. T
ion. T
earm a
arm a
be me
e me
ubje
bje
or 
he
h
variations 
he
thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 43 of 119
last dose of study medication. Confirmed active TB is an SAE and must be captured on an 
SAE Report Form and provided to the Sponsor in accordance with SAE reporting 
requirements. As with all SAEs, periodic follow-up reports should be completed as per 
protocol requirement until such time as the TB infection resolves. 
Follow-up information of the suspected or confirmed TB should be provided to UCB at least 
after 3, 9, and 12 months of start date of anti-TB treatment, including hematological and 
biochemical safety parameters, x-ray evolution, and TB diagnosis procedures used to follow 
up and confirm recovery of TB.
9.6.7
Vital signs
Systolic and diastolic blood pressure and pulse rate will be measured 15 minutes prior to 
dosing (with a ±5 minutes window) in a sitting position at entry Week 0, Visit 2, every 
12 weeks starting at Week 14, and at the Completion/ET, Unscheduled, and SFU Visits.
9.6.8
Concomitant medications
Details of all concomitant medications taken throughout the course of the study will be 
collected at every visit, phone contacts, and Unscheduled Visits. Ongoing concomitant 
medications from C87035 will continue to be followed in CR0012.
9.6.9
Medications for CD
Details of medication taken for the treatment of CD will be recorded throughout the study at 
scheduled site visits and via phone calls by the Investigator (designee) at every 4 week 
intervals between regular visits. In addition, information on medication taken as maintenance 
treatment for CD will be recorded throughout the study.
9.6.10
Autoantibodies
Autoantibody (ANA and anti-dsDNA) titers will be determined every 12 weeks starting at 
Week 14, and at the Completion/ET and SFU Visits. 
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
10
EFFICACY ASSESSMENTS
10.1
Disease activity/PCDAI
The subjects’ disease activity will be assessed using the PCDAI. The PCDAI was developed 
by pediatric inflammatory bowel disease (IBD) experts and was validated at 12 North 
American institutions (Hyams et al, 1991). It is a modification of the Clinical Disease 
Activity Index (CDAI) which is the accepted instrument to measure CD disease activity in 
clinical studies with adults. The PCDAI consists of 4 domains (laboratory, height/weight, 
examination, and history) with several assessments that are converted into a PCDAI score 
which can range from 0 to 100 points with a higher score indicating more severe disease 
activity. In comparison to the CDAI, the PCDAI decreases the weighting given to subjective 
historical terms, adds height velocity, and adds ESR to the laboratory measures included 
(Hyams et al, 1991; Otley et al, 1999). The PCDAI is provided in Section 17.2.
REDACTED
C
e Inve
e Inv
n, infor
, info
ghout 
ghout 
COPY 
D wi
D wi
This document
n
exam
exam
wh
wh
cannot
an in
n in
vityty I
y n
ical 
cal 
be
c inf
c inf
nst
nst
used 
se
se
diseas
disea
fla
fl
to
eas
eas
support 
his st
is s
CACY
CY
e
any
ollect
ollec
tud
t
marketing 
A) titers
) titer
T and 
T and
authorization
ill be 
ill be 
estigat
estigat
rmatio
rmatio
t the st
the st
application
of 
Ongoin
Ongoi
012.
012.
and 
f the 
the 
any 
SF
extensions 
rior to
ior to
2, ever
 ever
FU V
U
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 44 of 119
The Investigator will calculate the subjects’ PCDAI scores every 12 weeks starting at 
Week 14, and at the Completion/ET Visit. Calculation of PCDAI scores is also necessary to 
determine whether a subject loses response (Section 5.1). For subjects undergoing 
reinduction, PCDAI scores will be calculated at Reinduction Weeks 0, 2, and 4.
For the calculation of the PCDAI score at a particular visit (to assess efficacy of CZP 
treatment), values for hematocrit, ESR, and albumin are used from the same clinic visit. 
Thus, the PCDAI score calculation cannot be completed until the laboratory values have been 
received at the site. 
Since portions of the PCDAI calculations are based upon a 1-week (7-day) history recall of 
symptoms, subjects and/or caregivers will be contacted prior to the visit with a reminder that 
this information needs to be provided at the visit.
10.2
Erythrocyte sedimentation rate
The ESR will be assessed every 12 weeks starting at Week 14, and at the Completion/ET 
Visit. Results of these measurements form part of the PCDAI assessments described in 
Section 10.1. 
For subjects undergoing reinduction, ESR will be assessed at Reinduction Weeks 0, 2, and 4.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
10.3
C-reactive protein
Levels of CRP will be assessed every 12 weeks starting at Week 14, and at the 
Completion/ET Visit. 
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
10.4
Tanner stage
Assessments of subjects’ developmental stages will be performed to determine the subjects’ 
Tanner stages (Marshall and Tanner, 1969; Marshall and Tanner, 1970). These assessments 
will be performed every 12 weeks starting at Week 14, and at the Completion/ET Visit. 
10.4.1
Bone markers
Markers of bone and collagen turnover, reflecting the childhood growth curve, will be 
measured at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and at the 
Completion/ET Visit. These markers will include: osteocalcin, bone specific alkaline 
phosphatase, and n-telopeptides. Tests will be performed by a central laboratory facility.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
10.5
Height
Height will be recorded every 12 weeks starting at Week 14, and at the Completion/ET Visit. 
Height will be recorded after the shoes have been removed. Height should preferably be 
REDACTED 
weeks
week
on
on
COPY
storag
stora
This document
nstru
nstru
the 
the 
canno
tion/
on/
phatas
hatas
ruc
ruc
be
t We
W
/E
/E
used 
n
ne an
ne an
ee
to
e m
e m
support 
velo
velo
and Ta
nd T
ry 12
12
y
w
any 
lopm
opm
marketing 
, proce
proce
authorization 
s start
start
application 
Reindu
Reindu
ge, and
e, an
and 
e C
ments d
ents d
any 
Comp
Com
extensions
ll of
l of
inder t
nder 
or 
f
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 45 of 119
measured with a wall-mounted stedometer. Results of these measurements form part of the 
PCDAI assessments described in Section 10.1.
10.6
Weight
Weight will be recorded after removal of shoes and heavy clothing. Weight will be measured 
every 12 weeks starting at Week 14, and at the Completion/ET Visit. 
Results of the weight measurement will be used to determine the subject’s CZP dose as 
specified in Table 7-1. In addition, results of these measurements form part of the PCDAI 
assessments described in Section 10.1.
10.7
IMPACT-III
The IMPACT questionnaire is a disease-specific health-related quality of life (HRQOL) 
questionnaire for use in children with IBD that was originally developed and validated by a 
Canadian team (Griffiths et al, 1999; Otley et al, 2002). The IMPACT-III, a modified version 
of the original questionnaire, contains 35 questions assessing the following 6 domains: bowel 
symptoms, systemic symptoms, emotional functioning, social functioning, body image, and 
treatment/interventions. For each question, there are 5 Likert response options. Total 
IMPACT-III scores range from 35 to 185 with higher scores indicating better HRQOL. This 
questionnaire will be used to assess HRQOL of all subjects; however, it has only been 
validated for children aged ≥10 years in North America. The IMPACT-III questionnaire is 
provided in Section 17.3. The IMPACT-III questionnaire will be administered at Weeks 14, 
26, 38, 50 and then every 12 months thereafter, and at the Completion /ET Visit. 
For subjects undergoing reinduction, the IMPACT-III questionnaire will be administered at 
Reinduction Week 0.
The IMPACT-III questionnaire is a copyright of the Pediatric Inflammatory Bowel Disease 
Working Group on Quality of Life (copyright 2002). The IMPACT-III has been provided 
under licences, by the Pediatric Inflammatory Bowel Disease Working Group and must not 
be copied, distributed, or used in any way without prior written permission by the Pediatric 
Inflammatory Bowel Disease Working Group.
10.8
Days missed from school/work (WPAI:CD for children and for 
working individuals with CD)
The Work Productivity and Activity Impairment Questionnaire for children with CD 
(WPAI:CD) is used to
 
 If a subject has left school and is working, the WPAI:CD for 
working individuals is used instead of the WPAI:CD for children. If a subject is both 
attending school and working, both the WPAI:CD for children and the WPAI:CD for 
working individuals are used.
The WPAI:CD for children questionnaire contains 6 questions: 
 
 
 
 
, all 6 questions are completed, and 
 
REDACTED 
stio
stio
erer, and
, and
IMPA
IMPA
COPY
bject
bjec
erica
rica
onn
onn
This document
work
ork
Th
Th
m
cannot
g ind
g ind
nding 
ding 
kin
kin
t
e
is
be used
uctivi
ctiv
s use
use
u
to 
kin
kin
support
se W
e W
misse
miss
ng i
ng
any 
in an
in any
Wor
Wo
marketing 
pyri
yright 
ght
cop
opyri
yr
flamm
lamm
authorization 
Th
Th
naire w
aire w
d at th
d at th
ACT-
CT-I
application 
ion
on
ponse o
onse
ndicatin
ndicat
; howe
how
he IM
he IM
and
wing 
wing 
ning
ing
any 
va
va
a mo
a mod
6
extensions 
HRQO
RQO
alid
alid
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 46 of 119
, the subject completes only question number 6 to 
 
. The 6 items are regrouped into 4 dimensions and the 
scores are expressed as percentages, with higher numbers indicating greater impairment and 
less productivity (Reilly et al, 2008).
The WPAI:CD for working individuals questionnaire contains 6 questions:
 
 
 
 
The WPAI:CD for children questionnaire is administered to all subjects or the 
parent(s)/legally acceptable representative(s) and the WPAI:CD for working individuals 
questionnaire is only administered to subjects who work, under supervision of the 
Investigator or designee at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and at 
the Completion /ET Visit. 
For subjects undergoing reinduction, the WPAI:CD questionnaires will be administered at 
Reinduction Weeks 0 and 4.
The WPAI:CD questionnaire for children with CD (Section 17.4 ) and the WPAI:CD for 
working individuals are provided (Section 17.5).
10.9
Effect on the caregiver's work (WPAI:CD for caregivers)
The WPAI:CD questionnaire for caregivers of children with CD is used to
 
 
he questionnaire contains 6 questions: 
 
 
all 6 questions are completed, and if 
, the caregiver completes only question number 6 to 
reflect 
. The 6 items are regrouped into 4 dimensions and 
the scores are expressed as percentages, with higher numbers indicating greater impairment 
and less productivity.
The questionnaire is administered under supervision of the Investigator or designee to the 
caregiver at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and at the 
Completion/ET Visit.
For subjects undergoing reinduction, the WPAI:CD questionnaire will be administered at 
Reinduction Weeks 0 and 4.
The WPAI:CD questionnaire for caregivers of children with CD is provided in Section 17.6.
10.10
Concurrent medical procedures
Any concurrent medical procedures will be recorded throughout the course of the study at 
every visit, phone contacts, and Unscheduled Visits. 
CTED 
wo
wo
of chi
of ch
DACT
REDA
RE
COPY 
tit
ork 
ork
This document
Rein
ein
Th
T
cannot
etion/
tion/
subje
subje
d
be
t We
We
used
vity
ity
aire 
aire 
to 
ssed
se
y
sup
ed as
d a
t
port 
suppo
ny 
any
a
g
ting 
rketin
mark
m
orization 
(WP
(WP
ildren
ldren
uthor
aut
application 
will
wil
7.4
7.4 ) a
)
and 
ll be
l b
any 
here
her
extensions 
ividua
vidua
the
the
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 47 of 119
11
PHARMACOKINETICS AND IMMUNOLOGICAL 
ASSESSMENTS
Blood samples will be collected to determine plasma concentrations of CZP and anti-CZP 
antibodies every 12 weeks starting at Week 14, and at the Completion/ET and SFU Visits. 
All of these blood draws will be performed prior to study drug administration (except for the 
Completion/ET and SFU Visits when there is no dosing) and all of them coincide with the 
blood collection times for the assessment of hematology and clinical chemistry parameters, 
so that no additional blood sampling is required at these visits. 
Time and date of each blood draw will be documented on the CRF.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
12
STUDY MANAGEMENT AND ADMINISTRATION 
12.1
Adherence to protocol
The Investigator should not deviate from the protocol. In medical emergencies, the 
Investigator may use his/her medical judgment and may remove a study participant from 
immediate hazard before notifying UCB (or its representative) and the IRB/IEC in writing 
regarding the type of emergency and the course of action taken.
12.2
Monitoring
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring Standard 
Operating Procedures (SOPs), ICH-GCP guidelines, 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 contract research organization (CRO) or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all 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.
12.2.1
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 
REDACTED 
to mee
o mee
P guid
P guid
nduct
nduct
ctct
COPY
en
entat
ta
action 
ctio
This document
2.2
2.2
Al
Al
cannot
ocol r
col 
g fulfi
fulfi
2 1
2 1
be
e pro
e pro
used
ource
urce
Mo
Monito
nito
to
ll al
ll al
e d
support
related
elate
llow
llo
any 
visi
vis
stigato
stigat
d
marketing
t, and
an
resear
resear
re expe
e exp
sits t
its
authorization 
ta
et the 
et the 
delines
elines
nd
nd
application
emerg
emer
ve a stu
ve a st
ve) and
e) an
aken.
aken
and any
ION
ION
extensions 
provi
provi
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 48 of 119
recorded. These may include hospital/clinic/general practitioner records, charts, diaries, 
x-rays, laboratory results, printouts, pharmacy records, care records, ECG or other printouts, 
completed scales, or Quality of Life Questionnaires, for example. Source documents should 
be kept in a secure, limited access area.
The following data will be recorded directly in the CRF and will not appear in a source 
document as defined above: IMPACT-III and WPAI:CD.
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and 
dated by the Investigator and become a permanent part of the subject’s source documents. 
The Investigator will authorize the monitor to compare the content of the printout and the 
data stored in the computer to ensure all data are consistent.
Electronic data records such as holter monitor records or electroencephalogram records must 
be saved and stored as instructed by UCB (or designee).
12.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During 
monitoring visits reported data are reviewed with regard to being accurate, complete, and 
verifiable from source documents (eg, subject files, recordings from automated instruments, 
tracings [ECG], x-ray films, laboratory notes). All data reported on the CRF should be 
supported by source documents, unless otherwise specified in Section 13.2.1.
12.3
Data handling
12.3.1
Case report form completion
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in 
the CRFs and in all required reports. 
Any change or correction to the CRF should be dated, initialed, and explained (if necessary) 
and should not obscure the original entry. Use of correction fluid is not permitted.
Corrections made after the Investigator’s review and signature of the completed CRF will be 
resigned and dated by the Investigator.
The Investigator should maintain a list of personnel authorized to enter data into the CRF. 
Detailed instructions will be provided in the CRF completion guidelines.
12.3.2
Database entry and reconciliation
Case report forms/external electronic data will be entered/loaded in 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.
An electronic audit trail system will be maintained within the CDMS to track all data changes 
in the database once the data has been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
REDACTED 
e s
mplet
mplet
omp
omp
COPY
cord
cor
data re
ata 
spec
spec
This document 
heck
ec
cons
cons
inin
cannot
port 
port 
base u
ase u
cks
ks
be
f
used
ctions
tions
Da
Da
to
ould
ould
support
Inve
Inve
he I
e Inve
nv
ld m
d m
any
inal e
nal 
st
marketing
pt repo
pt repo
RF sho
RF sh
en
authorization 
epo
p
cified 
ified 
tion
on
application
ata obt
ta ob
ng acc
ng ac
ngs fro
gs fr
ported
orte
and any 
m
extensions 
nts.
nts.
nd the
d the
m rec
re
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 49 of 119
12.3.3
Subject Entry and Enrollment log/Subject Identification Code list
The subject’s entry and enrollment will be recorded in the Subject Entry 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.
12.4
Termination of the study
Upon completion of the study, the monitor will conduct the following activities in 
conjunction with the Investigator, as appropriate:
•
Return of all study data to UCB or its representatives while maintaining original source 
documents
•
Data clarification and/or resolution
•
Accountability, reconciliation, and arrangements for used and unused investigational 
products
•
Review of site study records for completeness
•
Discussion/reminder on archiving responsibilities
•
Discussion of IRB/IEC requirements for study termination
•
Arrangements for unused CRFs, lab supplies, and any other study related supplies
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at 
a single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform 
the Investigators/institutions, and the regulatory authority(ies) of the termination or 
suspension and the reason(s) for the termination or suspension, in accordance with applicable 
regulatory requirement(s). The IRB/IEC should also be informed and provided with reason(s) 
for the termination or suspension by the Sponsor or by the Investigator/institution, as 
specified by the applicable regulatory requirement(s). In addition, arrangements will be made 
for the return of all unused investigational products and other material in accordance with 
UCB procedures for the study.
12.5
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.
REDACTED
biliti
bilit
or stud
r stud
ab supp
b sup
COPY 
ies
i
This document
12.5
12.5
T
cannot
by
return
return
B proc
B proc
be 
na
y the
y the
sed
e r
ireme
reme
ation
ation
to
reas
reas
support 
th h
ely term
y ter
utions
ution
any
ate or
ate o
resp
res
marketing 
p
y suspe
susp
l sites 
l sites
or i
authorization 
s
dy
dy term
term
y
lies, 
ies,
application 
nd unus
d unu
and any
orig
orig
extensions 
gini
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 50 of 119
All essential documents are to be retained by the Investigator until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by the applicable 
regulatory requirement(s) or by an agreement with UCB (ICH-GCP Guideline, 
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.
12.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB and inspections by 
domestic or foreign regulatory authorities, after reasonable notice.
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).
12.7
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.
13
STATISTICS
A description of statistical methods is presented below and will be described in more detail in 
the Statistical Analysis Plan (SAP).
13.1
Definition of analysis sets
The All Subject Population will include those subjects who are enrolled in the study. All 
available data entered into the database will be listed for this population.
The Safety Population will include all subjects enrolled who receive at least 1 injection of 
study treatment in this study. This population will be used to summarize the safety, PK, and 
immunological variables.
The Intention-to-Treat (ITT) Population will include all subjects irrespective of any protocol 
deviations who receive at least 1 injection of study treatment in this study and who have at 
least 1 efficacy measurement after the first injection of this study. This population will be 
used to summarize the efficacy variables.
REDACTED
all stu
all st
rity
ity is 
is 
y
actic
actic
COPY
RB/IE
RB/I
d
This document 
he e
stud
stud
im
im
cannot
Subj
Subj
able da
ble da
Sa
Sa
be 
bje
bje
used
nalylys
De
De
to 
tisti
tisti
sis
sis
support 
he
he
STICS
TIC
tical 
ica
any
ance
anc
e stud
stud
marketing 
e
H/GCP
H/GC
staff, 
staff
ce C
ce
authorization 
dy
dy do
do
y
annou
annou
application 
sig
sig
that all 
hat al
mplian
mplia
C SOP
SO
and
hts an
ts an
gnin
gnin
any 
nd
extensions 
ctions
tions
or 
a
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 51 of 119
13.2
General statistical considerations
Summary statistics will consist of sample size, frequencies, and corresponding percentages 
for categorical variables. For continuous variables, descriptive statistics (number of available 
observations, mean, median, standard deviation, minimum, and maximum) will be tabulated. 
Data summarized by visit will use nominal visits with the exception of data collected at 
withdrawal visits which will be summarized at the next scheduled nominal visit dependent on 
when the withdrawal visit occurs taking into account the allowable visit windows.
Summaries will be by treatment received at the end of C87035. Any other subgroups of 
interest such as subjects who have been reinduced in C87035 or reinduced during CR0012 
will be detailed in the SAP.
For data such as Crohn’s disease history which are only collected at the Screening Visit of 
C87035, these will be defined as the Baseline values. For data which are collected at Week 0 
of C87035 and prior to receiving any study treatment, the last nonmissing value prior to 
receiving any treatment will be defined as the Baseline values.
All analyses will be performed using the SAS software package.
All AEs will be coded and classified by primary System Organ Class (SOC) and Preferred 
Term (PT) according to the most recent version of the Medical Dictionary for Regulatory 
Activities (MedDRA®).
All medications will be coded using World Health Organization Drug (WHODrg).
13.3
Planned safety analyses
All safety summaries will be based on the Safety Population as a whole, by treatment group, 
weight, and age stratum.
Treatment emergent adverse events will be summarized descriptively by primary SOC, high 
level term, and PT. Additional tables will summarize AEs by severity and relationship to 
study drug, and separate tables will be generated for AEs leading to withdrawal from the 
study, SAEs, and deaths. Other AEs of special interest including, but not limited to, 
infections will also be summarized.
The specific set of AEs reported as injection reactions will also be summarized along with 
their classification as either injection site reactions or systemic hypersensitivity reactions (the 
latter being further classified as acute or delayed).
Actual laboratory values and changes from Baseline in laboratory values will be summarized. 
Shift tables to show the change from Baseline in the absolute values and details of treatment 
emergent markedly abnormal values (based on Common Terminology Criteria for Adverse 
Events criteria) will be presented by variable.
Actual vital signs values and change from Baseline in vital signs values will be summarized. 
Autoantibody levels will be assessed via the presence or absence of ANA and anti-dsDNA, 
and data will be summarized. 
Extent of exposure to treatment will be presented descriptively.
REDACTED
alth 
alth 
ses
ses
the S
the S
COPY
 Me
 Me
O
This document 
ven
e
Act
Act
cannot
bles t
es t
gent m
gent m
nts c
nts c
be
orato
orato
tot
used 
n as
a
ther c
her c
to
E
as ei
as e
support
her 
her 
mmari
mmar
s repo
s rep
any
will b
will 
r AE
r A
marketing 
af
will be 
will be
les wil
es w
b
authorization 
Organi
rgani
fet
fety
application 
n Class
n Clas
ical Di
cal D
and 
g
any 
ect
ec
value 
value
extensions 
0012 
012 
ing Vi
ng Vi
cted
ted
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 52 of 119
13.4
Planned efficacy analyses
As the primary objective of the study is to evaluate safety there are no primary or secondary 
efficacy variables. Rather, efficacy variables will be measured to evaluate efficacy of 
longterm open label treatment with CZP.
All efficacy summaries, where applicable, will be presented by visit, treatment group, weight 
(20 to <40kg [44 to <88lbs] and ≥40kg [≥88lbs]) and age stratum (6 to 11 years and 12 to 
17 years). 
The proportion of subjects in clinical remission and the proportion of subjects in clinical 
response will be summarized using the number and percentage of subjects along with 
associated 95% confidence intervals (CI). 
A subject who does not have all required data to derive a response status (response or 
remission) will be classified as a nonresponder/nonremitter at that particular time point. A 
subject who withdraws from the study or is reinduced, will be classified as a 
nonresponder/nonremitter from and including the time of withdrawal or reinduction.
If a subject receives rescue therapy, the subject will be considered as a treatment failure 
(nonresponder/nonremitter) from the timepoint of administration of first rescue therapy 
onwards.
Actual PCDAI scores and changes from Baseline in PCDAI scores will be summarized by 
presenting the mean, standard deviation (SD), 95% CI for the mean, median, minimum, and 
maximum values.
Levels of CRP and ESR and changes from Baseline in CRP levels and ESR (expressed as a 
ratio with the value measured at Baseline as denominator) will be summarized by presenting 
the geometric mean, coefficient of variation, 95% CI for the geometric mean, median, 
minimum, and maximum values.
IMPACT-III scores and changes from Baseline will be summarized by presenting the mean, 
SD, 95% CI for the mean, median, minimum, and maximum values.
The change from Baseline in growth score using the Tanner stage (assessing puberty), will be 
summarized using shift tables. Bone marker values and changes from Baseline in bone 
marker values will be summarized.
The proportion of days missed from school/work will be summarized by presenting the mean, 
SD, 95% CI for the mean, median, minimum, and maximum values.
Actual WPAI:CD scores and changes from Baseline in WPAI:CD scores will be summarized 
by presenting the mean, SD, 95% CI for the mean, median, minimum, and maximum values.
The summaries will be presented separately for the WPAI:CD for children, WPAI:CD for 
working individuals with CD, and WPAI:CD for caregivers. Direct costs parameters will be 
summarized by period of onset using descriptive statistics.
REDACTED
95%
95%
om Ba
om B
eline a
eline a
ria
ria
COPY 
in PC
in PC
C
This document
he e
work
work
su
su
cannot
WPA
WPA
esenti
esenti
 sum
sum
be 
fo
AI
AI
used 
of da
of da
or th
r th
to
be su
be s
support 
e in gr
in g
ft table
t table
sum
sum
any
fro
fr
dian, m
ian, m
marketing
as de
s de
ation, 9
tion, 9
om B
om
authorization
CDAI
CDAI
CI 
CI for 
for 
aselin
selin
den
en
application 
d as a t
s a 
on of f
on of 
I s
and 
as 
as
or rei
or rei
any
r tim
r tim
a
extensions 
onse o
nse o
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 53 of 119
13.5
Pharmacokinetics and immunological analyses
Plasma concentrations of CZP at each visit will be summarized and plotted by anti-CZP 
antibody status (all subjects, antibody-positive, and antibody negative) for each age stratum, 
the overall population, and for the treatment groups. In addition, plasma concentrations will 
be summarized and plotted by weight stratum (<40kg; ≥40kg) for the treatment groups.
Individual anti-CZP antibody concentrations will be listed and the incidence of anti-CZP 
antibody positive subjects will be summarized by study visit and overall incidence by age 
stratum and by treatment group. Anti-CZP antibody positive status is defined as a subject 
having a value >2.4units/mL anti-CZP antibody at any time during the study.
Additionally, the PK data collected in CR0012 may be used for population PK modeling to 
supplement or validate the pediatric model derived from the data obtained in C87035. If 
performed, the analysis and results of this modeling will be provided in a separate report.
13.6
Handling of protocol deviations
No Per Protocol population is defined in this study and thus no consideration with regards to 
deviations affecting such a population need to be considered. Nevertheless, for each interim 
analysis and final analysis, after all the data have been verified/coded/entered into the 
database, a review will be performed after last subject last visit. The purpose of this review 
will be to primarily check the quality of the data. The review will also help decide how to 
deal with problems in the subject’s data (for example: missing values, withdrawals, drop outs, 
protocol deviations). In addition, the review will be used to identify the use of rescue therapy. 
The preanalysis reviewers should ensure that the results of this review are communicated to 
the study team before locking the database.
After the preanalysis review, resolution of all issues and documentation of all decisions, the 
database will be locked.
13.7
Handling of dropouts or missing data
For responder type variables, should a subject withdraw prior to completion of the study, then 
the subject will be classified as a nonresponder or nonremitter from and including the time of 
withdrawal.
A subject who does not have all the required data to derive a response status will be classified 
as a nonresponder or nonremitter at that particular time point.
If a subject receives rescue therapy or discontinues study treatment, then the subject will be 
classified as a treatment failure (nonresponder or nonremitter) from and including the time of 
the event, regardless of their score (PCDAI).
If a subject loses response and is reinduced, the subject will be classified as a nonresponder 
or nonremitter from and including the time of the reinduction.
In addition, for any other efficacy variables, no data will be used from and including the time 
of receiving rescue therapy in the summaries and analyses where relevant.
Unless part of an accepted imputation technique, any missing data during the study will 
remain missing.
REDACTED 
amp
amp
will be
will b
hat the
at th
base.
base.
on o
on o
COPY
t last
t las
The rev
The re
mple:
ple
This document 
f a s
a 
or no
or no
I
cannot 
d as
as
ent, re
ent, r
subj
sub
be
rece
ece
s a
s a
used
der or
r or
ceiv
eiv
to
not
not
support
 s
ed as a
ed as 
t h
any 
hould
hould
marketing 
of all i
of all i
opou
pou
authorization
view
iew
: miss
miss
e used
e used
e resu
e resu
application 
ide
de
verthel
erthe
d/coded
d/code
visit. T
isit. T
ew w
w w
and 
erat
erat
any 
ara
ar
extensions 
deling
deling
87035
7035
rate
ate
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 54 of 119
If an AE has severity and/or relationship missing then the event will be assumed to be severe 
and/or highly probably related to the treatment.
For the WPAI:CD, handling of dropouts or missing data will be detailed in the SAP.
13.8
Planned interim analysis and data monitoring
A DSMB will review safety data. The DSMB members will be independent of the Sponsor 
and Investigators. The DSMB members will be informed by GCSP (or designee) of all SAEs 
at the time of expedited reporting and will review periodically all emerging safety data 
(SAEs, AEs, safety laboratory data). Based on the safety data, the DSMB can recommend 
modifying/stopping the study.
No interim analyses are planned. Should a regulatory authority request an interim analysis, 
this will be performed according to the request.
13.9
Determination of sample size
This is an open-label study for subjects who completed C87035 and as such no formal sample 
size has been determined.
14
ETHICS AND REGULATORY REQUIREMENTS
14.1
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 and his/her parent(s)/legally acceptable 
representative(s) in both oral and written form by the Investigator (or designee). Each subject 
and his/her parent(s)/legally acceptable representative(s) will have the opportunity to discuss 
the study and its alternatives with the Investigator.
Prior to participation in the study, the written Informed Consent form should be signed and 
personally dated by the subject, or his/her legal representative, and by the person who 
conducted the informed consent discussion (Investigator [or designee]). If applicable, a child 
Assent form may be used. The subject or his/her legal representative must receive a copy of 
the signed and dated Informed Consent/child Assent form. As part of the consent process, 
each subject must consent to direct access to his/her medical records for study-related 
monitoring, auditing, IRB/IEC review, and regulatory inspection.
If the Informed Consent/child Assent form is amended during the study, the Investigator (or 
the Sponsor, if applicable) must follow all applicable regulatory requirements pertaining to 
the approval of the amended Informed Consent form by the IRB/IEC and use of the amended 
form.
All studies conducted at centers in the United States must include the use of a Health 
Insurance Portability and Accountability Act (ie, HIPAA) Authorization form.
The subject and his/her parent(s)/legally acceptable representative(s) may withdraw their 
consent to participate in the study at any time. A subject is considered as enrolled in the study 
REDACTED 
d d
d d
ethica
ethica
nform
nform
subj
subj
COPY 
docu
doc
This document
the a
he a
for
for
cannot 
g
Inform
nform
Spon
Spon
be
, aud
, aud
used 
dated 
ated 
must c
must c
to
e use
e us
I
support
stud
tud
ubject,
ubjec
d cons
d cons
ed
any
h th
h th
dy
dy
marketing
mat
ect an
ct an
ten for
en fo
table re
able r
he I
he
authorization 
umen
umen
al prin
l prin
tion 
ion 
application 
UIREM
UIRE
and 
s such
such
any extensions 
nd 
m anal
m anal
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 55 of 119
when his/her parent(s)/legally acceptable representative(s) has signed the Informed Consent 
form. 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.
14.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject or legal 
representative will be provided with a subject identification card in the language of the 
subject. The Investigator will fill in the name of the study and medical emergency contact 
information. The Investigator will instruct the subject to keep the card with them at all times.
14.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local 
regulations, ICH-GCP, and in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki.
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies 
with the requirements of the current ICH-GCP version or applicable country-specific 
regulations will be responsible for the initial and continuing review and approval of the 
clinical study. Prior to initiation of the study, the Investigator/UCB will forward copies of the 
protocol, Informed Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if 
applicable), advertisement (if applicable), and all other subject-related documents to be used 
for the study to the IRB/IEC for its review and approval.
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol.
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to human subjects or others, and any protocol 
deviations, to eliminate immediate hazards to subjects.
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the subjects. 
For minor changes to a previously approved protocol during the period covered by the 
original approval, it may be possible for the Investigator to obtain an expedited review by the 
IRB/IEC as allowed.
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 the Committee’s 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.
REDACTED 
ll ot
ll o
nd app
nd app
r will 
r will 
COPY
estiga
stig
rochur
rochu
othe
oth
This document 
RB/
B/
UC
UC
cannot
on th
on th
lved b
ved b
B/IE
/IE
be
r wil
r wi
used 
ed.
ed
IRB/
IRB/
to 
ma
ma
d
support
ke
ecessar
cessa
previo
previ
may
ay b
y
any 
an
any
marketing 
port to t
ort to
sks to h
ks to
haza
haz
authorization
ure, I
e, 
er sub
r sub
proval
roval
have w
have w
application 
IRB
RB
able cou
ble co
eview a
view
tor/UCB
or/UC
Inv
Inv
and 
B/IE
B/I
any
ve th
ve th
extensions 
ocal
cal
h
or 
es.
es.
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 56 of 119
14.4
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 in C87035.
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).
14.5
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.
15
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements as applicable.
16
REFERENCES
Griffiths AM, Nicholas D, Smith C, Munk M, Stephens D, Durno C, et al. Development of a 
quality-of-life index for pediatric inflammatory bowel disease: dealing with differences 
related to age and IBD type. J Pediatr Gastroenterol Nutr. 1999;28(4):S46-S52.
Hanauer SH, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. 
Maintenance infliximab for Crohn’s Disease: the ACCENT I randomised trial. Lancet. 
2002;359(9317):1541-49.
Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, et al. 
Development and validation of a pediatric Crohn’s disease activity index. J Pediatr 
Gastroenterol Nutr. 1991;12(4):439-47.
Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J, et al. Induction and 
maintenance infliximab therapy for the treatment of moderate to severe Crohn’s disease in
children. Gastroenterology. 2007;132(3):863-73.
Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 
1969;44(235):291-303.
Marshall WA, Tanner JM. Variations in pattern of pubertal changes in boys. Arch Dis Child. 
1970;45(239):13-23.
REDACTED 
g to lo
g to lo
ts are a
s are 
COPY 
AND 
AND
This document 
main
ain
child
child
cannot
ntero
tero
ms J, C
ms J, C
nten
nten
be
nt an
t a
rol N
rol
used 
rry GD
GD
y
and
and
to
41
41-4
support 
J P
J 
G, Licht
ich
ab for 
b for
49
49
any
c inf
c in
Pedia
Pedia
marketing 
C, Mun
, Mu
nfla
nfl
authorization
PU
PU
ocal re
cal re
addres
ddres
application 
ndment
dmen
uthoriti
uthori
B
and 
llilin
any 
y als
al
y
ng it
ng
extensions
eport
port
or 
ries
ries
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 57 of 119
Otley A, Loonen H, Parekh N, Sherman PM, Griffiths AM. Assessing activity of pediatric 
Crohn’s disease: which index to use? Gastroenterology. 1999;116(3):527-31.
Otley A, Smith C, Nicholas D, Munk M, Avolio J, Sherman PM, et al. The IMPACT 
questionnaire: a valid measure of health-related quality of life in pediatric inflammatory 
bowel disease. J Pediatr Gastroenterol Nutr. 2002;35(4):557-63.
Reilly MC, Gerlier L, Brabant Y, Brown, M. Validity, reliability and responsiveness of the 
Work Productivity and Activity Impairment questionnaire in Crohn’s disease. Clin Ther. 
2008; 30(2):393-404.
Rutgeerts P, D'Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, et al. Efficacy 
and safety of retreatment with anti-tumour necrosis factor antibody (infliximab) to maintain 
remission in Crohn’s Disease. Gastroenterology. 1999;117(4):761-9.
Sandborn WJ, Feagan BG, Hanauer SB, Present DH, Sutherland LR, Kamm MA, et al. An 
engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized 
double-blind placebo-controlled trial. Gastroenterology. 2001;120(6):1330-8.
Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, et al. A short 
term study of chimeric monoclonal antibody cA2 to tumour necrosis factor alpha for Crohn’s 
Disease. Crohn’s Disease cA2 Study Group. N Engl J Med. 1997;37(15):1029-35.
REDACTED COPY
Med
Me
This document cannot be used to support any marketing authorization application 
Braak
Braak
ecrosis 
ecrosis
1997;
1997
and 
e: a
: 
1330
330
any
m MA
m MA
a ran
a ra
extensions
fficacy
fficacy
maint
maint
A
or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 59 of 119
17.2
Pediatric Crohn’s Disease Activity Index
Instructions on scoring are provided in the PCDAI’s user guide following the questionnaire. 
Scoring items are marked with an asterisk (*).
HISTORY (Recall; 1 week)*
Abdominal pain*:
None
(0)
Mild – Brief, does not interfere with activities
(5)
Mod / severe - daily, longer lasting, affects activities, nocturnal
(10)
Stools (per day)*:
Formed stools or up to 1 liquid stool, no blood
(0)
Up to 2 semi-formed with small blood, or 2 to 5 liquid with or without 
small blood
(5)
Any gross bleeding, or ≥ 6 liquid, or nocturnal diarrhea
(10)
Patient Functioning – General Well-Being*:
No limitation of activities, well
(0)
Occasional difficulty in maintaining appropriate activities, below par
(5)
Frequent limitation of activity, very poor
(10)
REDACTED 
od
or 2 to
or 2 t
COPY 
This document cannot
ent lim
nt li
be 
d
used 
c
ifficu
fficu
to
ctivi
tivi
support 
ner
e
tie
any 
ral W
ral
marketing 
noctur
noctu
authorization 
o 5 liq
o 5 liq
application and any 
any extensions 
(0
(
te
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 60 of 119
LABORATORY
Hematocrit (%)
≤10 yrs:
≥33
(0)
28-32
(2.5)
<28
(5)
Males 11-14yrs:
≥35
(0)
30-34
(2.5)
<30
(5)
Males 15-19yrs:
≥37
(0)
32-36
(2.5)
<32
(5)
Females 11-19yrs :
≥34
(0)
29-33
(2.5)
<29
(5)
ESR (mm/h)
<20
(0)
20-50
(2.5)
>50
(5)
ALBUMIN (g/dL)
≥3.5
(0)
3.1-3.4
(5)
≤3.0
(10)
REDACTED COPY 
This document cannot be
N (g
N (g
used 
(g/d
g/d
to support any marketing authorization application 
<32
<32
and any 
a
extensions 
(0)
0)
(2.
(2.
io
xt
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 61 of 119
EXAMINATION
Weight*:
Weight gain or voluntary weight stable/loss
(0)
Involuntary weight stable, weight loss 1-9%
(5)
Weight loss ≥10%
(10)
Height* - Score using (a) criteria when possible
a)
Height velocity  ≥-1SD
(0)
Height velocity < -1SD, >-2SD
(5)
Height velocity  ≤ -2SD
(10)
OR
b)
< 1 channel decrease
(0)
≥1 to < 2 channel decrease
(5)
≥ 2 channel decrease
(10)
Abdomen
No tenderness, no mass
(0)
Tenderness, or mass without tenderness
(5)
Tenderness, involuntary guarding, definite mass
(10)
REDACTED COPY 
This document
Ten
Ten
cannot 
dernes
ernes
d
be
ness
ness
used to support any marketing authorization application and any extensions 
5)
(10
(10
n
te
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 62 of 119
Perirectal disease
None, asymptomatic tags
(0)
Inflamed tags or 1-2 indolent fistula(e) or fissure(s), scant drainage, no 
tenderness
(5)
Active fistula, drainage, tenderness, or abscess
(10)
Extra-intestinal Manifestations
Fever ≥ 38.5ºC for 3 days over past week, oral ulcers, definite arthritis, uveitis, erythema 
nodosum, P. gangrenosum
None
(0)
One
(5)
≥ Two
(10)
TOTAL SCORE
REDACTED COPY 
This document cannot be used to support any marketing authorization application
hritis
itis
and 
is
any extensions 
0)
0)
on or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 63 of 119
PCDAI USER’S GUIDE
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with CD participating in clinical trials.
HISTORY
All calculations are based upon a 1-week (7-day) history recall of symptoms. The history 
recall should be solicited from the patient and/or caregiver.
1. Abdominal pain
The descriptions in the PCDAI of “mild” and “moderate/severe” should be used to guide in 
scoring the pain. Note that duration, effect on activities, and nocturnal occurrence separate 
moderate/severe from mild. If pain varies in severity during the week, patient should be 
scored according to the most severe pain. However, mild pain should be present on at least 
two days to score 5 points rather than 0 points.
2. Stools
The intent is to score the stool pattern during the preceding week.
To facilitate scoring, first categorize the patient as having blood in the stool or not.
If there is no blood in the stool, score as follows:
•
Formed stools or up to 1 loose stool daily = 0 
•
Two to five liquid or very loose stools on 1 or more days = 5
•
Six or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10
If blood is present in the stool on any day during the past week, score as follows:
•
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
•
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
3. Patient functioning, general well-being
If there is variation during the week, patient should be scored according to the most 
significant limitation of activity, even if only one day of the week, as long as likely due to 
Crohn’s disease and not to an intercurrent illness.
REDACTED 
s:s:
ilyly = 0
= 0
y
ools on
ools o
too
to
COPY 
dini
having
avin
This document cannot be
m
sease
seas
used
ion d
on d
mitatio
itati
to 
ning
in
support
rge am
ge a
ng, g
g,
any
tool 
tool
m
marketing 
n
ols on 
ls on 
ny day
 day
y
(o
(
authorization 
g b
0
1 or
1 or
application 
week.
eek.
blood
loo
and 
 pre
pre
any
nt sh
nt sh
resen
ese
extensions 
to gui
to gui
nce se
nce s
h
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 64 of 119
PHYSICAL EXAMINATION
4. Weight
The intent is to assess the ability to normally maintain or gain weight.
Voluntary weight stable/loss means patient maintaining or losing weight on purpose.
Involuntary weight stable means patient wants to gain weight but cannot.
To calculate percentage weight loss use formula:
Historic weight – Current weight
X 100 = % weight loss
Historic weight
Take historic weight as maximal weight attained within preceding 4 to 6 months, excluding 
any value that reflects excess weight due to corticosteroid use.
5. Height
The intent is to assess the normalcy vs impairment of the patient’s recent linear growth. 
Note that post-pubertal patients will score 0 points. For patients still growing, there are 
2 options for scoring. Method (a) is preferred. Method (b) to be used if data required for (a) 
are unavailable.
Method (a):
Height velocity (cm/year), the most sensitive parameter, should be used if reliable height 
measurements are available from the preceding 6 to 12 months.
Convert height increment during preceding 6 to 12 months into velocity (cm/year) as follows:
Present height – Height 6 – 12 months previously
X 12  = Height velocity (cm/year)
Interval (months) between heights
Using height velocity chart, determine centile for height velocity (see below for a copy).
Height velocity should ideally be plotted according to bone age rather than chronologic age. 
However, if maturity is appropriate for age (not delayed or advanced) it is reasonable to plot 
and score height velocity according to chronologic age. 
REDACTED
ints.
ints
d. Met
d. Met
COPY 
of the 
of the 
F
This document 
d 
canno
veloc
eloc
ever, i
ver, i
scor
scor
be 
t ve
cit
cit
used 
veloc
eloc
to 
mo
support
6 – 1
onths)
nths
pp
any
g pre
g pr
2
marketing 
nsitive 
nsitiv
e prece
prec
ece
ec
authorization 
p
For pat
or pa
thod (
hod (
application 
to
patien
atien
and 
o 6 m
6 m
any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 65 of 119
In follow-up visits of short-term clinical trials less than 4 months duration, score height 
velocity the same as the initial score unless there has been an actual height gain.
Method (b):
If reliable height measurements from 6 to 12 months previously are lacking (often the case 
with newly diagnosed patients), use any earlier heights to assess previous height centile and 
compare with current height centile. Score according to degree of decrease in height centile. 
Guidelines to calculate and incorporate the results of the Height velocity (cm/year) into 
the PCDAI
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations 
o
thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 66 of 119
Height Velocity Reference Values for Calculating the PCDAI (Males)
Age (years)
Height Velocity in cm per year (Males)
Minus 2SD
Minus 1SD
Mean
2.5
5.7
7
8.3
3
5.4
6.6
7.8
3.5
5.1
6.3
7.4
4
4.9
6
7.1
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.4
6.4
6
4.3
5.3
6.2
6.5
4.2
5.1
6
7
4.2
5
5.9
7.5
4.1
4.9
5.8
8
3.9
4.8
5.6
8.5
3.8
4.6
5.4
9
3.8
4.5
5.3
9.5
3.7
4.5
5.2
10
3.7
4.4
5.1
10.5
3.7
4.4
5.1
11
3.7
4.4
5.2
11.5
3.8
4.6
5.3
12
4
4.9
5.7
12.5
4.8
5.8
6.7
13
6.2
7.4
8.6
13.5
7.1
8.3
9.5
14
6.1
7.2
8.4
14.5
4.1
5.3
6.5
15
2.4
3.6
4.7
15.5
1.2
2.3
3.3
16
0.4
1.3
2.2
16.5
0.1
0.7
1.5
17
0.1
0.4
0.9
17.5
0.1
0.1
0.5
REDACTED 
D
CT
AC
DA
RE
COPY 
4.6
Y
O
This document 
6.5.5
17
17
en
um
um
um
u
cannot 
no
ca
be 
be used 
d
se
us
to support 
6.2
6.
rt
pp
s
any 
8
ny 
a
marketing 
g
ng
ket
ma
authorization 
4.5
4.5
n
ati
ori
ut
application 
n
at
pl
a
and 
nd any 
.2
6
any extensions 
en
en
en
en
ex
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 67 of 119
Height Velocity Chart (males)
ACTED 
REDAC
R
COPY 
C
This documen
ment 
me
nnot 
cann
be used 
u
to
to 
ort 
suppor any 
ting 
marketin
m
ion 
thorizatio
autho
lication 
applic
and 
a
ny 
any
s 
nsions
extens
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 68 of 119
Height Velocity Reference Values for Calculating the PCDAI
(Females)
Age (years)
Height Velocity in cm per year (Females)
Minus 2SD
Minus 1SD
Mean
2.5
5.9
7.3
8.6
3
5.5
6.9
8.1
3.5
5.2
6.4
7.6
4
4.9
6.1
7.2
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.5
6.4
6
4.4
5.3
6.2
6.5
4.3
5.2
6.1
7
4.3
5.2
6
7.5
4.3
5.1
5.9
8
4.2
5
5.8
8.5
4.2
4.9
5.7
9
4.2
5
5.8
9.5
4.3
5
5.8
10
4.4
5.3
6.2
10.5
4.7
5.7
6.8
11
5.7
6.6
7.7
11.5
6.1
7.2
8.3
12
5.2
6.3
7.3
12.5
3.6
4.8
5.9
13
2.4
3.3
4.3
13.5
1.3
2.2
2.9
14
0.4
1.1
1.8
14.5
0
0.5
1
REDACTED 
5
4.9
4 9
ED
CT
ED
R
COPY 
PY 
CO
This document cannot 
ot
no
c
be 
be used 
d
us
to
3
t
suppo
.2
port 
po
6
su
any y
a
marketing 
ting
rk
m
authorization 
n 
za
5
ho
au
application 
6.1
6.1
n
ca
pp
ap
and 
nd
nd
nd
nd any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 69 of 119
Height Velocity Chart (females)
CTED 
REDACT
R
COPY 
CO
This document
ent 
en
not 
cann
be used 
us
o
to 
rt 
support
s
any 
ng 
marketing
ma
on 
horization
autho
ication 
applica
and 
an
y
any 
sisions 
extensi
or r
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 70 of 119
Calculating height velocity:
1.
Use the present height and height measurement during proceeding 6-12 months.
2.
Calculate the height velocity as follows;
Present height – Height (6 – 12 months previously) x 12 = Height velocity (cm/year)
Interval (months) between heights
Ideally, bone age rather than chronologic age should be used. However, if maturity is 
appropriate for age (not delayed or advanced) it is reasonable to use chronologic age. 
Scoring for the PCDAI:
Velocity less than “Minus 2 SD” scores 10 points
Velocity between “Minus 2 SD” and “Minus 1 SD” scores 5 points
Velocity greater than “Minus 1 SD” scores zero points.
Example:
If the subject is a male who is 10 years old: 
1. Use the present height and height measurement during proceeding 6-12 months.
2. Calculate the height velocity as per equation provided.
3. For example in this 10-years-old male the height velocity comes up to 4 cm/year.
4. Next step refer to the table for height velocity values reference for males (provided).
5. You will notice that the 4 cm height velocity falls between the range of minus2SD 
and minus1SD. 
6. The score for the PCDAI will be (5 points) as per above scoring guideline.
7. Go to the PCDAI and enter  the #5 and complete the scoring of the PCDAI.
References:
REDACTED 
rs o
rs o
COPY 
SD
S
zero 
zero
This document cannot
The 
The 
7.7. G
be
min
min
used 
refe
ill not
ll no
nu
to
fer t
fer 
support
ht velo
velo
n this 10
this 1
any
nd he
nd h
oc
marketing 
old:
ld:
i
authorization 
po
p
application 
scores 
cores
oints
oints
and any extensions 
ty is
y is 
ic age
c age
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 71 of 119
1. J.M. Tanner, Davies PSW. Clinical Longitudinal Standards for height and height velocity 
for North American children. J Pediatr 1985;107:317-29.
2. Jeffery Hyams, George D. Ferry, etal, development and validation of a pediatric Crohn’s 
disease activity index. J of Pediatric Gastroenterology and Nutrition 1991:12:439-47.
REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

REDACTED COPY 
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 86 of 119
17.7
Protocol amendment #1
Rationale for the amendment
The telephone numbers for reporting SAEs during business hours or outside business hours 
have been indicated. The inclusion and exclusion criteria were simplified to include any 
subject who completed C87035. Pregnancy due to oral contraceptive failure is not considered 
an SAE; the change was made to comply with Sponsor SAE reporting procedures. An 
additional example of an important medical event relevant to subjects with CD (infections 
that require treatment with parenteral antibiotics) was provided. An inconsistency in Visit 2 
vital signs compared to the Schedule of Study Assessments was corrected in Section 9.6.7.
Specific changes
Change # 1 –Serious adverse reporting telephone numbers (page 5)
Serious adverse event reporting (24h), safety related issues, and emergency unblinding
Fax
Europe and Rest of the World (except Japan): +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Phone
Europe and Rest of the World (except Japan): +32 2 386 24 68
USA & Canada: +1 678 799 4007
Has been changed to:
Serious adverse event reporting (24h), safety related issues, and emergency unblinding
Fax
Europe and Rest of the World (except Japan): +32 2 386 24 21
USA: +1 800 880 6949
Canada: +1 877 582 8842
Phone
During business hours:
Outside business hours:
Europe and Rest of the World 
(except Japan): +32 2 386 24 68
USA & Canada:
+1 770 970 2709
Europe and Rest of the World 
(except Japan): +32 2 386 24 68
USA & Canada:
+1 678 799 4007
Change #2 - Inclusion criterion (Section 6.1) 
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved 
written Informed Consent form is signed and dated by the subject or by the parent(s) or 
legally acceptable representative. The Consent form or a specific Assent form, where 
required, will be signed and dated by minors.
REDACTED 
AC
)
RE
COPY 
pt Jap
pt Jap
PY
This document
Chan
Chan
To
T
cannot 
ca
be 
U
be used 
urop
rop
(excep
excep
US
US
to 
pe
pe
o support 
8
 877 5
877
busin
busin
pp
s
any
of th
f t
0 694
0 694
ma
the W
the
marketing 
, safety
safety
g 
ma
authorization
pan):
an)
ho
application
386 2
86 2
+
ap
and 
a
any 
y y unb
unb
y extensions 
.6.7.
6.7.
or 
2
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 87 of 119
2. Subject/parent(s)/legally acceptable representative is considered reliable and capable of 
adhering to the protocol, visit schedule or medication intake according to the judgment of 
the Investigator.
3. Subject satisfied the Inclusion criteria at time of entry into C87035 and completed the 
study (Week 62 Visit). 
4. Subject’s current or recent regimen of concomitant medication(s) for CD should be stable 
through the study period (see Section 7.8.1).
Has been changed to:
To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved 
written Informed Consent form is signed and dated by the subject or by the parent(s) or 
legally acceptable representative. The Consent form or a specific Assent form, where 
required, will be signed and dated by minors.
2. Subject/parent(s)/legally acceptable representative is considered reliable and capable of 
adhering to the protocol, visit schedule or medication intake according to the judgment of 
the Investigator.
3. Subject completed the C87035 study (Week 62 Visit). 
4. Subject’s current or recent regimen of concomitant medication(s) for CD should be stable 
through the study period (see Section 7.8.1).
Change #3 - Exclusion criterion (Section 6.2) 
Subjects are not permitted to enroll in the study if the following criterion is met:
1. Any exclusion criterion that would have prevented the subject from participation in 
C87035.
Has been changed to:
Subjects are not permitted to enroll in the study if the following criterion is met:
1. Subject did not complete the C87035 study (Week 62 Visit).
Change #4 – Pregnancy (Section 9.1.6; last paragraph)
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion, or anomaly/birth defect of the child. Pregnancy is considered as an 
SAE in case of contraceptive failure (eg, birth control pill taken each day without having 
been forgotten or use of permanent contraceptive devices). Those SAEs must be additionally 
reported using the Investigator SAE Report form.
Has been changed to:
A pregnancy becomes a serious adverse event (SAE) in the following circumstances: 
miscarriage, abortion, or anomaly/birth defect of the child. Pregnancy is considered as an 
SAE in case of contraceptive failure (eg, birth control pill taken each day without 
REDACTED
omit
omi
8.1).
.1).
on 6.2
on 6.2
n the 
n the 
COPY 
62 Vis
2 V
itan
itan
This document
been 
been
rep
rep
cannot
ancy
ncy
rriage
riage
E in c
E in c
f
be 
P
y b
y
used 
Preg
Preg
to support
to enr
to en
omplet
mple
any marketing
study
stud
d have 
d have
authorization 
sit)
nt med
nt me
2) )
application
d rel
rel
accord
accor
t). 
). 
and 
liaia
any
nt form
nt for
extensions 
approv
pprov
e par
par
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 88 of 119
having been forgotten or use of permanent contraceptive devices). Those SAEs must be 
additionally reported using the Investigator SAE Report form.
Change #5 – Definition of serious adverse event (Section 9.2.1; bullet 3)
•
Important medical event that, based upon appropriate medical judgment, may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one 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.)
Has been changed to:
•
Important medical event that, based upon appropriate medical judgment, may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one 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, infections that require treatment with parenteral antibiotics, 
or the development of drug dependency or drug abuse.)
Change #6 – Vital signs (Section 9.6.7) 
Systolic and diastolic blood pressure and pulse rate will be measured 15 minutes prior to 
dosing (with a ±5 minutes window) in a sitting position at entry Week 0, every 12 weeks 
starting at Week 14, and at the Completion/ET, Unscheduled, and SFU Visits.
Has been changed to:
Systolic and diastolic blood pressure and pulse rate will be measured 15 minutes prior to 
dosing (with a ±5 minutes window) in a sitting position at entry Week 0, Visit 2, every 
12 weeks starting at Week 14, and at the Completion/ET, Unscheduled, and SFU Visits.
REDACTED 
nd pul
nd pul
n a si
n a si
COPY 
rea
e
abuse.
abuse
This document cannot be used to suppor
wind
wind
ek 14, a
k 14
any
essure
essur
dow
do
marketing
itting
itting
etion/E
etion/E
authorization 
se rat
e rat
application
requi
requ
as that 
s that
ent wi
ent w
)
and 
i
any 
ma
m
to pre
to pr
extensions 
may j
ay
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 89 of 119
17.8
Protocol Amendment 2
Rationale for the amendment
 the decision was made to stop C87035 after 
determining it was inadequate to address the efficacy of CZP for labeling in pediatric 
subjects. CR0012 was amended to allow subjects ongoing in C87035 to enter CR0012 
without having completed C87035, and for treatment in CR0012 to be continued until a 
subject reached the age of 18 years or CZP is approved for use in the US by pediatric subjects 
with CD. 
Additional updates were made to reflect the current UCB contacts, regulatory status of CZP, 
subject exposure, and to comply with the updated UCB definition of AEs of interest.
The format and style of the document was changed to comply with UCB’s new 
document-authoring software; these changes are not specifically noted.
Specific changes:
1. Cover page
Old text:
PROTOCOL CR0012
AN OPEN-LABEL, MULTICENTER STUDY TO ASSESS THE 
SAFETY OF CERTOLIZUMAB PEGOL IN CHILDREN AND 
ADOLESCENTS WITH ACTIVE CROHN’S DISEASE WHO 
COMPLETED C87035 
PHASE 2B
IND Number: 11197
Sponsor:
SCHWARZ BIOSCIENCES, INC.
A Member of the UCB Group of Companies
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
REDACTED 
L C
L
CENT
ENT
ZUM
ZUM
A
COPY 
CR
C
This document cannot be used to support any marketing 
MA
ACT
ACTIV
IV
MPL
MPL
authorization 
R00
R00
TER
TER
AB
AB
application and any extensions 
of CZP
of CZP
st.t.
w 
or variations 
ts
thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 90 of 119
Protocol/Amendment Number
Date
Type of amendment
Final Protocol
07 May 2010
N/A
Amendment 1
29 Jun 2010
Substantial
New text:
PROTOCOL CR0012
AN OPEN-LABEL, MULTICENTER STUDY TO ASSESS THE 
SAFETY OF CERTOLIZUMAB PEGOL IN CHILDREN AND 
ADOLESCENTS WITH ACTIVE CROHN’S DISEASE WHO 
COMPLETED C87035 OR WERE TERMINATED FROM 
C87035 WHEN THE STUDY WAS STOPPED BY UCB
PHASE 2B
IND Number: 11197
Sponsor:
UCB BIOSCIENCES, INC.
A Member of the UCB Group of Companies
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
Protocol/Amendment Number
Date
Type of amendment
Final Protocol
07 May 2010
N/A
Amendment 1
29 Jun 2010
Substantial
Amendment 2
08 May 2012
Substantial
REDACTED
mber: 
mber:
Spon
Spon
COPY 
This document 
nt
en cannot
Pro
Pro
Ame
Ame
n
be 
oto
ot
e used 
mend
men
ed to support any
801
80
marketing 
BIOSC
BIOS
r of the
of th
ma
authorization 
11197
1197
nsor:
sor:
application 
PE
and 
TE
ED 
ED
any
AS
AS
ED
ED
extensions 
S TH
TH
EN A
SE
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 91 of 119
2. Page 2, Sponsor declaration
Old text:
New text:
Clinical Project Manager
_____________________________
Date/Signature
Clinical Trial Biostatistician
 PhD
_____________________________
Date/Signature
Study Physician
, MD
_____________________________
Date/Signature
Clinical Program Director 
, DVM
_____________________________
Date/Signature
REDACTE
TED OP
COPY 
This document 
Cl
Cl
canno
not be
ysic
sic
be used 
icia
cia
to support 
stician
ticia
any marketing authoriz
n
rization 
ation 
ap
applicati
and
and ny 
ny
any exten
ens
n
s
ns 
nsion
tens
or variations 
v
thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 92 of 119
3. Page 3, Study contact information
Old text:
Sponsor
SCHWARZ BIOSCIENCES, INC.
A Member of the UCB Group of Companies
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
Principal/Coordinating Investigator
Sponsor Study Physician
Name:
, MD
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Clinical Project Manager
Name:
, MS
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Clinical Study Biostatistician 
Name:
, MS
Address:
208 Bath Road
Slough, Berkshire, SL1 3WE, UK
Phone:
Fax:
REDACTED 
ED
AC
COPY 
CO
This document 
nt cannot 
ame:
me:
ot
Add
Add
an
be
Stud
Stu
used 
d
to 
to suppo
up
up
up
up
upport
Ralei
ale
or
ppo
any
Arco
Arc
eigh
eigh
ma
o C
marketing 
, M
ke
mark
authorization 
n
za
ho
application 
n
at
and any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 93 of 119
Clinical Monitoring Contract Research Organization
Name:
Kendle International, Inc.
Address:
1200 Carew Tower
441 Vine Street
Cincinnati, Ohio 45202
Phone:
+1 800 733 1572
Fax:
+1 513 381 7684
New text:
UCB BIOSCIENCES, INC.
8010 Arco Corporate Drive
Raleigh, NC  27617
UNITED STATES
Principal/Coordinating Investigator
Sponsor Study Physician
Name:
, MD
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Clinical Project Manager
Name:
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
REDACTED 
, MD
, MD
AC
Corp
Corp
RE
COPY 
This document
F
nt cannot 
Phon
Phon
no
c
be 
s:
used 
d
us
to
Ma
Ma
t
support 
rt
Mana
an
t
ny y
any marketing 
porate 
porate
NC 276
C 27
g
ar
ma
authorization 
tho
a
application and any extensions s or 
o variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 94 of 119
Clinical Study Biostatistician 
Name:
, PhD
Address:
8010 Arco Corporate Drive
Raleigh, NC 27617, USA
Phone:
Fax:
Medical Monitor
Name:
, MD
Address:
5610 Point West Drive
Oakwood, GA 30566
Phone:
Fax:
Clinical Monitoring Contract Research Organization
Name:
PRA International
Address:
Glen Lake 6
4130 Parklake Avenue
Raleigh, NC 27612
Phone:
919-786-8200
Fax:
919-786-8201
4. Section 1, Summary (paragraphs 1 through 6)
Old text:
This is a Phase 2b, open-label, multicenter study to assess the safety of certolizumab pegol 
(CDP870, CZP) in children and adolescents with active Crohn’s disease (CD) who completed 
C87035. 
C87035 was a Phase 2, open-label, multicenter study to assess the safety, efficacy, 
pharmacokinetics (PK), and immunogenicity of CZP in children and adolescents ages 6 to 17 
with moderately to severely active Crohn’s disease. The study was performed as a post 
approval commitment following the Food and Drug Administration (FDA) approval of CZP 
for the treatment of adults with moderately to severely active CD.
Certolizumab pegol, the investigational medicinal product (IMP) is a humanized antibody 
fragment antigen binding (Fab′), with specificity for human tumor necrosis factor alpha 
REDACTED
ch O
ch O
nal
nal
TE
6
ake
ake
DA
COPY 
PY
Or
O
This document
with 
ith 
app
app
cannot 
35 wa
5 wa
rmac
mac
be 
ZP
used
2b, op
2b, op
P) in
P) in
to support 
9
rt
y (p
(par
ar
any 
6
-786-
786-
ny marketing 
e Ave
Aven
NC 2761
C 276
8200
820
ar
authorization 
rgan
rgan
riz
uth
application 
ca
app
and 
an
any extensions 
en
e
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 95 of 119
(TNF), conjugated to polyethylene glycol (PEG). The drug intended for use in this study is 
the liquid formulation of CZP in a prefilled syringe (PFS).
All subjects who complete the Week 62 assessments in C87035 (up to 100 subjects 
anticipated) are eligible to enter this open-label extension study. Following entry, subjects 
may continue on the CZP dose they were receiving at the end of C87035 (Low-Dose Group 
or High-Dose Group [weight adjusted in kg]) every 4 weeks (Q4W) for a 52-week open-label 
Treatment Period. The first clinic visit of this study should coincide with the Week 62 Visit 
of C87035. Home administration of CZP by the subject/caregiver/appropriate designee as 
determined by the Investigator will be permitted following appropriate training at clinic 
visits. A Safety Follow-Up (SFU) Visit will be conducted 12 weeks after the last dose of 
study medication.
If a subject has not been previously reinduced in C87035, the subject is eligible for 
1 reinduction due to loss of response in CR0012 (defined as an increase in Pediatric Crohn’s 
Disease Activity Index [PCDAI] ≥15 points compared to Week 6 of C87035 at 2 consecutive 
visits at least 1 week apart or an overall PCDAI >30 points at any time).
A Data and Safety Monitoring Board (DSMB) will periodically review all emerging safety 
data. Interim analyses will be performed on an annual basis starting from 1 year after the first 
subject’s first visit in CR0012 has occurred.
New text:
This is a Phase 2b, open-label, multicenter study to assess the safety of certolizumab pegol 
(CDP870, CZP) in children and adolescents with active Crohn’s disease (CD) who completed 
C87035 or were terminated from C87035 when the study was stopped by UCB.
C87035 was a Phase 2, open-label, multicenter study to assess the safety, efficacy, 
pharmacokinetics (PK), and immunogenicity of CZP in children and adolescents ages 6 to 17 
with moderately to severely active Crohn’s disease. The study was performed as a 
postapproval commitment following the Food and Drug Administration (FDA) approval of 
CZP for the treatment of adults with moderately to severely active CD. 
 the decision was made to stop C87035 after determining it 
was inadequate to address the efficacy of CZP for labeling in pediatric subjects. 
Subjects ongoing in the study were given the opportunity to enter CR0012 without 
having completed C87035.
Certolizumab pegol, the investigational medicinal product (IMP) is a humanized antibody 
fragment antigen binding (Fab′), with specificity for human tumor necrosis factor alpha 
(TNF), conjugated to polyethylene glycol (PEG). The drug intended for use in this study is 
the liquid formulation of CZP in a prefilled syringe (PFS).
All subjects who complete Week 62 of C87035 or were terminated from C87035 when the 
study was stopped by UCB (and completed all assessments required for 
Week 62/Visit 23 at the time of termination) are eligible to enter this open-label extension 
study. 
Following entry, subjects may continue on the CZP dose they were receiving at the end of 
C87035 (Low-Dose Group or High-Dose Group [weight adjusted in kg]) every 4 weeks 
REDACTED COPY 
udy
udy toto
y
ts with
ts wit
7035 w
7035 w
multic
multic
This document cannot be used to support any marketing authorization application and any extensions or variations thereof.
e of 
of 
le for 
 for 
Pediatr
edi
7035 at
035 a
me).).
review 
eview
arting f
arting
o assess
asses
h activ
h activ
when t
when 
center 
cente
genicit
enicit
Crohn
Crohn
wing th
ing t
ts with
 with
 the 
 the
dress th
ress 
n the st
the s
d C870
d C87
b pegol
pego
antigen
ntige
conjug
conju
iquid f
quid 
All sub
All su
stud
stu
W
po

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 96 of 119
(Q4W) for a 52-week open-label Treatment Period. The first clinic visit of this study 
should coincide with the last visit of C87035 (Week 62/Visit 23). Home administration of 
CZP by the subject/caregiver/appropriate designee as determined by the Investigator will be 
permitted following appropriate training at clinic visits. For subjects performing home 
administration, a phone call to the subject and/or the parents/caregiver will be 
performed by the Investigator (or designee) every 4 weeks between regular clinic visits.
A Safety Follow-Up (SFU) Visit will be conducted 12 weeks after the last dose of study 
medication.
If a subject has not been previously reinduced in C87035, the subject is eligible for 
1 reinduction due to loss of response in CR0012 (defined as an increase in Pediatric Crohn’s 
Disease Activity Index [PCDAI] ≥15 points compared to Week 6 of C87035 at 2 consecutive 
visits at least 1 week apart or an overall PCDAI >30 points at any time).
A Data and Safety Monitoring Board (DSMB) will periodically review all emerging safety 
data. Interim analyses will be performed on an annual basis starting from 1 year after 
the first subject’s first visit in CR0012 has occurred.
5. Section 2, Introduction (paragraph 6 and paragraph 8)
Old text:
Paragraph 6 -
Certolizumab pegol is an engineered, humanized antigen-binding fragment (Fab' fragment) 
conjugated to PEG with specificity for human TNF. Certolizumab pegol (CIMZIA®) has 
been approved in the US and Switzerland for reducing the signs and symptoms of CD and 
maintaining the clinical response in adult subjects with moderately to severely active disease 
who have had an inadequate response to conventional therapy.
Paragraph 8 -
The safety of CZP has been assessed in 2192 adult subjects with CD representing over 
2456 patient years of exposure. Certolizumab pegol is well tolerated. The incidence of 
injection site reactions and hypersensitivity-type reactions was low. There were no reports of 
anaphylaxis or anaphylactoid-type reactions with CZP. All available data in CD show the 
safety of CZP is consistent with the known risks of anti-TNF therapies.
New text:
Paragraph 6-
Certolizumab pegol is an engineered, humanized antigen-binding fragment (Fab' fragment) 
conjugated to PEG with specificity for human TNF. Certolizumab pegol (CIMZIA) has been 
approved in the US, Switzerland, Russia, Brazil, and Chile for reducing the signs and 
symptoms of CD and maintaining the clinical response in adult subjects with moderately to 
severely active disease who have had an inadequate response to conventional therapy.
Paragraph 8-
The safety of CZP has been assessed in 2518 adult subjects with CD representing over 
2837 patient years of exposure. Certolizumab pegol is well tolerated. The incidence of 
REDACTED
ed an
ed a
an TN
an TN
d for re
for r
dult su
ult su
e to c
e to 
COPY 
ntiti
This document
pr
p
sy
symp
mp
y
sev
sev
cannot
uma
ma
ugated
gated
rove
ove
be 
ab
ab
used to 
sis
support
d hy
hype
pe
y
ctoid
ctoid
stent 
stent 
any 
sse
sse
. Cert
 Cer
er
marketing
ubj
conve
conve
ed in
ed i
authorization 
tigen-
gen-b
NF. Ce
F. Ce
educin
ducin
bjects
ects
application and 
 fro
fro
d any
merg
mer
om 
om
a
extensions 
Crohn
Crohn
onsec
onse
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 97 of 119
injection site reactions and hypersensitivity-type reactions was low. There were no reports of 
anaphylaxis or anaphylactoid-type reactions with CZP. All available data in CD show the 
safety of CZP is consistent with the known risks of anti-TNF therapies.
6. Section 3, Study objectives
Old text:
The primary objective of this open-label, multicenter study is to assess the longterm safety 
and tolerability of CZP in children and adolescents with moderately to severely active CD 
who completed C87035. The secondary objectives of this study are to assess the longterm 
efficacy, PK, and immunogenicity of CZP treatment on this population.
New text:
The primary objective of this open-label, multicenter study is to assess the longterm safety 
and tolerability of CZP in children and adolescents with moderately to severely active CD 
who completed C87035 or were terminated from C87035 when the study was stopped by 
UCB. The secondary objectives of this study are to assess the longterm efficacy, PK, and 
immunogenicity of CZP treatment on this population.
7. Section 5.1, Study description (paragraphs 1 through 6)
Old text: 
This is a Phase 2, open-label, multicenter study in children and adolescents with moderately 
to severely active CD who completed C87035 to assess the longterm safety and tolerability of 
CZP. 
All subjects who complete the Week 62 assessments in C87035 are eligible to enter this 
open-label study. Subjects may continue on CZP at the dose they were receiving at the end of 
C87035 (Low-Dose Group or High-Dose Group [weight adjusted in kg; see Section 7.2 and 
Table 7-1]) every 4 weeks for a 52-week open-label Treatment Period. The first clinic visit 
should coincide with the Week 62 visit of C87035. First study drug administration occurs 
2 weeks later (Week 2) and subsequent clinic visits for safety and efficacy assessments are 
scheduled at 12-week intervals. After Week 2, subjects or parents/caregivers/appropriate 
designee as determined by the Investigator have the option of home administration of CZP 
upon appropriate training during a previous clinic visit(s) or continuing to have CZP 
administered every 4 weeks at the clinic. For subjects performing home administration, a 
phone call to the subject and/or the parents/caregiver will be performed by the Investigator 
(or designee) every 4 weeks between regular clinic visits in order to capture potential AEs 
and changes in concomitant medications, and to check compliance with home dosing. An 
SFU Visit will be conducted 12 weeks after the last dose of study medication for subjects.
Please refer to Study Schedule of Assessments in Section 5.2 for visit-specific procedures and 
to Section 5.3 for a schematic representation of the study.
A DSMB will periodically review all emerging safety data (see Section 13.8). Based on the 
safety data, the DSMB can recommend modifying or stopping the study.
Interim analyses will be performed on an annual basis starting from 1 year after the first 
subject’s first visit in CR0012 has occurred.
REDACTED 
in c
in 
35 to a
5 to a
62 ass
62 ass
nue
nue
COPY 
ou
ou
ch
chi
This document
Pleas
leas
to S
to S
cannot
nges
ges
Visit 
Visit
se
se
be
e) ev
e) e
i
used
ery
ry 4
y
he su
he su
to
ainin
aini
4
support 
sub
ub
ervals. 
rvals
d by
by thth
y
ing
ng
any
62 vi
62 v
bseq
bse
marketing 
sess
es
e on CZ
on CZ
Dose G
ose G
-week
week
isi
authorization 
ildren
dren
assess 
sess 
ssm
sm
application 
erm
6)
and
study
tud
m ef
m ef
any
g
erely 
erely
y w
y
extensions 
m
gterm
term
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 98 of 119
Subjects who become ≥18 years during CR0012 may continue in the study at the 
Investigator’s discretion.
New text:
This is a Phase 2, open-label, multicenter study in children and adolescents with moderately
to severely active CD who completed C87035, or were terminated from C87035 when the 
study was stopped by UCB, to assess the longterm safety and tolerability of CZP. 
All subjects who complete Week 62 of C87035 or were terminated from C87035 when 
the study was stopped by UCB (and completed all assessments required for 
Week 62/Visit 23 at the time of termination) are eligible for entry.
All subjects who complete the Week 62 assessments in C87035 are eligible to enter this 
open-label study. Subjects may continue on CZP at the dose they were receiving at the end 
of C87035 (Low-Dose Group or High-Dose Group [weight adjusted in kg; see Section 7.2 
and Table 7-1]) every 4 weeks until the subject reaches the age of 18 years or CZP is 
approved for use in the US by pediatric subjects with CD. The first clinic visit should 
coincide with the last visit of C87035 (Week 62/Visit 23). First study drug administration 
occurs 2 weeks later (Week 2) and subsequent clinic visits for safety and efficacy 
assessments are scheduled at 12-week intervals. After Week 2, subjects or 
parents/caregivers/appropriate designee as determined by the Investigator have the option of 
home administration of CZP upon appropriate training during a previous clinic visit(s) or 
continuing to have CZP administered every 4 weeks at the clinic. For subjects performing 
home administration, a phone call to the subject and/or the parents/caregiver will be 
performed by the Investigator (or designee) every 4 weeks between regular clinic visits in 
order to capture potential AEs and changes in concomitant medications, and to check 
compliance with home dosing. An SFU Visit will be conducted 12 weeks after the last dose 
of study medication for subjects.
Please refer to Study Schedule of Assessments in Section 5.2 for visit-specific procedures and 
to Section 5.3 for a schematic representation of the study.
A DSMB will periodically review all emerging safety data (see Section 13.8). Based on the 
safety data, the DSMB can recommend modifying or stopping the study.
Interim analyses will be performed on an annual basis starting from 1 year after the 
first subject’s first visit in CR0012 has occurred.
Subjects who become ≥18 years during CR0012 may continue in the study at the 
Investigator’s discretion.
8. Section 5.1.1, Study duration per subject
Old text:
The maximum study duration of CZP treatment may be up to 52 weeks. An SFU visit will be 
conducted 12 weeks following the last dose of study drug.
The end of the study is defined as the date of the last SFU visit of the last subject in the study.
week
week
bject a
bject a
ee) ev
ee) ev
anges 
anges 
FU V
FU V
COPY
We
W
ed by
ed by t
y
ning 
ning
k
This document
Old t
ld 
Th
Th
cannot 
ato
to
t
ection
ctio
tete
be 
ho b
o b
or’s
or’s
b
used
irst v
rst v
ed
bec
bec
u
to
will b
will 
to
i
support
y revie
revie
y
can rec
an r
be
b
any
epres
epre
marketing 
in
Visit w
Visit w
Asses
Asse
authorization
durin
durin
s at the
at the
and/or
nd/or
very 4
ry 4
n con
con
application
udy
udy d
y
afet
fety a
y
2, subj
2, sub
the Inv
he In
ng
and 
yea
ea
t clini
clin
d
any
ee S
ee S
ars o
ars 
extensions 
 enter
enter
en
ing at 
ng at 
Se
S
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 99 of 119
New text:
The maximum study duration of CZP treatment may be until the subject reaches the age of 
18 years or CZP is approved for use in the US by pediatric subjects with CD. An SFU 
visit will be conducted 12 weeks following the last dose of study drug.
The end of the study is defined as the date of the last SFU visit of the last subject in the study.
9. Section 5.1.2, Planned number of subjects and sites
Old text:
It is anticipated that the approximately 30 to 40 centers which participated in C87035 will 
participate in this study. Those subjects who completed Week 62 of C87035 may be enrolled 
in this study (up to 100 subjects anticipated).
•
First subject first visit: Jul 2010
•
Last subject first visit: Jan 2013
•
Last subject last visit: Mar 2014 (including the SFU Visit)
New text:
It is anticipated that the approximately 30 to 40 centers which participated in C87035 will 
participate in this study. Those subjects who completed Week 62 of C87035 or were 
terminated from C87035 when the study was stopped by UCB (and completed all 
assessments required for Week 62/Visit 23 at the time of termination) may be enrolled 
in this study.
•
First subject first visit: Jul 2010
•
Last subject first visit: Jun 2012
•
Last subject last visit: to be determined (including the SFU Visit)
REDACTED
s sto
s sto
3 at th
 at th
COPY
rs wh
rs w
pleted 
pleted
opp
op
This document cannot be used to support any marketing 
termin
erm
authorization
d We
We
ped b
ped b
he tim
e tim
application 
ich par
ch pa
eek
eek
and any extensions 
will
will
e enro
enro
or variations thereof.

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 100 of 119
10. Section 5.2, Schedule of  study assessments (Table 5-1)
Old text:
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call 
(home 
administration)
or visit (clinic 
administrationb
Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
6, 10, 18, 22, 
30, 34, 42, 46 
14, 26, 38, 50
52
62
Written informed consent
X
Assessment of inclusion/ exclusion 
criteria
X
Demography
X
Life style
C87035
Crohn’s disease history
C87035
Medical and surgical history
C87035
Assessment of childbearing potential
C87035
X
X
Pregnancy teste
C87035
X
X
X
Physical examination
C87035
X
X
X
TB test
X
TB questionnaire
X
X
X
X
Tanner stage
C87035
X
X
REDACTED
42, 4
42, 
ED
AC
RE
R
COPY 
PY
22, 
2,
46
46
PY
PY
PY
PY
This document cannot 
no
ca
be 
be used 
d
se
to 
C
to support 
rt
7035
035
o
C870
87
up
any 
an marketing 
ng
ke
k
rke
ke
rke
m
authorization 
14
14
tio
za
tho
application 
its
itsb
ap
and 
d
and any extensions 
ex
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 101 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call 
(home 
administration)
or visit (clinic 
administrationb
Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
6, 10, 18, 22, 
30, 34, 42, 46 
14, 26, 38, 50
52
62
Height
C87035
X
X
Weight
C87035
X
X
Vital signsf
C87035
X
X
X
X
X
Adverse eventsa
C87035
X
X
X
X
X
X
Concomitant medicationsa
C87035
X
X
X
X
X
X
Concurrent medical procedures
C87035
X
X
X
X
X
X
PCDAI
C87035
X
X
ESR/hematocrit/albumin for PCDAI
C87035
X
X
CRP
C87035
X
X
Hematology/chemistry/urinalysis
C87035
X
X
X
IMPACT III
C87035
X
X
WPAI:CDg
C87035
X
X
Certolizumab pegol plasma concentrationh
C87035
X
X
X
Anti-CZP antibody plasma concentrationi
C87035
X
X
X
Autoantibodies (ANA and anti-dsDNA)
C87035
X
X
X
Bone markers (osteocalcin, bone specific 
C87035
X
X
X
ED
CT
ED
RE
R
COPY 
Y
PY
CO
This document cannot
ti-dsD
dsD
n, bon
, bon
no
ca
be
ntrati
rat
DN
DN
be used 
ion
onh
d
ion
ion
se
to 
C
to support 
5
rt
7035
035
po
C870
87
su
any 
an marketing 
ing
rke
rk
rk
rk
rk
m
authorization 
n
tio
at
X
hor
X
au
application 
50
50
X
at
X
p
and 
nd
nd
nd
nd
and any
y y 
ermin
rmin
extensions 
letion/
etion/
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 102 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call 
(home 
administration)
or visit (clinic 
administrationb
Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
6, 10, 18, 22, 
30, 34, 42, 46 
14, 26, 38, 50
52
62
alkaline phosphatase, n-telopeptides)
Study drug administrationj
X
X
X
Reinductionk
Loss of response must be confirmed at a clinic visit where assessments and labs are performed to 
determine PCDAI score. Scores cannot be confirmed until lab results are received by central lab a 
few days after the clinic visit. Once loss of response is confirmed, sites must contact the subject to 
return for the first Reinduction Visit.
Reinduction Week 0 (first reinduction dose) is followed by Reinduction Week 2 (second dose, 2 
weeks after first dose), and Reinduction Week 4 (third dose, 2 weeks after second dose). Subjects 
should return to the clinic for each Reinduction. Subject resumes the original schedule of clinic 
visits after reinduction. The clinic should contact the Study Monitor to determine the most 
appropriate way to resume the original schedule of clinic visits.
Reinduction Week 0 assessments: PCDAI: ESR, hematocrit, and albumin; IMPACT-III; 
WPAI:CD
Reinduction Week 2 assessments: PCDAI: ESR, hematocrit, and albumin
Reinduction Week 4 assessments: PCDAI: ESR, hematocrit, and albumin; WPAI:CD
ANA=antinuclear antibody; CRP=C-reactive protein; CZP=certolizumab pegol; dsDNA=double-stranded deoxyribonucleic acid (antibody); 
ESR=erythrocyte sedimentation rate; ET=Early Termination; PCDAI=Pediatric Crohn’s Disease Activity Index; SFU=Safety Follow-Up; TB=tuberculosis; 
WPAI:CD=Work Productivity and Activity Impairment Questionnaire for CD
a.
Week 0 of CR0012 is equivalent to Week 62 (status evaluation) of C87035 with the following exceptions: written informed consent, assessment of 
inclusion/exclusion criteria, demography, TB testing, and TB questionnaire. Ongoing AEs and concomitant medications from C87035 will continue to 
be followed in CR0012. Other assessments will be taken from the C87035 database by UCB.
b.
After Week 2, subjects or parents/caregivers have the option of home administration of CZP upon appropriate training during a previous clinic visit(s) 
REDACTED
s cann
s can
t. Once
t. Once
ction V
tion V
first re
first r
se), an
se), an
cli
cl
CO
d at a 
d at a
no
OPY 
Y
PY
OP
This document
bject
jec
cannot
a, de
a, de
2. Othe
. Othe
cts
cts
be
lent t
ent t
em
em
used
=Ea
Ea
tivity I
vity I
o
to 
e pr
p
arly 
arly
sup
protein
rote
upport
nducti
duct
Reindu
Reind
sup
any 
n W
n W
D
marketing 
d Rei
d Re
nic f
ic for e
or e
f
on. The
n. Th
to resum
o resu
Wee
We
authorization
clinic
clinic
ot be co
be co
e loss o
loss o
Visit.
Visit.
induct
nduct
einin
n application 
50
50
at
X
pl
a
and 
nd
nd
nd
nd
and any
y y 
ermin
rmin
extensions 
letion/
etion/
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 103 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call 
(home 
administration)
or visit (clinic 
administrationb
Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
6, 10, 18, 22, 
30, 34, 42, 46 
14, 26, 38, 50
52
62
or can continue to have CZP administered every 4 weeks at the clinic. For subjects performing home administration, a phone call to the subject and/or 
the parents/caregiver will be performed by the Investigator (or designee) every 4 weeks between regular clinic visits in order to capture potential AEs 
and changes in concomitant medications, and to check compliance with home dosing. Subjects will have the option to either switch to home dosing or 
switch back to site administration at anytime during the study.
c.
Vital signs, concomitant medication, and AEs must be assessed at every Unscheduled Visit. Other safety and PK assessments (eg, CZP plasma sample) 
may be performed at the discretion of the Investigator as related to the nature of the visit.
d.
The SFU Visit should be performed 12 weeks after the final dose of study medication. For subjects continuing directly onto commercial CZP, a SFU 
Visit should be completed prior to the first dose of commercial drug administration.
e.
For all females post menses, a urine pregnancy test will be conducted at all regularly scheduled clinic visits except Week 2.
f.
Vital signs will be collected 15 minutes prior to dosing with a ±5 minute window.
g.
Days missed from school will be assessed using the WPAI:CD for children. The time missed from work will be assessed using the WPAI:CD for 
working individuals with CD. The effect of the child’s CD on the caregiver’s productivity will be assessed using the WPAI:CD for caregivers of 
children with CD.
h.
Plasma samples will be collected to determine the concentration of CZP every 12 weeks starting at Week 14, and at the Completion/Early Termination 
and SFU Visits. Samples will be collected before dosing (except for the Completion/ET and SFU Visits when there is no dosing).
i.
Anti-CZP antibody concentrations in plasma will be collected every 12 weeks starting at Week 14, and at the Completion/ET and SFU Visits (anti-CZP 
antibody measurements will be made using the samples taken for PK measurements at these time points, so additional blood draws will not be required).
j.
If home administration is performed, sufficient study drug will be dispensed at the scheduled every 12-week clinic visit to last until the next scheduled 
REDACTED 
every U
very U
to the
to the
dose
dose
COPY
p
4 wee
4 wee
me dosi
me dosi
This document 
ratio
ati
cannot 
ntrat
trat
s will b
will b
ion i
on i
be 
e
tion
tio
used
o deter
dete
colle
colle
to support 
g the W
g the W
f the chi
the ch
any 
ng with
ng wi
marketing
of stu
of stu
al drug a
al drug
be condu
e cond
authorization
ing. S
ng. S
Unsche
nsche
nature
nature
applicat
rming ho
ming h
ks betw
s betw
Sub
S
ation 
50
50
at
and 
nd
nd
nd
nd
and any
y
ermin
rmin
extensions 
letion/
etion/
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 104 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call 
(home 
administration)
or visit (clinic 
administrationb
Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
6, 10, 18, 22, 
30, 34, 42, 46 
14, 26, 38, 50
52
62
clinic visit.
k.
If a subject has not been previously reinduced in C87035, the subject is eligible for 1 reinduction due to loss of response in CR0012.
REDACTED COPY 
le for 1
le for
This document cannot be used to support any marketing authorization 
1 r
applicat
reindu
eindu
ation 
50
50
at
and 
nd
nd
nd
nd
and any
y y 
ermin
rmin
extensions 
letion/
etion/
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 105 of 119
New text:
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in 
between regular clinic 
visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Written informed consent
X
Assessment of inclusion/ 
exclusion criteria
X
Demography
X
Life style
C87035
Crohn’s disease history
C87035
Medical and surgical history
C87035
Assessment of childbearing 
potential
C87035
X
X
Pregnancy teste
C87035
X
X
X
Physical examination
C87035
X
X
X
TB test
X
TB questionnaire
X
X
X
X
Tanner stage
C87035
X
X
Height
C87035
X
X
Weight
C87035
X
X
Vital signsf
C87035
X
X
X
X
X
ED
CT
ED
R
COPY 
OP
C
This document cannot 
C
no
cann
be
C87
C87
be 
870
7
be used 
d
5
d
035
035
us
to 
t
support t
por
po
po
p
su
any y
a
marketing 
ng
ke
authorization 
za
ori
ho
au
application 
ek 14
k 14
plic
ap
and 
and any
Ear
Ea
Term
Term
extensions 
on
mpleti
pleti
te
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 106 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in 
between regular clinic 
visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Adverse eventsa
C87035
X
X
X
X
X
X
Concomitant medicationsa
C87035
X
X
X
X
X
X
Concurrent medical procedures
C87035
X
X
X
X
X
X
PCDAI
C87035
X
X
ESR/hematocrit/albumin for 
PCDAI
C87035
X
X
CRP
C87035
X
X
Hematology/chemistry/urinalys
is
C87035
X
X
X
IMPACT III
C87035
Xl
X
WPAI:CDg
C87035
Xl
X
Certolizumab pegol plasma 
concentrationh
C87035
X
X
X
Anti-CZP antibody plasma 
concentrationi
C87035
X
X
X
Autoantibodies (ANA and anti-
dsDNA)
C87035
X
X
X
Bone markers (osteocalcin, 
bone specific alkaline 
phosphatase, n-telopeptides)
C87035
Xl
X
REDACTED 
ED
DA
R
COPY 
PY
C
This document cannot
C
ann
be 
e used 
d
035
d to 
t
support t
por
upp
any y
a
marketing 
ng
ar
m
authorization 
on
iza
ori
ut
application 
tio
X
lic
X
ap
and 
and any 
ny extensions 
tion/ 
on/ 
arly
rly
minat
ina
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 107 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in 
between regular clinic 
visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
Study drug administrationj
X
X
X
Reinductionk
Loss of response must be confirmed at a clinic visit where assessments and labs are performed to determine PCDAI score. 
Scores cannot be confirmed until lab results are received by central lab a few days after the clinic visit. Once loss of 
response is confirmed, sites must contact the subject to return for the first Reinduction Visit.
Reinduction Week 0 (first reinduction dose) is followed by Reinduction Week 2 (second dose, 2 weeks after first dose), and 
Reinduction Week 4 (third dose, 2 weeks after second dose). Subjects should return to the clinic for each Reinduction. 
Subject resumes the original schedule of clinic visits after reinduction. The clinic should contact the Study Monitor to 
determine the most appropriate way to resume the original schedule of clinic visits.
Reinduction Week 0 assessments: PCDAI: ESR, hematocrit, and albumin; IMPACT-III; WPAI:CD
Reinduction Week 2 assessments: PCDAI: ESR, hematocrit, and albumin
Reinduction Week 4 assessments: PCDAI: ESR, hematocrit, and albumin; WPAI:CD
ANA=antinuclear antibody; CRP=C-reactive protein; CZP=certolizumab pegol; dsDNA=double-stranded deoxyribonucleic acid (antibody); 
ESR=erythrocyte sedimentation rate; ET=Early Termination; PCDAI=Pediatric Crohn’s Disease Activity Index; SFU=Safety Follow-Up; TB=tuberculosis; 
WPAI:CD=Work Productivity and Activity Impairment Questionnaire for CD
aWeek 0 of CR0012 is equivalent to the last visit (Week 62; status evaluation) of C87035 with the following exceptions: written informed consent, 
assessment of inclusion/exclusion criteria, demography, TB testing, and TB questionnaire. Ongoing AEs and concomitant medications from C87035 will 
continue to be followed in CR0012. Other assessments will be taken from the C87035 database by UCB. Subjects who were terminated from C87035 
when the study was stopped by UCB completed all assessments required for Week 62/Visit 23 at the time of termination.
bAfter Week 2, subjects or parents/caregivers have the option of home administration of CZP upon appropriate training during a previous clinic visit(s) or 
can continue to have CZP administered every 4 weeks at the clinic. For subjects performing home administration, a phone call to the subject and/or the 
parents/caregiver will be performed by the Investigator (or designee) every 4 weeks between regular clinic visits in order to capture potential AEs and 
changes in concomitant medications, and to check compliance with home dosing. Subjects will have the option to either switch to home dosing or switch 
back to site administration at anytime during the study.
cVital signs, concomitant medication, and AEs must be assessed at every Unscheduled Visit. Other safety and PK assessments (eg, CZP plasma sample) may 
owed
owe
second 
second 
ic visits
c visits
ume th
me th
PCDAI
PCDAI
s: PCD
s: PC
COPY 
ssess
sse
by cent
by cen
o return
o return
d b
d b
This document cannot 
tioio
t anytim
anytim
t medi
medi
be
ed by
by
ons, 
ons, 
used
givers
vers
ed eve
d eve
y th
y th
to
plete
plet
h
support
Week
eek 6
raphy, T
aphy,
ssments
sments
ted 
ted
any 
n; P
Questio
Questi
62
mark
ertolizum
tolizu
PCD
PCD
rketing 
: 
DAI: ES
DAI: E
PCDAI:
PCDA
rk
authorization
for th
or th
y Reind
Reind
dose). S
ose). S
s after r
after r
e origin
origin
ESR, 
ESR,
application 
tio
ents and 
nts an
al lab a
al lab a
he f
he
lic
and 
and any 
ny extensions 
tion/ 
on/ 
arly
rly
minat
ina
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 108 of 119
Table 5-1. Schedule of study assessments
Treatment Period
Visit or phone call 
(+/-7 days)
Entry a
Visit
Phone call (home 
administration)or visit 
(clinic administrationb
Regular Clinic Visitsb
Completion/ 
Early 
Termination
Unscheduled 
Visitc
SFUd
Week
0
2
Every 4 weeks beginning 
at Week 6 and in 
between regular clinic 
visits
Every 12 weeks 
beginning at Week 14
+12 weeks 
after last 
dose of 
study drug
be performed at the discretion of the Investigator as related to the nature of the visit.
dThe SFU Visit should be performed 12 weeks after the final dose of study medication. For subjects continuing directly onto commercial CZP, a SFU Visit 
should be completed prior to the first dose of commercial drug administration.
eFor all females post menses, a urine pregnancy test will be conducted at all regularly scheduled clinic visits except Week 2.
fVital signs will be collected 15 minutes prior to dosing with a ±5 minute window.
gDays missed from school will be assessed using the WPAI:CD for children. The time missed from work will be assessed using the WPAI:CD for working 
individuals with CD. The effect of the child’s CD on the caregiver’s productivity will be assessed using the WPAI:CD for caregivers of children with CD.
hPlasma samples will be collected to determine the concentration of CZP every 12 weeks starting at Week 14, and at the Completion/Early Termination and 
SFU Visits. Samples will be collected before dosing (except for the Completion/ET and SFU Visits when there is no dosing).
iAnti-CZP antibody concentrations in plasma will be collected every 12 weeks starting at Week 14, and at the Completion/ET and SFU Visits (anti-CZP 
antibody measurements will be made using the samples taken for PK measurements at these time points, so additional blood draws will not be required).
jIf home administration is performed, sufficient study drug will be dispensed at the scheduled every 12-week clinic visit to last until the next scheduled clinic 
visit.
kIf a subject has not been previously reinduced in C87035, the subject is eligible for 1 reinduction due to loss of response in CR0012.
lMeasured at Weeks 14, 26, 38, 50 and then every 12 months thereafter.
REDACTED
g
window
window
ldren. T
dren. 
prod
produc
uc
n of CZ
n of CZ
he
he
COPY 
n. Fo
n. F
ularly 
ularly 
This document cannot be used to support 
C87035,
8703
y 12 m
12 mon
on
any
 will 
wil
marketing 
ZP ev
ev
Comple
Comple
very 12
ery 12
for PK
for PK
b
authorization
sched
sched
The tim
The tim
ctivity
tivity
ver
ver
applicatio
subjects
bject
tion 
tio
and 
and any 
ny extensions 
tion/ 
on/ 
arly
rly
minat
ina
io
or 
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 109 of 119
11. Section 5.3, Schematic diagram (figure)
Old text:
New text:
ED 
ACTED
REDA
R
OPY 
CO
This document cannot be used
ed to 
ort 
suppo
s
ny 
any
ng 
arketing
mar
n
zation 
thoriza
auth
on 
lication
applic
a
d
and any 
s
nsions 
extens
e
or variations 
on thereof.
08
08 M

UCB
08 May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 110 of 119
CZP=certolizumab pegol; Q4W=every 4 weeks
COPY 
This document cannot be used to support any marketi
eting authorization application and 
y 
any extensions or variations 
on thereof.
08
08 M

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 111 of 119
12. Section 5.4, Rational for study design and selection of dose
Old text:
Following the Food and Drug Administration (FDA) approval of CZP for the treatment of 
CD in adults, C87035 was a postapproval commitment to investigate the administration of 
CZP administration in children and adolescents with moderately to severely active CD. This 
study will provide continued treatment of CZP to subjects who completed C87035 and who, 
in the Investigator’s opinion, would benefit from continued administration of CZP.
The primary objective of this open-label study is to assess the longterm safety and tolerability 
of CZP in children and adolescents with moderately to severely active CD who completed 
C87035. The secondary objectives of this study are to assess the longterm efficacy, PK, and 
immunogenicity of CZP treatment on this population. Subjects may continue on CZP at the 
dose they were receiving at the end of C87035.
New text:
Following the Food and Drug Administration (FDA) approval of CZP for the treatment of 
CD in adults, C87035 was a postapproval commitment to investigate the administration of 
CZP administration in children and adolescents with moderately to severely active CD. This 
study will provide continued treatment of CZP to subjects who completed C87035 or were 
terminated from C87035 when the study was stopped by UCB and who, in the 
Investigator’s opinion, would benefit from continued administration of CZP.
The primary objective of this open-label study is to assess the longterm safety and tolerability 
of CZP in children and adolescents with moderately to severely active CD who completed 
C87035 or were terminated from C87035 when the study was stopped by UCB. The 
secondary objectives of this study are to assess the longterm efficacy, PK, and 
immunogenicity of CZP treatment on this population. Subjects may continue on CZP at the 
dose they were receiving at the end of C87035.
13. Section 6.1, Inclusion criteria (item #3)
Old text:
3.
Subject completed the C87035 study (Week 62 Visit).
New text:
3.
Subject completed the C87035 study (Week 62 Visit) or was terminated from 
C87035 when the study was stopped by UCB and completed all assessments 
required for Week 62/Visit 23 at the time of termination.
REDACTED
s s
s sto
to
continu
continu
l study
 study
with m
with m
87
87
COPY
to
mode
mod
subjec
subjec
op
This document cannot
j
C870
C870
req
req
be
ect c
ect c
used 
plp
to
lete
lete
support
crite
crite
d
any
end o
end 
marketing
moder
de
7035 w
035 w
e to ass
 to as
on thi
on th
f
au
y
thorization
cts w
ts w
pped b
ped b
ued ad
ued ad
is to
is to
y
era
era
application 
f CZP 
CZP
estigat
estiga
ratel
ately
who
h
and any
e on
e on
extensions 
olerab
lerab
omple
omple
cacy
acy P
n C
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 112 of 119
14. Section 6.2, Exclusion criteria (item #1)
Old text:
1.
Subject did not complete the C87035 study (Week 62 Visit).
New text:
1.
Subject did not complete the C87035 study (Week 62 Visit) or was terminated from 
C87035 when the study was stopped by UCB but did not complete all assessments 
required for Week 62/Visit 23 at the time of termination.
15. Section 7.7, Procedures for monitoring and subject compliance (final paragraph)
Old text:
If a subject is found to be persistently noncompliant (missing 2 or more consecutive 
scheduled IMP doses or missing 3 or more doses over the 52-week Treatment Period), the 
Sponsor in conjunction with the Investigator will make a decision as to whether the subject 
should be withdrawn from the study.
New text:
If a subject is found to be persistently noncompliant (missing 2 or more consecutive 
scheduled IMP doses or missing 3 or more doses over the 52-week Treatment Period), the 
Sponsor in conjunction with the Investigator will make a decision as to whether the subject 
should be withdrawn from the study.
16. Section 8.1, Entry Week 0
New text added at the beginning:
Week 0 of CR0012 is equivalent to Week 62 of C87035 with the exceptions noted below. 
Subjects who were terminated from C87035 when the study was stopped by UCB 
completed all assessments required for Week 62/Visit 23 at the time of termination.
17. Section 8.2, Week 2 Visit (final bullet)
Old text:
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing (for Weeks 6 and 10)
New text:
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing (for Weeks 6 and 10)
REDACTED 
W
COPY 
miss
mis
er the
er the
OPY
make
make
This document cannot 
ens
ns
vestiga
estiga
be 
sing
sing
used 
f ap
f a
to
ug
appr
appr
support 
it 
g to s
to s
any 
(fina
(fina
marketing 
Week
eek 62
6
m C87
m C8
red fo
ed f
authorization
e a de
e a de
application 
g 2 or m
2 or 
52
52-w
ap
i
and
whe
whe
any
ent Pe
ent P
ethe
eth
extensions 
aph)
ph)
cutive
utive
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 113 of 119
18. Section 8.3 (section heading text)
Old text:
Phone call (home administration) or visit (clinic administration) (Weeks 6, 10, 18, 22, 30, 34, 
42, 46)
New text:
Phone call (home administration) or visit (clinic administration) (every 4 weeks and in 
between regular clinic visits beginning at Week 6)
19. Section 8.4 (section heading text and content)
Old text:
8.4
Weeks 14, 26, 38, 50 Visits
•
Assessment of childbearing potential (female subjects only)
•
Urine pregnancy test (female subjects of childbearing potential only)
•
Physical examination
•
TB questionnaire
•
Tanner stage
•
Weight and height
•
Vital signs
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
PCDAI
•
ESR/hematocrit/albumin for PCDAI
•
CRP
•
Hematology, clinical chemistry, and urinalysis
•
IMPACT III
•
WPAI:CD (for children, for working individuals with CD and for caregivers)
•
Certolizumab pegol plasma concentration
•
Anti-CZP antibody plasma concentration
•
Autoantibody concentrations (ANA and anti-dsDNA)
•
Bone markers (osteocalcin, bone specific alkaline phosphatase, n-telopeptides)
•
Study drug administration (including training and self-injection under supervision, as 
appropriate)
REDACTED COPY 
This document
•
A
•
cannot
AI:C
:C
Certol
erto
A
be 
CD
CD
used
clin
lin
IIIII
to 
nic
nic
support
min for
n fo
any marketing 
s
authorization application and 
ly)
y)
any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 114 of 119
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing:
−
Week 14 (for Weeks 18 and 22)
−
Week 26 (for Weeks 30 and 34)
−
Week 38 (for Weeks 42 and 46)
New text:
8.4
Regular clinic visits 
8.4.1 Assessments every 12 weeks beginning at Week 14
•
Assessment of childbearing potential (female subjects only)
•
Urine pregnancy test (female subjects of childbearing potential only)
•
Physical examination
•
TB questionnaire
•
Tanner stage
•
Weight and height
•
Vital signs
•
Adverse events
•
Concomitant medications
•
Concurrent medical procedures
•
PCDAI
•
ESR/hematocrit/albumin for PCDAI
•
CRP
•
Hematology, clinical chemistry, and urinalysis
•
IMPACT III
•
WPAI:CD (for children, for working individuals with CD and for caregivers)
•
Certolizumab pegol plasma concentration
•
Anti-CZP antibody plasma concentration
•
Autoantibody concentrations (ANA and anti-dsDNA)
•
Bone markers (osteocalcin, bone specific alkaline phosphatase, n-telopeptides)
•
Study drug administration (including training and self-injection under supervision, as 
appropriate)
REDACTED COPY 
This document
•
A
•
cannot
olizu
lizu
Anti-
nti-C
be 
CD
um
um
used 
D (fo
D (fo
u
to support 
cal ch
al ch
any 
or PCD
or PC
marketing authorization application and any extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 115 of 119
•
Dispensing of drug to subject/caregiver/appropriate designee as determined by the 
Investigator, if appropriate for home dosing
−
Week 14 (for Weeks 18 and 22)
−
Week 26 (for Weeks 30 and 34)
−
Week 38 (for Weeks 42 and 46)
•
8.4.2
Assessments at Weeks 14, 26, 38, 50 and then every 12 months thereafter:
−
IMPACT III
−
WPAI:CD (for children, for working individuals with CD, and for caregivers)
−
Bone markers (osteocalcin, bone specific alkaline phosphatase, n-telopeptides)
20. Section 8.5 (section heading text)
Old text:
Completion (Week 52)/Early Termination Visit
New text:
Completion/Early Termination Visit
21. Section 9.3 (section heading test and bullet list)
Old text:
Section heading-
Adverse events of special interest
Bullet list-
•
Infections including serious opportunistic infections
•
Malignancies including lymphoma and leukemia
•
Congestive heart failure
•
Demylinating-like disorders
•
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
•
Serious bleeding events
•
Lupus and lupus-like syndrome
•
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
New text:
Section heading-
Adverse events of interest
REDACTED 
t
COPY 
list)
ist)
This document
e
cannot
pus an
us an
Serio
Serio
be
blee
le
d
used
emia, 
mia,
eed
eed
to 
e 
support 
ym
y
ure
ure
diso
diso
any 
p
mpho
mpho
marketing 
portu
portu
authorization application and any extensions 
givers
ivers
lopep
opep
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 116 of 119
Bullet list-
•
Serious infections including opportunistic infections
•
Malignancies including lymphoma 
•
Congestive heart failure
•
Demylinating-like disorders
•
Aplastic anemia, pancytopenia, thrombocytopenia, neutropenia, and leucopenia
•
Serious bleeding events
•
Lupus and lupus-like illness
•
Serious skin reactions (eg, Stevens Johnson Syndrome, toxic epidermal necrosis, and 
erythema multiforme)
22. Section 9.4, Immediate reporting of adverse events (last bullet)
Old text:
•
AE of special interest (see Section 9.3)
New Text:
•
AE of special interest (see Section 9.3)
23. Section 10.4.1, Bone markers
Old text:
Markers of bone and collagen turnover, reflecting the childhood growth curve, will be 
measured every 12 weeks starting at Week 14, and at the Completion/ET Visit. These 
markers will include: osteocalcin, bone specific alkaline phosphatase, and n-telopeptides. 
Tests will be performed by a central laboratory facility.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
New text:
Markers of bone and collagen turnover, reflecting the childhood growth curve, will be 
measured at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and at the 
Completion/ET Visit. These markers will include: osteocalcin, bone specific alkaline 
phosphatase, and n-telopeptides. Tests will be performed by a central laboratory facility.
Instructions on blood sample collection, processing, storage, and shipping will be provided in 
the laboratory manual for this study.
REDACTED COPY 
This document
Instru
nstru
the
th
cannot 
a
letion/
etion/
sphat
sphat
be 
bon
atat W
used 
ne a
ne a
to 
al 
support
a cen
ce
ample c
mple 
for th
for th
any
in, bo
n, b
entr
ent
marketing 
ver, ref
er, re
at We
at W
authorization application 
et)
and 
)
any extensions 
crosis
rosis
or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 117 of 119
24. Section 10.7, IMPACT-III (first paragraph)
Old text:
The IMPACT questionnaire is a disease-specific health-related quality of life (HRQOL) 
questionnaire for use in children with IBD that was originally developed and validated by a 
Canadian team (Griffiths et al, 1999; Otley et al, 2002). The IMPACT-III, a modified version 
of the original questionnaire, contains 35 questions assessing the following 6 domains: bowel 
symptoms, systemic symptoms, emotional functioning, social functioning, body image, and 
treatment/interventions. For each question, there are 5 Likert response options. Total 
IMPACT-III scores range from 35 to 185 with higher scores indicating better HRQOL. This 
questionnaire will be used to assess HRQOL of all subjects; however, it has only been 
validated for children aged ≥10 years in North America. The IMPACT-III questionnaire is 
provided in Section 17.3. The IMPACT-III questionnaire will be administered every 
12 weeks starting at Week 14, and at the Completion /ET Visit. 
New text:
The IMPACT questionnaire is a disease-specific health-related quality of life (HRQOL) 
questionnaire for use in children with IBD that was originally developed and validated by a 
Canadian team (Griffiths et al, 1999; Otley et al, 2002). The IMPACT-III, a modified version 
of the original questionnaire, contains 35 questions assessing the following 6 domains: bowel 
symptoms, systemic symptoms, emotional functioning, social functioning, body image, and 
treatment/interventions. For each question, there are 5 Likert response options. Total 
IMPACT-III scores range from 35 to 185 with higher scores indicating better HRQOL. This 
questionnaire will be used to assess HRQOL of all subjects; however, it has only been 
validated for children aged ≥10 years in North America. The IMPACT-III questionnaire is 
provided in Section 17.3. The IMPACT-III questionnaire will be administered at Weeks 14, 
26, 38, 50 and then every 12 months thereafter and at the Completion /ET Visit. 
25. Section 10.8, Days missed from school/work (WPAI:CD for children and for 
working individuals with CD) (paragraph 4)
Old text:
The WPAI:CD for children questionnaire is administered to all subjects or the 
parent(s)/legally acceptable representative(s) and the WPAI:CD for working individuals 
questionnaire is only administered to subjects who work, under supervision of the 
Investigator or designee every 12 weeks starting at Week 14, and at the Completion /ET 
Visit. 
New text:
The WPAI:CD for children questionnaire is administered to all subjects or the 
parent(s)/legally acceptable representative(s) and the WPAI:CD for working individuals 
questionnaire is only administered to subjects who work, under supervision of the 
Investigator or designee at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and 
at the Completion /ET Visit. 
REDACTED
re ar
re ar
with hig
ith hig
QOL o
QOL o
in No
n No
CT
CT
COPY
 T
assessi
assess
ning,
ning
This document 
he
paren
paren
qu
qu
cannot 
ext:
xt:
 WP
WP
be used
only
only
r desi
desi
to
cept
cept
support 
ldren q
dren q
tab
any
CD) 
CD)
marketing 
rth
III que
III qu
s there
ther
m sch
m sc
authorization
, soci
, soci
 5 Lik
5 Lik
gher s
her s
of all s
f all s
h Am
h A
application
ality
ity o
y
evelop
velop
IMPAC
MPA
ng the
ng th
al
and any extensions
. Thi
Th
en
onnair
onnair
every
ever
or 
i
variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 118 of 119
26. Section 10.9, Effect on the caregiver's work (WPAI:CD for caregivers) 
(paragraph 2)
Old text:
The questionnaire is administered under supervision of the Investigator or designee to the 
caregiver every 12 weeks starting at Week 14, and at the Completion/ET Visit.
New text:
The questionnaire is administered under supervision of the Investigator or designee to the 
caregiver at Weeks 14, 26, 38, 50 and then every 12 months thereafter, and at the 
Completion/ET Visit.
27. Section 13.8, Planned interim analysis and data monitoring 
Old text:
A DSMB will review safety data. The DSMB members will be independent of the Sponsor 
and Investigators. The DSMB members will be informed by GCSP (or designee) of all SAEs 
at the time of expedited reporting and will review periodically all emerging safety data 
(SAEs, AEs, safety laboratory data). Based on the safety data, the DSMB can recommend 
modifying/stopping the study.
In order to assess the continuing longterm safety and efficacy of CZP, interim analyses will 
be performed on an annual basis starting from 1 year after the first subject’s first visit in 
CR0012 has occurred. The analyses will include all variables collected during the relevant 
period for all subjects included in the study at the time of the analysis. As no sample size 
calculation was performed, no formal statistical testing will be carried out and, thus, no 
adjustment to any significance level needs to be considered.
Should a regulatory authority request an additional interim analysis for a time other than as 
stated above, this will be performed according to the request.
New text:
A DSMB will review safety data. The DSMB members will be independent of the Sponsor 
and Investigators. The DSMB members will be informed by GCSP (or designee) of all SAEs 
at the time of expedited reporting and will review periodically all emerging safety data 
(SAEs, AEs, safety laboratory data). Based on the safety data, the DSMB can recommend 
modifying/stopping the study.
In order to assess the continuing longterm safety and efficacy of CZP, interim analyses 
will be performed on an annual basis starting from 1 year after the first subject’s first 
visit in CR0012 has occurred. The analyses will include all variables collected during the 
relevant period for all subjects included in the study at the time of the analysis. As no 
sample size calculation was performed, no formal statistical testing will be carried out 
and, thus, no adjustment to any significance level needs to be considered.
No interim analyses are planned. Should a regulatory authority request an additional 
interim analysis for a time other than as stated above, this will be performed according to 
the request.
REDACTED
1 yea
1 ye
lude a
ude a
dy at th
at th
y
statisti
statist
needs
need
COPY 
nd eff
nd ef
ear
ear
This document
elev
lev
t
sam
sam
me
a
cannot
perf
perf
o
t in C
in C
an
van
va
c
be
o ass
o ass
be used
ety l
y l
pping
ping
to 
ited
ited
lab
lab
support
etyty dat
dat
y
DSMB
DSM
d rep
d re
any marketing
ds to b
s to b
t an add
an ad
d acco
d acc
authorization
ficac
icac
afafter 
ter
f
all vari
l vari
he tim
he tim
cal te
al te
application
or
emerg
emer
the DS
the D
cy
cy o
y
and
dent
en
r des
des
any 
nt of
nt o
extensions or variations thereof.

UCB
08  May 2012
Clinical Study Protocol
Certolizumab pegol
CR0012
Confidential
Page 119 of 119
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 
__
__
COPY 
This document cannot be used to support any marketing authorization 
____
____
Date/
Date
application and 
eem
em
any 
ment
men
extensions 
will be
ill be
ior 
or 
or variations thereof.