POST-MARKETING OBSERVATIONAL COHORT STUDY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD) TREATED WITH CT-P13 IN USUAL CLINICAL PRACTICE (CONNECT-IBD)
Conditions: Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn's Disease
Sponsor: Pfizer

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 1 of 56
NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Post Authorization Safety Study (PASS) information
Title
Post-Marketing Observational Cohort Study of 
Patients with Inflammatory Bowel Disease (IBD) 
Treated with CT-P13 in Usual Clinical Practice 
(CONNECT-IBD)
Protocol number
C1231001
(Hospira Protocol ZOB INF 1402)
Protocol version identifier
Version 3.0
Date of last version of protocol
23 February 2015
EU Post Authorisation Study (PAS) 
register number
To be determined
Active substance
Infliximab
Medicinal product
CT-P13, Remicade
Product reference
CT-P13: EMEA/H/C/002778
Remicade: EMEA/H/C/002576
Procedure number
Not applicable
Research question and objectives
Primary study objectives:

To characterise the population and drug 
utilisation patterns of patients treated with 
CT-P13 for Crohn’s Disease (CD) or 
Ulcerative Colitis (UC) in the context of 
standard of care Remicade

To explore the long-term safety profile of 
CT-P13 in the treatment of patients with CD or 
UC in the context of standard of care 
Remicade
Secondary study objective: 

To assess the effectiveness of CT-P13 in the 
treatment of patients with CD or UC in the 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 2 of 56
context of standard of care Remicade
Author
Pfizer Inc.
PPD
PPD
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 3 of 56
TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS................................................................................................5
2. RESPONSIBLE PARTIES....................................................................................................7
3. ABSTRACT...........................................................................................................................8
4. AMENDMENTS AND UPDATES.....................................................................................13
5. MILESTONES.....................................................................................................................17
6. RATIONALE AND BACKGROUND................................................................................17
7. RESEARCH QUESTION AND OBJECTIVES .................................................................19
7.1. Primary Study Objective .........................................................................................19
7.2. Secondary Study Objective .....................................................................................19
8. RESEARCH METHODS ....................................................................................................19
8.1. Study Design ...........................................................................................................19
8.2. Setting......................................................................................................................22
8.2.1. Inclusion Criteria ........................................................................................22
8.2.2. Exclusion Criteria.......................................................................................22
8.2.3. Regions/Number of Study Sites..................................................................22
8.2.4. Enrolment ...................................................................................................22
8.2.5. Patient Eligibility........................................................................................23
8.3. Variables..................................................................................................................23
8.3.1. Primary Outcomes Variables......................................................................23
8.3.2. Secondary Outcomes Variables..................................................................24
8.4. Data Sources............................................................................................................24
8.5. Study Size................................................................................................................28
8.6. Data Management ...................................................................................................29
8.6.1. Electronic Data Capture (EDC) System .....................................................29
8.6.2. Data Entry...................................................................................................29
8.6.3. Statistical Software.....................................................................................29
8.7. Data Analysis ..........................................................................................................29
8.8. Quality Control........................................................................................................30
8.8.1. Site Training and Initiation.........................................................................30
CCI
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 4 of 56
8.8.2. Site Monitoring...........................................................................................30
8.9. Strengths and Limitations of the Research Methods...............................................31
8.9.1. Lost to Follow-up .......................................................................................31
8.9.2. Study Limitations........................................................................................31
8.10. Other aspects .........................................................................................................32
8.10.1. National Leaders Committee....................................................................32
8.10.2. Concomitant Medication Use ...................................................................32
8.10.3. Regulatory Authorities..............................................................................32
8.10.4. Protocol Modifications .............................................................................32
8.10.5. Compensation to Investigators .................................................................33
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................33
9.1. Patient Information and Consent.............................................................................33
9.2. Patient Withdrawal..................................................................................................33
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............34
9.4. Ethical Conduct of the Study ..................................................................................34
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................34
10.1. Single Reference Safety Document.......................................................................43
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........44
11.1. Reporting to Regulatory Agencies ........................................................................44
11.2. Use of Information and Publications.....................................................................44
12. REFERENCES ..................................................................................................................45
13. LIST OF TABLES.............................................................................................................46
14. LIST OF FIGURES ...........................................................................................................46
APPENDICES .........................................................................................................................47

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 5 of 56
1. LIST OF ABBREVIATIONS
Abbreviation
Definition
ADA
Anti-Drug Antibody
AE
Adverse Event
AEM
Adverse Event Monitoring
AESI
Adverse Event of Special Interest
ARDS
Acute Respiratory Distress Syndrome
AV
Atrioventricular
CD
Crohn’s Disease
CIOMS
Council for International Organizations of Medical Sciences
CRF
Case Report Form 
SR
Study Report
DIC
Disseminated Intravascular Coagulation
DVT
Deep Vein Thrombosis
EDC
Electronic Data Capture 
EMA
European Medicines Agency
E-mail
Electronic mail
ENCePP
European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance
FSFV
First Subject First Visit
GEP
Good Epidemiological Practice
GI
Gastrointestinal
GPP
Guidelines for Good Pharmacoepidemiology Practices
GVP
Good Pharmacovigilance Practices
HBI
Harvey Bradshaw Index
HBV
Hepatitis B Virus
HCP
Healthcare provider
HSTCL
Hepatosplenic T-cell Lymphoma
IBD
Inflammatory Bowel Disease
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
ICMJE
International Committee of Medical Journal Editors
ID
Identification
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 6 of 56
Abbreviation
Definition
IEA
International Epidemiological Association
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISPE
International Society for Pharmacoepidemiology
ISPOR
International Society for Pharmacoeconomics and Outcomes Research
KOL
Key Opinion Leader
LSLV
Last Subject Last Visit
mAb
Monoclonal Antibody
MAH
Marketing Authorisation Holder
NI
Non-Interventional
NIS
Non-Interventional Study
NISL
Non-Interventional Study Lead
PASS
Post Authorization Safety Study
PRCA
Pure Red Cell Aplasia
RA
Rheumatoid Arthritis
RCT
Randomised Clinical Trial
RMP
Risk Management Plan
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SIDS
Sudden Infant Death Syndrome
SmPC
Summary of Product Characteristics
SOC
Standard of Care
TNF
Tumour Necrosis Factor
UC
Ulcerative Colitis
CCI
CCI
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 7 of 56
2. RESPONSIBLE PARTIES
The Pfizer Non-Interventional Study Lead (NISL) for this study protocol is 
 
.
The table below enlists all the National Leaders of the respective participating countries in 
the study. 
Please refer the Appendix 1 of this protocol, which indicates that a list of site Investigators 
are maintained in a stand-alone document.
PPD
PPD

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 8 of 56
3. ABSTRACT
Protocol Title
Post-Marketing Observational Cohort Study of Patients with Inflammatory Bowel Disease 
Treated with CT-P13 (infliximab) in Usual Clinical Practice (CONNECT-IBD).
Protocol Amendment version 3.0 dated 25-Aug-2017
Rationale and Background
Remicade (infliximab, Janssen Biotech, Inc.), an IgG1 chimeric human-murine monoclonal 
antibody (mAb), is a centrally authorised product approved in the European Union in 
August 1999.  Since then it has been utilised in many thousands of patients for the treatment 
of 2 major types of inflammatory bowel disease (IBD), Crohn’s Disease (CD) and ulcerative 
colitis (UC).  In September 2013, CT-P13 (infliximab), a mAb biosimilar to reference 
Remicade, was approved by the European Medicines Agency (EMA) based on an extensive 
biosimilar comparability exercise, which demonstrated that quality, as well as the clinical 
efficacy, pharmacokinetics and safety profile of CT-P13 are highly comparable to that of 
Remicade.  Marketing authorisation of CT-P13 included all approved indications for 
Remicade including the extrapolated indications of moderate to severe CD and UC.  This 
study is designed to characterise the patient population currently receiving CT-P13 in the 
context of standard of care (SOC) utilisation of Remicade, and to document the safety and 
effectiveness of CT-P13, also in the context of SOC Remicade, in the treatment of patients 
with CD or UC in real-world clinical practice. 
Research Question and Objectives
Primary study objectives:

To characterise the population and drug utilisation patterns of patients treated with 
CT-P13 for CD or UC in the context of SOC Remicade.

To explore the long-term safety profile of CT-P13 in the treatment of patients with 
CD or UC in the context of SOC Remicade.
Secondary study objective: 

To assess the effectiveness1 of CT-P13 in the treatment of patients with CD or UC in 
the context of SOC Remicade.
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 9 of 56
Study Design
This study is a multi-national, multi-centre, observational cohort study of patients with CD or 
UC, who are treated with CT-P13 or Remicade for the smaller SOC cohort.  The decision to 
treat with CT-P13 or Remicade will be made at the usual care discretion of the physician 
independent of and before the decision to enrol patients in the study.  In order to characterise 
the population and drug utilisation patterns associated with the use of CT-P13 in CD and UC, 
as well as its safety and effectiveness in the context of contemporaneous SOC Remicade, the 
study plans to enrol approximately 2,500 patients in a mix of academic and community sites 
in approximately 13 countries where CT-P13 and Remicade are authorised for the treatment 
of CD and UC.  In order to meaningfully describe expected subgroups in this heterogeneous 
patient population under treatment, approximately 1,900 of the patients enrolled will be 
included in the CT-P13 cohort.  All patients are expected to be enrolled over an approximate 
30-month period.  Study participation of all ongoing patients will continue up to a 2-year 
follow-up period, or until the end of the last patient 1-year follow-up period, whichever 
occurs first.  Enrolled patients who permanently discontinue infliximab (CT-P13 or 
Remicade) treatment will be encouraged to remain in the study and be followed for the 
remainder of the study period using a simplified case report form (CRF). 
In compliance with the observational methodology of the study there will be no study visits
mandated per the study protocol.  Patients’ visit schedules will follow local SOC, typically 
coinciding with the schedule of infusions of CT-P13 or Remicade, with additional visits as 
needed at the treating physician’s discretion.  Data for the study will be entered into an 
electronic data capture (EDC) system at enrolment and then approximately every 3 months 
(at a minimum) thereafter up to a 2-year follow-up period, or until the end of the last patient 
1-year follow-up period, whichever occurs first.  When possible, in order to adequately 
manage EDC entry sites are encouraged to enter data in the EDC within 10 days of a 
patient’s visit data collection date.  Data collection requirements for safety events, which 
need to be reported to Pfizer within specified timelines, are detailed in Section 10.
Population
The target study population will include patients with CD or UC, who are being treated with,
or initiating treatment with, CT-P13 (or Remicade for the SOC cohort) at the time of study 
enrolment.  Below are the few examples of different treatment subgroups that can possibly be 
enrolled in the study:

Biologic-naïve patients initiating CT-P13 (or Remicade).

Patients currently being treated with CT-P13 (or Remicade).

Patients who are considered stable by the Investigator under Remicade therapy for 
CD or UC, who switch to CT-P13.

Patients switching to CT-P13 (or Remicade) from an alternative biologic therapy 
(eg, adalimumab) due to non-responsiveness to or intolerance.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 10 of 56

Patients re-initiating infliximab (CT-P13 or Remicade) after having successfully 
completed and exited a previous course of infliximab therapy in the past.
Patients with fistulating disease or stomas, and those receiving combination therapy will be 
included.
Variables
Primary variables: 

Patients’ demographic characteristics.

Clinical and diagnostic characteristics.

Relevant medical history of CD or UC including prior treatments.

CT-P13 treatment.

CT-P13 and Remicade switches and reasons for switch.

Dose and frequency, augmentation/reduction and reasons of changes.

Co-therapy(ies) related to the management of CD or UC.

All Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of 
Special Interest (AESIs), and events in a special situation (eg, pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation; lack of 
efficacy; and occupational exposure) during the patient study participation. 
Secondary variables: 

Clinical assessment of disease activity.

Data relating to the Harvey Bradshaw Index (HBI) for patients with CD.

Data relating to the Partial Mayo Scoring System for Assessment of UC Activity 
(the abbreviated version excluding the endoscopy sub-score).

Data relating to the Montreal classification index for CD.

Data relating to the Montreal classification index for UC: 

Classification by extent.

Classification by severity.

Data relating to the fistula drainage assessment index for CD.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 11 of 56

Laboratory results related to the treatment or assessment of CD or UC.

Imaging results related to the treatment or assessment of CD or UC.
 
 
Data Sources
CRFs will be designed to gather the data needed for the study that are collected as part of 
local SOC of the study patients.  Clinical information recorded in the patients’ medical 
record information will be abstracted and entered into the EDC system.  As well, patients 
will complete the paper-based PRO questionnaires.
Study Size
The study will enrol approximately 2,500 patients with CD or UC, who are either already 
being treated or initiating treatment with CT-P13 or Remicade.  The study is designed 
primarily to characterise the use of CT-P13 in patients with CD or UC. 
Data Analysis
Considering this study is not designed to test specific hypotheses, the statistical analysis will 
be descriptive in nature.  Given the expected heterogeneity of patients commonly seen in 
observational studies, patients will be stratified (eg, UC vs. CD, by subgroup, by country) 
based on final data available for analysis.  Data permitting, post hoc inferential analysis may 
be used to examine the impact of risk factors or predictors on outcomes of interest, as 
appropriate.  Detailed procedures of all analyses will be described in the Statistical Analysis 
Plan (SAP).
Milestones
Start of data collection
(First Subject First Visit (FSFV))
22 April 2015
End of data collection
(Last Subject Last Visit (LSLV))
Approximately 31 October 2018
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 12 of 56
Registration in the EU PAS register
TBD
Final Study Report
Approximately 06 February 2019

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 13 of 56
4. AMENDMENTS AND UPDATES
Amendment 
Number
Date
Substantial or 
Administrative 
Amendment
Protocol Section(s) Changed 
Summary of Amendment(s)
Reason
1
23 Feb 2015
Substantial
Hospira protocol format 
sections: 
1.
Throughout document.
2.
List of abbreviations, 
References.
3.
Throughout document 
pertaining to protocol title.
4-8. Abstract, Patient eligibility, 
Primary outcomes, 
Secondary outcomes, 
Exploratory outcomes, 
Study limitations, Study 
data Collection Schedule 
Table.
9. Secondary study objectives.
10. Figure 1.
11. Enrolment.
12. Inclusion criteria.
13. Inclusion criteria.
14. Adverse Events of Special 
Interest (AESI) Table 3.
15. Appendix 3.
16. Appendix 4.
17. Appendix 5.
18. Appendix 8.
19. Sponsor Signatures Page.
1.
IBD specified as Crohn’s disease (CD) or 
Ulcerative Colitis (UC).
2.
3.
Infliximab was added in brackets next to 
Inflectra.
4.
Abstract: the sentence ‘Patients with 
fistulating disease or stomas and those 
receiving combination therapy will be 
included’ was added to population 
section.
5.
‘In the six months prior to enrolment for 
biologic naïve patients or in the 12 
months prior to enrolment for biologic 
experienced patients’ wording was 
removed from study outcomes section.
6.
‘Data relating to the Montreal 
classification index for UC: classification 
by extent, classification by severity, Data 
relating to the fistula drainage 
assessment index for CD’ were added.
7.
 
 
8.
The wording ‘For all patients with 
“prevalent exposure,” data collection will 
include information on any AESI and 
SAE experienced during Inflectra or 
Remicade treatment prior to study 
enrolment, so that any AESI that occur 
shortly after treatment initiation will not 
be under-represented in the study 
population. A safety analysis will 
1.
Updated to clarify IBD indications.
2.
 
 
3.
Updated for consistency.
4.
Added to clarify that these patient types 
would be permitted for study enrolment.
5.
Under the Legacy Hospira process, this 
wording was removed because SAEs and 
AESI prior to enrolment would not be 
collected.
6.
Included as additional clinical assessments 
to the secondary outcomes section. 
7.
 
8.
Under the Legacy Hospira process, this 
wording was removed because SAEs and 
AESI prior to enrolment would not be 
collected.
9.
Added to clearly define effectiveness as 
opposed to efficacy.
10. Updated to reflect the definition of IBD as 
CD or UC.
11. Updated wording to correctly describe the 
study enrolment process.
12. Updated wording as the first course of 
treatment of the adolescence population in 
the UK is Remicade.
13. Added wording to indicate additional 
CCI
CCI
CCI
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 14 of 56
compare AESIs and SAEs experienced 
during Inflectra or Remicade treatment 
prior to enrolment with events after 
enrolment’ was removed from study 
limitations section
9.
The following sentence was added 
“Effectiveness is a measure of the extent 
to which a specific intervention, 
procedure, regimen, or service when 
deployed in the field in routine 
circumstances, does what it is intended to 
do for a specified population.  
‘Effectiveness’ should be distinguished 
from ‘efficacy’, which is a measure of 
the extent to which a specific 
intervention, procedure, regimen, or 
service produces a beneficial result under 
ideal conditions.”
10. The study design schematic was updated.
11. Enrolment process wording changed to 
‘Patients will be recruited for the study 
during the course of usual care at each 
investigative site.  Patients deemed 
potentially eligible for the study by their 
physician will be invited to participate.  
At the time of study invitation, 
consenting patients may be enrolled if 
they are eligible to be included in either 
the Inflectra or the Remicade cohort and 
meet study inclusion and exclusion 
criteria.
12. Inclusion criterion 1: ‘At least 18 years 
of age at the time of initial confirmed 
diagnosis of IBD’ was changed to ‘at 
least 12 years at the time of initial 
confirmed diagnosis of CD and UC and 
at least 18 years at the time of enrolment 
to the study.’
13. Inclusion criterion 2: The following 
sentence was added ‘Patients with 
patient subgroups included.
14. Wording removed as requested during 
National Leader meeting review of 
protocol.
15. Added to describe the ‘Montreal 
Classification’ of Crohn’s Disease clinical 
assessment.
16. Added to describe the ‘Montreal 
Classification’ of Ulcerative colitis clinical 
assessment.
17. Added to describe the ‘Fistula drainage 
assessment’ of Crohn’s Disease clinical 
assessment.
18. Added to include a detailed description of 
protocol updates.
19. Updated Sponsor contact information.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 15 of 56
stomas or surgery/pouch will also be 
included” to indicate additional patient 
subgroups included.’
14. ‘Infusion reaction associated with 
shortened infusion duration [RA [RA)’ 
was deleted.
15. Added the ‘Montreal Classification’ of 
Crohn’s Disease clinical assessment.
16. Added the ‘Montreal Classification’ of 
Ulcerative colitis clinical assessment.
17. Added the ‘Fistula drainage assessment’ 
of Crohn’s Disease clinical assessment.
18. Added descriptions of protocol updates.
19.
 is 
replacing 
.
2
25 Aug 2017 Substantial
All (change in template used)
1.
Changed from Hospira Protocol 
Template to Pfizer Non-Interventional
Study Protocol Template.
2.
Study classification of PASS applied. 
3.
Updated immunogenicity data collection 
so that sites that conduct immunogenicity 
analysis as part of their local clinical care 
practice will be able to offer patients the 
option to participate.  There is no longer 
a central lab option.
4.
Requirement for informed consent as 
Inclusion criteria added.
5.
Safety reporting requirement updated 
including Pfizer safety reporting details. 
6.
Changed number of countries 
participating in the study.
7.
Study population changed from 
3,300 total (2,500 Inflectra and 
800 Remicade) to 2,500 total 
1.
Updated to align with Pfizer’s processes.
2.
Voluntary PASS registration as per EU 
legislation.
3.
Updated so it is clear that only those sites 
who conduct immunogenicity analysis as 
part of their routine patient care have the 
option for patients to provide this data 
collection.
4.
Added to clarify requirement of informed 
consent for patient enrolment.
5.
Updated to align with Pfizer’s procedures. 
6.
Updated for correct final number of 
participating countries.
7.
Population modified to end study early. 
8.
Duration of patient participation adjusted 
from a 2 to 1 year follow-up period to end 
data collection early.
9.
Switched from trade name to molecular 
PPD
PPD

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 16 of 56
(1,900 CT-P13 and 600 Remicade).
8.
Wording added to indicate patient 
participation will complete after the last 
1-year of follow-up data collection. 
9.
Change to naming of drug from Inflectra 
to CT-P13.
10. Study objective wording updated with 
regard to CT-P13 designation and change 
in 2 year follow-up period.
11. Included wording that there may be an 
option to conduct one or more interim 
analyses.
12. Removed reference to Good Clinical 
Practice (GCP).
13. Updated author and MAH contact 
information.
14. Included text encouraging EDC data 
entry within 10 days of a patient visit 
date.
name to permit either Inflectra or Remsima 
use.
10. Updated for consistency with CT-P13 
designation and study duration.
11. Updated wording to allow for the option to 
conduct one or more interim analyses if 
deemed necessary.
12. Updated to applicable ethical conduct 
standards (eg, Good 
Pharmacoepidemiology Practices, Good 
Epidemiological Practices, etc.) since this is 
a non-interventional study.  Please 
reference Sections 8.8 and 9.4.
13. New contact information provided since the 
previous protocol Amendment 1.
14. Text added to recommend data entry work 
load.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 17 of 56
5. MILESTONES
Milestone
Planned date
Start of data collection (FSFV)
22 April 2015
End of data collection (LSLV)
31 October 2018
Registration in the EU PAS register
To be determined
Final study report
06 February 2019
6. RATIONALE AND BACKGROUND
Remicade (infliximab, Janssen Biotech, Inc.), an IgG1 chimeric human-murine monoclonal 
antibody (mAb), was authorised for approval in Europe in August 1999.  Since then, it has 
been utilised in many thousands of patients for the treatment of 2 major types of 
inflammatory bowel disease (IBD), Crohn’s Disease (CD) and ulcerative colitis (UC).  
Infliximab was designed to bind to tumour necrosis factor-(TNF-), and prevent it from 
binding to its endogenous receptors.  Since its original characterization, infliximab has been 
shown to act through a multitude of additional mechanisms of action beyond 
TNF-neutralization in inflammatory bowel disease.
In September 2013, CT-P13 (infliximab), a mAb biosimilar to reference Remicade, was 
approved by the European Medicines Agency (EMA) based on an extensive biosimilar 
comparability exercise, which demonstrated that quality, as well as the clinical efficacy, 
pharmacokinetics and safety profile of CT-P13 are highly similar to that of Remicade.  
CT-P13 is an IgG1 chimeric human-murine mAb biosimilar to Remicade produced in the 
same type of cell-line as Remicade.  In addition to extensive non-clinical comparability 
testing of molecular structure and function, including those mechanisms of action thought to 
be important in CD or UC, the approval of CT-P13 in Europe was also based on the results of 
2 large, double-blind, randomised clinical trials (RCTs): a phase I-type Programme 
evaluating the Autoimmune disease investigational drug CT-P13 in ankylosing spondylitis 
(PLANETAS) in 250 patients with ankylosing spondylitis, and a Phase III-type study 
Programme evaluating the Autoimmune disease investigational drug CT-P13 in rheumatoid 
arthritis (PLANETRA) in 606 patients with rheumatoid arthritis.  These 2 studies
demonstrated that the pharmacokinetics and clinical efficacy of CT-P13 were equivalent 
based on pre-specified criteria to that of Remicade, and that the two treatments were well 
tolerated with comparable immunogenicity and safety profiles.  Based on the totality of 
evidence submitted demonstrating that CT-P13 was highly similar to Remicade, the 
European Medicines Agency (EMA) granted licensure for CT-P13 equivalent to the license 
for Remicade.  This marketing authorisation of CT-P13 included all approved indications for 
Remicade including the extrapolated indications of moderate to severe CD and UC. 
A summary of key findings presented in the CT-P13 European Public Assessment Report of 
the non-clinical evidence supporting extrapolation to the CD or UC indications are listed 
below: 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 18 of 56

Comparable binding to soluble transmembrane bound TNF-compared to Remicade.

Comparable binding to FcRIa, FcRIIa, FcRIIb and FcRn, C1q compared to 
Remicade.

Reduced binding (~20% by SPR vs. Remicade) to rFcRIIIa and rFcRIIIb in vitro.

Difference in the level of afucosylated glycans, Man5 and G0 for CT-P13: 
total 5.46 - 6.26% vs. Man5, G0 and G2 for Remicade: total 11.91 - 14.61%.

Ex vivo testing in representative physiological environments, demonstrated that
differences in binding to FcRIIIa and in ADCC activity, were abolished in the 
presence of:

serum of a CD patient;

peripheral blood mononuclear cells preparations (vs. isolated NK cells);

whole blood.

The EMA’s interpretation was that the difference in binding affinity was overcome by 
competition from plasma IgGs, soluble factors, immune complexes and presence of 
mixed cell populations expressing multiple FcRs.  At inflammatory sites, the vascular 
permeability is increased, which allows for many blood components to enter the extra 
vascular space.  “A range of arguments and experiments enable to conclude with a 
high level of probability that the quality differences detected in the level of 
afucosylation and binding to FcRIIIa are not clinically relevant.”

“In conclusion, by using a range of experimental models that are considered 
representative of the pathophysiological conditions and putative mechanisms of 
action of infliximab, the Applicant has provided convincing evidence that the 
difference detected in the amount of afucosylated species has no clinically relevant 
impact on the efficacy and safety of CT-P13, in particular in IBD.  Additional in vitro 
data from human intestinal cells are further supporting extrapolation of the clinical 
data to IBD.”
This study is designed to capture data from real-world clinical practice to characterise the 
population and document drug utilisation patterns.  In addition, available safety data will be 
collected and effectiveness of CT-P13 in the context of standard of care (SOC) utilisation of 
Remicade, in patients with CD or UC and to document the safety and effectiveness of 
CT-P13.
This non-interventional study is designated as a Post-Authorisation Safety Study (PASS) and 
is conducted voluntarily by Pfizer.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 19 of 56
7. RESEARCH QUESTION AND OBJECTIVES
7.1. Primary Study Objective

To characterise the population and drug utilisation patterns of patients treated with 
CT-P13 for CD or UC in the context of SOC Remicade.

To explore the long-term safety profile of CT-P13 in the treatment of patients with 
CD or UC in the context of SOC Remicade.
7.2. Secondary Study Objective

To assess the effectiveness1 of CT-P13 in the treatment of patients with CD or UC in 
the context of SOC Remicade.  Effectiveness is a measure of the extent to which a 
specific intervention, procedure, regimen, or service when deployed in the field in 
routine circumstances, does what it is intended to do for a specified population.  
‘Effectiveness’ should be distinguished from ‘efficacy’, which is a measure of the 
extent to which a specific intervention, procedure, regimen, or service produces a 
beneficial result under ideal conditions.
 
8. RESEARCH METHODS 
8.1. Study Design
This study is a multi-national, multi-centre, observational cohort study of patients with CD or 
UC, who are treated with CT-P13 (or Remicade for the smaller SOC cohort).  The decision to 
treat with CT-P13 or Remicade will be made at the usual care discretion of the physician 
independent of and before the decision to enrol patients in the study.  In order to characterise 
the population and drug utilisation patterns associated with the use of CT-P13 in CD and UC, 
as well as its safety and effectiveness in the context of contemporaneous SOC Remicade, the 
study plans to enrol approximately 2,500 patients in a mix of academic and community sites 
in approximately 13 countries where CT-P13 and Remicade are authorised for the treatment 
of CD or UC.  In order to meaningfully describe expected subgroups in this heterogeneous 
patient population under treatment, approximately 1,900 of the patients enrolled will be 
included in the CT-P13 cohort.  All patients are expected to be enrolled over an approximate 
30-month period. Study participation of all ongoing patients will continue up to a 2-year 
follow-up period, or until the end of the last patient 1-year follow-up period, whichever 
occurs first.  Enrolled patients who permanently discontinue infliximab (CT-P13 or 
Remicade) treatment will be encouraged to remain in the study and be followed for the 
remainder of the study period using a simplified CRF.
In compliance with the observational methodology of the study, there is no study visit 
mandated per study protocol.  Patients’ visit schedules will follow local SOC, typically 
coinciding with the schedule of infusions of infliximab, with any additional visits at the 
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 20 of 56
treating physician’s discretion.  Additionally, for sites that conduct immunogenicity analysis 
as part of their routine clinical care, there will be an option for enrolled CT-P13 patients to 
provide immunogenicity profile information as part of the data collection for the study.  The 
immunogenicity data will only be described; there will be no attempt to draw an inference on 
similarity.  Please reference Appendix 9 (Optional Immunogenicity Data Collection) for 
more information.  Medical information will be recorded in patients’ medical records during 
every clinic visit.  Data for the study will be extracted from medical record information and 
entered into the EDC system at enrolment and then approximately every 3 months (at a 
minimum) thereafter, up to a 2-year follow-up period, or until the end of the last patient 
1-year follow-up period, whichever occurs first.  When possible, in order to adequately 
manage EDC entry sites are encouraged to enter data in the EDC within 10 days of a 
patient’s visit data collection.  The study design is presented schematically in Figure 1.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 21 of 56
Figure 1.
Study Design Schematic
Error!
RESULTS
PRE-
ENROLMENT
Data 
Entry into
the EDC**
(approximately
Every 3 months)
ENROLMENT
PATIENT ENROLMENT
Diagnosis of 
Crohn’s Disease (CD)
Diagnosis of 
Ulcerative Colitis (UC) 
Data Analysis‡
Reporting and Dissemination
Enrolment
• Eligibility assessment
• Clinical & Diagnostics
• Infliximab treatment
• Co-therapy for CD or UC 
• Clinical assessment
• Laboratory/imaging results
• AEs, SAEs, AESIs and
special situation events*** 
•
Obtain written informed consent from eligible 
patients
Physician decision to treat with
infliximab (CT-P13 or Remicade)
**Updates of clinical information are recorded in 
patient’s records during each treatment/clinical visit; 
however, data entry into the EDC occurs approximately 
every 3 months (at a minimum), 
. In order to adequately manage
EDC entry, sites are encouraged to enter data in the EDC
within 10 days of a patient’s visit data collection date.
†PaƟent switching between CT-P13 and Remicade will 
be followed until end of study with the full CRF.  Those 
who discontinue infliximab treatment, will be followed 
up with a simplified CRF for the remainder of the study 
period.  Refer to Table 1 for details.
‡Data collected on paƟents with CD and UC may be 
analysed separately.
Quarterly Follow -up†
• Infliximab treatment
• Co-therapy for CD or UC 
• Clinical assessment
• Laboratory/ Imaging 
results
• NS-AEs, SAEs , AESIs and
special situation events***
•
*** Special situation events are detailed in Section 10.
     Along with SAEs and AESIs, they must be reported         
     within 24 hours of site awareness.
C
CI
C
C
I
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 22 of 56
8.2. Setting
8.2.1. Inclusion Criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study:
1. At least 12 years of age at the time of initial confirmed diagnosis of CD or UC and at 
least 18 years of age at the time of enrolment to the study.
2. Patients who are prescribed CT-P13 or Remicade for the treatment of CD or UC 
according to the corresponding summary of product characteristics (SmPC) as 
determined by the Investigator.  Patients with stomas or surgery/pouch will be 
included.
3. Evidence of a personally signed and dated informed consent document indicating that 
the patient (or a legally acceptable representative) has been informed of all pertinent 
aspects of the study. 
8.2.2. Exclusion Criteria
Patients meeting any of the following criteria will not be included in the study:
1. Any reported contraindications for CT-P13 or Remicade, according to the 
SmPC/Product Label.
2. Known hypersensitivity (including severe, acute infusion reactions) to infliximab, its 
excipients or other murine proteins, at the time of enrolment.
3. Prior history of failure to respond to Remicade or CT-P13.
8.2.3. Regions/Number of Study Sites
The study will take place in countries in which CT-P13 and Remicade are authorised for the 
treatment of CD and UC.  A heterogeneous sample of about 150 sites is planned to be 
recruited in approximately 13 countries.  This will include a mix of academic and community 
centres to ensure broad physician and patient representation.  As this study is designed 
primarily to characterise the use of CT-P13, sites prescribing only Remicade to treat CD or 
UC (ie, not prescribing CT-P13 for CD or UC) will not be recruited in the study.
8.2.4. Enrolment
In order to meaningfully describe expected subgroups in this heterogeneous patient 
population under treatment, approximately 1,900 of the patients enrolled will be included in 
the CT-P13 cohort.  In order to assure this number of CT-P13 patients is enrolled, enrolment 
will be closely monitored in real time through the EDC system.  It is expected that depending 
on local formulary regulations or institutional policies, there may be sites that prescribe either 
Remicade or CT-P13 but not both.  Sites that only utilise Remicade will not be recruited to 
participate in the study. 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 23 of 56
Patients will be recruited for the study during the course of usual care at each investigative 
site.  Patients deemed potentially eligible for the study by their physician will be invited to 
participate.  At the time of study invitation, consenting patients may be enrolled if they are 
eligible to be included in either the CT-P13 or the Remicade cohort and meet study inclusion 
and exclusion criteria (Sections 8.2.1 and 8.2.2).
8.2.5. Patient Eligibility
The target study population will include patients with CD or UC, who are being treated, or 
initiating treatment, with CT-P13 (or Remicade for the SOC cohort) at the time of study 
enrolment. 
Below are the few examples of different treatment subgroups that can possibly be enrolled in 
the study:

Biologic-naïve patients initiating CT-P13 (or Remicade);

Patients currently being treated with CT-P13 (or Remicade);

Patients who are considered stable by the Investigator under Remicade therapy for 
CD or UC, who switch to CT-P13;

Patients switching to CT-P13 or Remicade from an alternative biologic therapy 
(eg, adalimumab) due to non-responsiveness to or intolerance;

Patients re-initiating CT-P13 or Remicade after having successfully completed and 
exited a previous course of infliximab therapy in the past.
Patients with fistulating disease or stomas and those receiving combination therapy will be 
included.
8.3. Variables
8.3.1. Primary Outcomes Variables

Patients’ demographic characteristics.

Clinical and diagnostic characteristics.

Relevant medical history for CD or UC including prior treatments.

CT-P13 treatment.

CT-P13 or Remicade switches and reasons for switch.

Dose and frequency, augmentation/reduction and reasons for changes.

Co-therapy(ies) for the management of CD or UC.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 24 of 56

All adverse Events (AEs), Serious Adverse Events (SAEs) or Adverse Events of 
Special Interest (AESI), and events in a special situation (eg, pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation; lack of 
efficacy; and occupational exposure) during patient study participation.
8.3.2. Secondary Outcomes Variables

Clinical assessment of disease activity.

Data relating to Harvey Bradshaw Index (HBI) for patients with CD.

Data relating to Partial Mayo Scoring System for Assessment of UC Activity, 
ie, abbreviated version without the endoscopy sub-score.6

Data relating to the Montreal classification index for CD.

Data relating to the Montreal classification index for UC: 

Classification by extent.

Classification by severity.

Data relating to the fistula drainage assessment index for CD.

Laboratory results related to the treatment or assessment of CD or UC.

Imaging results related to the treatment or assessment of CD or UC.
 
 
8.4. Data Sources
CRFs will be designed to gather the data needed for the study that are collected as part of 
SOC.  Patients will be completing a set of 
 instruments on paper during their SOC visits 
at enrolment and then approximately every 3 months (based on the visit that is closest in time 
to 3 months after the last visit) thereafter.  When possible, in order to adequately manage 
EDC entry, sites are encouraged to enter data in the EDC within 10 days of a patient’s visit 
data collection date.  Site research staff will enter 
 and patient-reported 
 data into 
the EDC system.  Patients’ medical record information, any relevant diagnostic reports, and 
CCI
CCI
CCI
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 25 of 56
the paper-based 
and patient-reported 
 survey are the source documents for study 
data collection.  Clinical information recorded in patients’ medical record information and/or 
diagnostic reports will be abstracted and entered into the EDC system, as well as the 
completed 
and patient-reported 
 survey.  Table 1 summarises the data collection 
schedule of the study.
CCI
CCI
CCI
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 26 of 56
Table 1.
Study Data Collection Schedule
Once at enrolment
Every 3 months up to a 2-year follow-up 
period, or until the end of the last patient 
1-year follow-up period, whichever occurs 
first
Enrolment
Follow-up Period*
Infliximab Treatment 
Discontinuation**
Eligibility assessment and written informed consent 
X
Relevant medical history for CD or UC 

Diagnosis of CD or UC: extent, severity, duration

Prior treatments
X
Infliximab therapy – CT-P13 or Remicade 

Dose, frequency: augmentation/reduction, reasons of 
changes

Switch(es) or discontinuation, reasons of 
switch/discontinuation
X
X
Co-therapy (frequency, dose, augmentation/reduction, 
switching, reason of switch)

Steroid use

Medication(s) relating to the treatment of CD or UC 
or management of the symptoms of CD or UC

Medication(s) relating to the management of 
SAE/AESI
X
X
X
Clinical assessment

Data relating to Harvey-Bradshaw Index (HBI) for 
CD

Data relating to Partial Mayo Scoring System for 
Assessment of Ulcerative Colitis Activity for UC 
(abbreviated version excluding endoscopy sub-score) 

Montreal classification for CD

Montreal classification for UC: 

Classification by extent

Classification by severity

Fistula drainage assessment

Clinical remission/relapse
X
X
X**
Laboratory results leading to CD or UC treatment 
decision***
X
X

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 27 of 56
Imaging results leading to CD or UC treatment decision
X
X
 
X
X
Safety outcomes

Serious adverse event (SAE)

Adverse Events of Special Interest (AESI)

Non-serious AEs

Special Situations 
Within 24 hours
of awareness for 
SAE, AESI and 
special situations.  
Non-serious AEs 
will follow 
standard data 
collection 
timelines
Within 24 hours
of awareness for 
SAE, AESI and 
special situations.  
Non-serious AEs 
will follow 
standard data 
collection timelines
Within 24 hours of 
awareness for SAE, 
AESI and special 
situations.  Non-serious 
AEs will follow 
standard data collection 
timelines
*
Recording of medical data into patients’ medical record information occurs during their usual care visit.  Data entry into the 
EDC system occurs approximately every 3 months at a minimum.  However, sites are encouraged to enter all standard of care 
visits completed within each three month period into the EDC, and when possible conduct entry within 10 days of each patient’s 
data collection visit date.
**
Patients who discontinue infliximab treatment will be encouraged to remain in the study and be followed for the remainder of the 
study period using a simplified CRF.  HBI, Partial Mayo scoring, Montreal classification for CD or UC and fistula drainage 
assessment may not be applicable to simplified data capture depending on local SOC, but information on clinical remission or 
relapse will be captured to the extent possible.  Clinical assessment forms are within the treatment discontinuation visit CRF.
*** For sites that conduct local practice of immunogenicity analysis, patients will have an option to provide immunogenicity results 
for data collection.  The data collected should include the most recent test results just prior to enrolment, and for any tests 
performed during patient study participation.  Please reference Appendix 9 (Optional Immunogenicity Data Collection) for more 
information.
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 28 of 56
8.5. Study Size
The study will enrol approximately 2,500 patients with CD or UC, who are either already 
being treated or initiating treatment with CT-P13 or Remicade.  The study is designed 
primarily to characterise the use of CT-P13 in patients with CD or UC.  Patients being 
initiated or treated with Remicade will constitute a smaller although substantial SOC cohort 
and are expected to provide context for the CT-P13 cohort.  The sample size is based on both 
practical and statistical considerations.  The sample size must be relatively large given there 
are 2 diseases (CD and UC) under study with 5 population subgroups within each.  
Additionally, the study will seek to characterise population and drug utilisation patterns 
across 13 countries.  In order to meaningfully describe expected subgroups in this 
heterogeneous patient population under treatment, approximately 1,900 of the patients 
enrolled will be included in the CT-P13 cohort.  There is no calculation of power for this 
study because the objectives are descriptive rather than inferential.
In achieving one part of the primary objective of the study of documenting the safety of 
CT-P13 in real-world clinical practice, the simulated rates of all NS-AEs, SAEs and AESIs
associated with the use of infliximab are being used to estimate the sample size of the study.  
The table below shows the 2-sided confidence intervals associated with observed AESI rates 
ranging from 0.1% to 10% in patient populations of 625 and 1875 patients.  The confidence 
intervals are exact binomial 95% confidence intervals. 
Table 2.
Observed AESI Rates
Precision of Observed AESI Rates with a Sample Size of 625
(2-sided 95% confidence interval)
Observed Rate
Exact 95% Confidence Interval
0.1%
0.00, 0.59
0.5%
0.10, 1.40
1.0%
0.35, 2.08
2.0%
1.00, 3.33
5.0%
3.39, 6.97
10.0%
7.69, 12.54

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 29 of 56
Precision of Observed AESI Rates with a Sample Size of 1875
(2-sided 95% Confidence Interval)
Observed Rate
Exact 95% Confidence Interval
0.1%
0.00, 0.30
0.5%
0.22, 0.91
1.0%
0.57, 1.51
2.0%
1.39, 2.71
5.0%
4.02, 6.04
10.0%
8.65, 11.42
8.6. Data Management 
8.6.1. Electronic Data Capture (EDC) System
The database will be designed using DataTrak One, a proprietary electronic data capture 
(EDC) system provided by DataTrak International, Inc., a third party vendor contracted by 
Hospira, a Pfizer company in accordance with written security policies.
8.6.2. Data Entry
All reported data from the enrolled Investigator’s site will be entered via a secure web-based 
EDC study database.  All sites will be fully trained in using the EDC system, including CRF 
completion guidelines.  Site personnel will be provided with secure usernames and 
passwords in order to enter study data into the EDC system.  All participating sites will only 
have access to view and enter the data for their own patients.  A data manager will perform 
concurrent review during the course of the data collection period.  The data manager will 
generate ad-hoc queries to sites when required, and the site management team will follow-up 
to request completion of such queries.
8.6.3. Statistical Software
All analyses will be performed using SAS for Microsoft Windows operating system
statistical software (SAS Institute, Cary, North Carolina, USA) version 9.2 or higher, using 
validated implementations of each application or SAS custom programming.
8.7. Data Analysis 
Considering the observational design of the study is not designed to test specific hypotheses, 
the statistical analysis will be descriptive in nature.  Summary tabulations will be presented 
that will display the number of observations (N), mean, standard deviation (SD), median, 
minimum and maximum for continuous variables.  For categorical variables, N and percent 
will be provided.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 30 of 56
In keeping with one component of the primary objective of evaluating the long-term safety 
profile of CT-P13, for each type of SAE and AESI, both incidence rate and 
exposure-adjusted incidence rate will be calculated with confidence intervals.  Generalised 
linear models will be used to examine the impact of risk factors and predictors on outcomes 
of interest, as appropriate.
As this is an observational study, not designed to test any a priori hypotheses, the sample 
size selected may not be sufficient to detect any statistical significance.  Given the expected 
heterogeneity of patients commonly seen in observational studies, patients will be stratified 
(eg, UC vs. CD, by subgroup, by country) based on final data available for analysis.  Data 
permitting, post hoc inferential analysis may be used to examine the impact of risk factors or 
predictors on outcomes of interest, as appropriate. 
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a Statistical Analysis Plan (SAP), which will be dated, filed and 
maintained by the sponsor.  The SAP may modify the plans outlined in the protocol; any 
major modifications of primary endpoint definitions or their analyses would be reflected in a 
protocol amendment.
There is an option to conduct one or more interim analyses during the course of the study.
8.8. Quality Control
Quality Assurance representative(s) of Hospira, a Pfizer Company (or their designee) may 
conduct audit visits at any time during the study period.  All necessary related data and 
documents will be made available for inspection.
8.8.1. Site Training and Initiation
Meetings will be held to train the Investigators (treating physicians) and their site staff on the 
study requirements and use of the EDC system.  Pfizer (or their designee) will contact each 
site to review site initiation procedures.  Ongoing site management will occur throughout the 
entire duration of the study.  Additional outreach and training including on-site visits will 
occur for sites (Investigators and staff) needing remedial training and to address quality 
control concerns prior to analysis.
8.8.2. Site Monitoring
In-house site management or remote monitoring will be used to manage sites during the 
operational/maintenance phase of the programme.  Site contact will be more frequent during 
enrolment and then decrease during the subject follow-up period due to more limited site 
involvement.  All inbound calls from sites will be triaged immediately and all calls (inbound 
and outbound) will be tracked, including inquiry type, site identification (ID), query 
resolution and centre feedback.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 31 of 56
8.9. Strengths and Limitations of the Research Methods
8.9.1. Lost to Follow-up
All patients will be followed for up to a 2-year follow-up period, or until the end of the last 
patient 1-year follow-up period, whichever occurs first.  If a patient misses more than 1 usual 
care visit, the site will attempt to communicate with the patient and document the patient’s 
reason for not returning.  Sites should follow their normal follow-up procedures to attempt 
patient contacts, whether at various times of the day and evening, and on different days of the 
week.  If the patient cannot be contacted after the due diligence process, the treating 
physician should consider other methods, such as an attempt to contact the patient’s 
designated secondary contacts (including the patient’s general practitioner and next of kin or 
out-of-household contacts) to obtain information on the patient’s whereabouts and vital 
status.  If the patient’s care has been transferred to another healthcare professional (HCP), the 
treating physician at the enrolling site will be responsible for obtaining the required 
follow-up information from the new treating physician.  Patients who do not return for at 
least 2 scheduled visits, and for whom no information is available will be considered lost to 
follow-up.
8.9.2. Study Limitations
Recognising that this is a non-interventional observational study, there are some limitations 
or potential biases inherent in this study design: survivor bias, selection bias and the risk of 
systematic longer follow-up period in the Remicade patient group (given the higher 
probability of current use).  The observational study will include patients who initiated 
CT-P13 or Remicade prior to implementation of the study (“prevalent exposure”).  One 
limitation of this approach is that patients who initiate treatment and discontinue shortly 
thereafter would not be included and could differ in demographic and clinical characteristics 
from those who become enrolled (“survivor bias”).  A further limitation of this approach is 
that Remicade patients are more likely to be prevalent patients, while a higher proportion of 
CT-P13 patients will be biologic-naïve at the time of study entry.  This may have 
implications on 
 as biologic-naïve patients may present with less advanced disease.
Given the historic availability of Remicade safety and effectiveness information, the 
observation groups of the study will include different numbers of patients.  Therefore, the 
estimation of the true incidence of AEs will be supported by different statistical powers, 
according to those subgroup sizes.  The width of the confidence intervals around the 
estimated incidence rates will differ between subgroups (wider with Remicade).  
Consequently, the findings may be difficult to compare or the comparison may not be 
clinically meaningful.  Events may occur in the CT-P13 observation group, but the 
comparison groups may be too small to determine if the differences across the subgroups are 
significant.  Historically available information for Remicade may be utilised to provide 
additional context.  However, the findings from this study will be descriptive and not 
inferential in nature, due to the study nature and design.
CCI

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 32 of 56
8.10. Other aspects
8.10.1. National Leaders Committee
A National Leaders Committee (see Section 2) has been established which includes clinicians 
and scientists with expertise in CD or UC, epidemiology and biostatistics, with a National 
Leader chosen for each country involved in the study.  Committee members will provide 
ongoing subject matter expertise for the programme.  In collaboration with Hospira, a Pfizer 
Company, the Committee will be responsible to review the data from the study over time, to 
make recommendations to Pfizer regarding study conduct, and assist in study execution at the 
national and international levels.  The Committee will be involved in case report form review 
and development, statistical analysis plan development and review, Study Report review, as 
well as publication development, if the findings from the study warrant publications in the 
future. 
8.10.2. Concomitant Medication Use
As this is an observational study, where treatment decisions are left to the discretion of the 
treating physician, prescription of CT-P13 or Remicade or any other concomitant medication 
will not be influenced by the study protocol in any way.  Therefore, the current study 
protocol does not impose any restriction on the prescription of concomitant medications.  It is 
left to treating physician’s discretion taking into account local standard of care and SmPC 
directions.  With regard to co-therapy (ies), as indicated in Table 1, data on the following 
drug usage will be extracted from medical record information and entered into the EDC 
system:

Steroids.

Medication(s) related to the treatment of CD or UC or management of the symptoms 
of CD or UC.

Medication(s) related to the management of SAE or AESI.
Information on other types of concomitant medication will be recorded in the patients’ 
medical record information as per routine practice but will not be captured as part of study 
data.
8.10.3. Regulatory Authorities 
The approved protocol will be submitted to Regulatory Authorities in accordance with the 
regulations of the countries and participating sites’ local clinical research regulatory 
requirements when applicable.
8.10.4. Protocol Modifications
Amendments to the protocol can only be made by Pfizer.  All protocol amendments must be 
signed and dated by the Investigator physicians, and if required, submitted and approved by 
the Regulatory Authorities and Institutional Review Board/Independent Ethics Committees 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 33 of 56
(IRB/IEC), prior to implementation of the amendment.  The National Leaders Committee 
may provide feedback to Pfizer on protocol modifications.
8.10.5. Compensation to Investigators
Study Investigators will be compensated for time spent in completing study requirements 
consistent with local prevailing conditions.  This compensation schedule will be determined 
in accordance with national and local IRB/IEC guidelines and fair market value for the work 
performed.
9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws.  In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of patient personal data.
The informed consent form must be in compliance with local regulatory requirements and 
legal requirements.
The informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and Pfizer before use.
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The investigator, or a person designated by the 
investigator, will obtain written informed consent from each patient or the patient’s legally 
acceptable representative before any study-specific activity is performed.  The investigator 
will retain the original of each patient's signed consent form.
9.2. Patient Withdrawal
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons.  In any circumstance, every effort should be made to document 
subject outcome, if possible.  The investigator should inquire about the reason for withdrawal 
and follow-up with the subject regarding any unresolved adverse events. 
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 34 of 56
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and informed consent forms, and other relevant documents, 
(eg, recruitment advertisements), if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer. 
9.4. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE), Good Epidemiological Practice 
(GEP) guidelines issued by the International Epidemiological Association (IEA), Good 
Practices for Outcomes Research issued by the International Society for Pharmacoeconomics 
and Outcomes Research (ISPOR), International Ethical Guidelines for Epidemiological 
Research issued by the Council for International Organizations of Medical Sciences 
(CIOMS), European Medicines Agency (EMA) European Network of Centres for 
Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on Methodological 
Standards in Pharmacoepidemiology, and FDA Guidance for Industry: Good 
Pharmacovigilance and Pharmacoepidemiologic Assessment, Guidance for Industry: 
Patient-Reported Outcome Measures: Use in Medical Product Development to Support 
Labeling Claims and/or equivalent.
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
The table below summarizes the requirements for recording safety events on the case report 
form (CRF) and for reporting safety events on the Non-interventional Study (NIS) Adverse 
Event Report Form to Pfizer Safety.  These requirements are delineated for three types of 
events: (1) Serious Adverse Events (SAEs); (2) Non-serious AEs; (3) Adverse Events of 
Special Interest (AESIs); and (4) Special Situations - scenarios involving drug exposure, 
including exposure during pregnancy, exposure during breast feeding, medication error, 
overdose, misuse, extravasation, lack of efficacy and occupational exposure.  These events 
are defined in the section “Definitions of safety events”. 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 35 of 56
Safety event
Recorded on the 
CRF
Reported on the NIS AEM 
Report Form to Pfizer 
Safety within 24 hours of 
Awareness
SAE
All
All
Non-serious AE
All
Adverse Events of Special 
Interest (AESIs).
Please reference the list of 
AEs classified as AESIs for 
this study at the end of 
Section 10
Scenarios involving exposure to a 
drug under study, including 
exposure during pregnancy, 
exposure during breast feeding, 
medication error, overdose, misuse, 
extravasation, lack of efficacy, and 
occupational exposure
All (regardless of 
whether associated 
with an AE), 
except 
occupational 
exposure
All (regardless of whether 
associated with an AE)
For each AE, the investigator must pursue and obtain information adequate both to determine 
the outcome of the adverse event and to assess whether it meets the criteria for classification 
as a SAE (see section "Serious Adverse Events” below).
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to a drug under study.  In particular, if the SAE is fatal or 
life-threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information.  This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports.  In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events.
For safety events that are considered serious or that are identified in the far right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe.  In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the case report form.  In general, this will include a description of the 
adverse event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality.  Any information relevant to the event, such 
as concomitant medications and illnesses must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 36 of 56
Reporting Period 
For each patient, the safety event reporting period begins at the time of the patient’s first dose 
of CT-P13 or the time of the patient’s informed consent if s/he is already exposed to CT-P13, 
and lasts through the end of the observation period of the study, which must include at least 
28 calendar days following the last administration of a drug under study; a report must be 
submitted to Pfizer Safety (or its designated representative) for any of the types of safety 
events listed in the table above occurring during this period. If a patient was administered a 
drug under study on the last day of the observation period, then the reporting period should 
be extended for 28 calendar days following the end of observation.  Most often, the date of 
informed consent is the same as the date of enrollment.  In some situations, there may be a 
lag between the dates of informed consent and enrollment.  In these instances, if a patient 
provides informed consent but is never enrolled in the study (eg, patient changes his/her 
mind about participation), the reporting period ends on the date of the decision to not enroll 
the patient. 
If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to CT-P13, the SAE also must be reported 
to Pfizer Safety. 
Causality Assessment
The investigator is required to assess and record the causal relationship.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of 
each adverse event.  For AEs with a causal relationship to CT-P13, follow-up by the 
investigator is required until the event and/or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment. 
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that CT-P13caused or contributed to an adverse event.  If the 
investigator’s final determination of causality is “unknown” and s/he cannot determine 
whether CT-P13caused the event, the safety event must be reported within 24 hours. 
If the investigator cannot determine the etiology of the event but s/he determines that 
CT-P13did not cause the event, this should be clearly documented on the case report form 
(CRF) and the NIS AEM Report Form. 
DEFINITIONS OF SAFETY EVENTS
Adverse Events
An AE is any untoward medical occurrence in a patient administered a medicinal product.  
The event need not necessarily have a causal relationship with the product treatment or 
usage.  Examples of adverse events include but are not limited to:  

Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an adverse event);

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 37 of 56

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease; 

Lack of efficacy; 

Drug abuse; 

Drug dependency.
Additionally, for medicinal products, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Off-label use; 

Drug interactions;

Extravasation;

Exposure during pregnancy;

Exposure during breast feeding;

Medication error;

Occupational exposure.
Abnormal test findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 38 of 56

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or

Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
Serious Adverse Events
A serious adverse event is any untoward medical occurrence in a patient administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that:

Results in death;

Is life-threatening;

Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events);

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are considered
synonymous.  These cases are considered unexpected and handled as serious expedited cases 
by PV personnel.  Such cases are also considered for reporting as product defects, if 
appropriate.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 39 of 56
Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical 
importance.  Hospitalization in the absence of a medical AE is not in itself an AE and is not 
reportable.  For example, the following reports of hospitalization without a medical AE are 
not to be reported. 

Social admission (eg, patient has no place to sleep).

Administrative admission (eg, for yearly exam).

Optional admission not associated with a precipitating medical AE (eg, for elective 
cosmetic surgery).

Hospitalization for observation without a medical AE.

Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition (eg, for 
work-up of persistent pre-treatment lab abnormality).

Protocol-specified admission during clinical study (eg, for a procedure required by 
the study protocol).
Scenarios necessitating reporting to Pfizer Safety within 24 hours 
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.
Exposure during pregnancy
An exposure during pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed to (eg, environmental) CT-P13, or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to CT-P13(maternal exposure).
An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has been 
exposed to chemotherapeutic products).

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 40 of 56
2. A male has been exposed, either due to treatment or environmental exposure to 
CT-P13prior to or around the time of conception and/or is exposed during the
partner pregnancy (paternal exposure).
As a general rule, prospective and retrospective exposures during pregnancy reports from any 
source are reportable irrespective of the presence of an associated AE and the procedures for 
SAE reporting should be followed.
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with CT-P13, this information must be submitted
to Pfizer, irrespective of whether an adverse event has occurred using the NIS AEM Report 
Form and the EDP Supplemental Form. 
In addition, the information regarding environmental exposure to CT-P13in a pregnant 
woman (eg, a subject reports that she is pregnant and has been exposed to a cytotoxic product 
by inhalation or spillage) must be submitted using the NIS AEM Report Form and the EDP 
supplemental form.  This must be done irrespective of whether an AE has occurred. 
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy; in addition, 
follow-up is conducted to obtain information on EDP outcome for all EDP reports with 
pregnancy outcome unknown.  A pregnancy is followed until completion or until pregnancy 
termination (eg, induced abortion) and Pfizer is notified of the outcome.  This information is 
provided as a follow up to the initial EDP report.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (eg, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to investigational product.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 41 of 56
Additional information regarding the exposure during pregnancy may be requested.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). 
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner. It must be documented that the 
study participant was given this letter to provide to his partner.
Exposure during breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE.  An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding.
Medication error
A medication error is any unintentional error in the prescribing, dispensing or administration 
of a medicinal product that may cause or lead to inappropriate medication use or patient harm 
while in the control of the health care professional, patient, or consumer.  Such events may 
be related to professional practice, health care products, procedures, and systems including: 
prescribing; order communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; monitoring; and use. 
Medication errors include:

Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or 
prescription on the part of the healthcare provider or the patient/consumer).

Confusion with regard to invented name (eg, trade name, brand name).
The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE:

Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE.

Medication errors that do not involve a patient directly (eg, potential medication 
errors or near misses).  When a medication error does not involve patient exposure to 
the product the following minimum criteria constitute a medication error report:

An identifiable reporter;

A suspect product;

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 42 of 56

The event medication error.
Overdose, Misuse, Extravasation
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.
Lack of Efficacy
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product.
Occupational Exposure
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the 
investigator, irrespective of the presence of an associated AE/SAE.
Adverse Events of Special Interest
Adverse Events of Special Interest (AESIs) are AEs of scientific or medical concern specific 
to the product for which ongoing monitoring and rapid communication by the investigator to 
the sponsor can be appropriate.  The following list of AEs are classified as AESIs for this 
study:

Serious infections including sepsis (excluding opportunistic infections and 
tuberculosis);

Opportunistic infections;

Tuberculosis;

BCG breakthrough infection and agranulocytosis in infants with in utero exposure to 
infliximab;

Acute hypersensitivity reactions (including anaphylactic shock)*;

Serious infusion reactions during a re-induction regimen following disease flare;

Serum sickness (delayed hypersensitivity reactions);

Haematological reactions;

Systemic lupus erythematosus/lupus-like syndrome;

Lymphoma (not HSTCL);

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 43 of 56

Hepatosplenic T-cell lymphoma (HSTCL);

Leukaemia;

Merkel cell carcinoma;

Melanoma;

Cervical cancer;

Paediatric malignancy;

Hepatobiliary events;

HBV reactivation;

Congestive heart failure;

Demyelinating disorders;

Sarcoidosis/sarcoid-like reactions;

Intestinal or perianal abscess (in Crohn’s disease);

Malignancy (excluding lymphoma, HSTCL, paediatric malignancy, leukaemia, 
melanoma, Merkel cell carcinoma, cervical cancer);

Colon carcinoma/dysplasia (in ulcerative colitis);

Skin cancer (excluding melanoma, Merkel cell carcinoma);

Pregnancy exposure;

Infusion reaction associated with shortened infusion duration.
AESIs must be reported on the NIS AEM Report Form to Pfizer Safety within 24 hours 
of awareness.
10.1. Single Reference Safety Document
The EU-SmPC will serve as the single reference safety document (SRSD) during the course 
of the study, which will be used by Pfizer safety to assess any safety events reported to Pfizer 
Safety by the investigator during the course of this study. 
The SRSD should be used by the investigator for prescribing purposes and guidance.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 44 of 56
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
11.1. Reporting to Regulatory Agencies
All reports will be submitted to the regulatory authorities by Pfizer based on country/region 
reporting requirements and pursuant to required timeframes.
11.2. Use of Information and Publications
All data generated from this study are the property of Pfizer.  Pfizer shall have the right to 
publish such data and information without approval from the sites.  Pfizer will establish a 
uniform procedure for analysing, publishing, and disseminating findings from this study.  
Co-authors of publications may include participating physicians, Pfizer personnel, members 
of the National Leaders Committee, and/or other relevant thought leaders who contribute 
substantially to the publication.  Data from planned interim analyses will be published by 
Pfizer at time points deemed appropriate based on study progress.  Publications will adhere 
to the International Committee of Medical Journal Editors (ICMJE) guidelines.  Study data 
may not be published by participating sites without review and authorisation by Pfizer.
COMMUNICATION OF ISSUES
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this NI study protocol that the investigator becomes aware of.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 45 of 56
12. REFERENCES
1.
Last JM. A Dictionary of Epidemiology, 4th Edition.  Oxford University Press, 2001.
2.
Van den Brande, JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, 
Hoedemaeker C. et al., 2003.  Infliximab but not etanercept induces apoptosis in lamina 
propria T-lymphocytes from patients with Crohn’s disease.  Gastroenterology, 2003 Jun
124(7), pp.1774–1785.  Available at: 
http://linkinghub.elsevier.com/retrieve/pii/S0016508503003822 [Accessed May 22, 
2013].
3.
Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda H, et al.  A randomised, 
double-blind, multicentre, parallel-group, prospective study comparing the 
pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients 
with ankylosing spondylitis: the PLANETAS study.  Ann Rheum Dis 
2013Oct;72:1605–1612.
4.
Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuket S. et al.  A 
randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy
and safety of CT-P13 compared with innovator infliximab when coadministered with 
methotrexate in patients with active rheumatoid arthritis: the PLANETRA study.  Ann 
Rheum Dis; Published Online First: 21May2013.
5.
Harvey RF, Bradshaw JM.  A simple index of Crohn’s-disease activity.  Lancet. 1980
Mar;315(8167):514. 
6.
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, et al.  Infliximab for induction and 
maintenance therapy for ulcerative colitis.  N Engl J Med. 2005 Dec 8;353(23):2462-76.
7.
Irvine EJ, Zhou Q, Thompson AK.  The Short Inflammatory Bowel Disease 
Questionnaire: a quality of life instrument for community physicians managing 
inflammatory bowel disease.  CCRPT Investigators.  Canadian Crohn's Relapse 
Prevention Trial.  Am J Gastroenterol.  1996 Aug;91(8):1571-8.
8.
Reilly MC, Zbrozek AS, Dukes EM.  The validity and reproducibility of a work 
productivity and activity impairment instrument.  PharmacoEconomics 1993; 
4(5):353-65.
9.
International Conference on Harmonisation Harmonised Tripartite Guideline.  
Guideline for Good Clinical Practice: E6 (R1), Current Step 4 version.  1996 Jun 10.
10.
European Medicines Agency and Heads of Medicines Agencies.  Guideline on good 
pharmacovigilance practices (GVP) – Annex I (Rev 3) EMA/876333/2011 Rev 3.  
Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/
WC500143294.pdf.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 46 of 56
11.
International Committee of Medical Journal Editors.  Uniform requirements for 
manuscripts submitted to biomedical journals: writing and editing for biomedical 
publication.  Updated October 2008.  Available at: http://www.icmje.org/. 
13. LIST OF TABLES 
Table 1.
Study Data Collection Schedule
Table 2.
Observed AESI Rates
14. LIST OF FIGURES
Figure 1.
Study Design Schematic

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 47 of 56
APPENDICES
Appendix 1. Responsible Parties
A list of site Investigators is maintained in a stand-alone document and can be provided upon 
request.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 48 of 56
Appendix 2. Harvey Bradshaw Simple Index

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 49 of 56
Appendix 3. Partial Mayo Scoring System

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 50 of 56
Appendix 4. Summary of revised ‘Montreal Classification’ of Crohn’s Disease
Age at diagnosis (A)
A1 
16 years or younger 
A2 
17-40 years 
A3
Over 40 years 
Location (L)
Upper GI
modifier (L4)
L1 
Terminal ileum 
L1 + L4
Terminal ileum + Upper 
GI
L2 
Colon
L2 + L4
Colon + Upper GI 
L3
Ileocolon
L3 + L4
Ileocolon + Upper GI 
L4 
Upper GI 
-
-
Behaviour 
(B)
Perianal disease 
modifier (p)
B1*
Nonstricturing, 
nonpenetrating
B1p
Nonstricturing,
nonpenetrating + perianal
B2
Stricturing
B2p
Stricturing + perianal
B3
Penetrating
B3p
Penetrating + perianal
* B1 category should be considered 'interim' until a prespecified time has elapsed from the time of diagnosis.  
Such a time period may vary from study to study (eg, 5-10 years is suggested) but should be defined in order 
for B1 behaviour to be considered 'definitive'.  GI Gastrointestinal.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 51 of 56
Appendix 5. ‘Montreal Classification’ of Ulcerative Colitis
Key points 

A classification system for UC is proposed that incorporates: 

Disease extent; and 

Disease severity of individual acute relapses. 
Classification by extent 
UC can be defined by the extent of colorectal inflammation at a radiographic, endoscopic or 
histological level.  For the purposes of simplification, we propose that the extent of UC be 
defined by endoscopic appearance and by maximal extent during follow-up.  The three 
subgroups of UC defined by extent are: 
1. Ulcerative proctitis (E1): involvement limited to the rectum (ie, proximal extent of 
inflammation is distal to the rectosigmoid junction). 
2. Left-sided UC (E2) (also known as distal UC): involvement limited to the portion of 
the colorectum distal to the splenic flexure. 
3. Extensive UC (E3) (also known as pancolitis): involvement extends proximal to the 
splenic flexure. 
Classification by severity 
UC can be classified broadly into four disease activity/severity categories: 
1. UC in clinical remission (S0): No symptoms of UC. 
2. Mild UC (S1): in the classic description of disease activity by Truelove and Witts,1
this was defined as four or fewer bloody stools daily, lack of fever, pulse of less than 
90 beats/min, hemoglobin of 105 g/L or greater and erythrocyte sedimentation rate 
(ESR) of less than 30 mm/h.  A similar definition was given in the practice guidelines 
for management of UC recently published by the American College of 
Gastroenterology (ACG)2: four or fewer stools daily (with or without blood), no 
systemic signs of toxicity and a normal ESR. 
3. Moderate UC (S2): Truelove and Witts1 defined this as the state between mild and 
severe.  The ACG guidelines defined moderate disease as more than four stools daily 
but with minimal signs of systemic toxicity.2

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 52 of 56
4. Severe UC (S3): This was defined as the passage of at least six bloody stools daily, 
pulse of at least 90 beats/min, temperature of at least 37.5C, hemoglobin of less than 
105 g/L and ESR of at least 30 mm/h.1  The ACG guidelines defined severe colitis as 
at least six bloody stools daily and evidence of toxicity (fever, tachycardia, anemia or 
elevated ESR).2  The latter guidelines separated 'fulminant colitis' from 'severe'.  
Fulminant patients were those with at least 10 stools daily, continuous bleeding, 
toxicity, abdominal tenderness and distension, requirement for blood transfusion and 
colonic dilation on plain abdominal films.2
1.
Truelove SC, Witts LJ.  Cortisone in ulcerative colitis: final report on a therapeutic trial.  BMJ, 
1955;2:1041-1048.
2.
Kornbluth A, Sachar DB.  Ulcerative colitis practice guidelines in adults (update): American College of 
Gastroenterology, Practice Parameters Committee.  Am J Gastroenterol.  2004 Jul;99(7):1371-85.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 53 of 56
Appendix 6. Simple Fistula Assessment 
Fistula drainage assessment
Endpoints
Definition
Improvement
Remission
Improvement defined as a decrease from baseline in the number of open 
draining fistulae of ‡ 50%
for at least two consecutive visits (at least 4 weeks)
Remission defined as closure of all fistulae that were draining at baseline for at 
least two consecutive
visits (at least 4 weeks)
Closure of individual fistulae defined as no fistula drainage despite gentle finger 
compression.

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 54 of 56
Appendix 7. CT-P13: Summary of Product Characteristics
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/hu
man/002778/WC500151489.pdf

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 55 of 56
Appendix 8. Remicade: Summary of Product Characteristics
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/hu
man/000240/WC500050888.pdf

Infliximab
C1231001 NON-INTERVENTIONAL STUDY PROTOCOL
Final, Amendment Version 3.0, 06 October 2017
Page 56 of 56
Appendix 9. Optional Immunogenicity Data Collection
Study Population
For those sites that conduct immunogenicity analysis as part of their routine clinical care, 
there will be an option for enrolled CT-P13 patients to provide immunogenicity profile 
information as part of the data collection for the study.  Sites will document patient 
agreement for immunogenicity data collection.  The final immunogenicity analysis cohort 
will be a sample of the observational study population that opt to provide their 
immunogenicity results.  Patient participation in the CONNECT-IBD study is not contingent 
on participating in this immunogenicity data collection. There is no pre-determined sample 
size for the immunogenicity analysis.
Data Collection
Following enrolment into the CONNECT-IBD study, sites that conduct immunogenicity 
analysis as part of their routine clinical care may offer their CT-P13 patients the option to 
voluntarily provide their immunogenicity results as part of the data collection into the study 
EDC.  For CT-P13 patients who participate, data collection of immunogenicity results 
(including trough level as well as testing for anti-drug antibodies - ADA) of CT-P13 should 
be obtained from the most recent test results just prior to study enrolment, and at any time 
during patient study participation.  The immunogenicity data will only be described; there 
will be no attempt to draw an inference on similarity.  Since immunogenicity testing is 
conducted according to local routine practice, there is no specific data collection schedule.
Patients can withdraw their participation in the immunogenicity data collection at any time, 
and this will not affect their participation in the CONNECT-IBD study.  Sites will document 
withdrawal of participation.  However, patients who withdraw from the CONNECT-IBD 
study will automatically be discontinued from ongoing immunogenicity data collection.  
Pfizer reserves the right to terminate the optional immunogenicity analysis or the 
CONNECT-IBD study at any time.

'RFXPHQW $SSURYDO 5HFRUG
'RFXPHQW 1DPH
		 
  	  		
	
'RFXPHQW 7LWOH
		 
  	  		
	
6LJQHG %\
'DWH*07
6LJQLQJ &DSDFLW\
()*(	 ++,
-.%" .. %" //!01 !
	()*(	 ++3
-.%" .. %" //!01 !
PPD
PPD