A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate The Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants With Moderate To Severe Ulcerative Colitis
Phase: PHASE2
Conditions: Moderate to Severe Ulcerative Colitis
Sponsor: Hoffmann-La Roche

Official Title: 
A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-
Controlled Dose-Ranging Study to Evaluate the Efficacy, Safety, And 
Pharmacokinetics of PF-06480605 in Adult Participants with 
Moderate to Severe Ulcerative Colitis 
NCT Number: 
NCT04090411 
Document Date: 
Protocol Amendment Version 3: 15-Mar-2022 

B7541007
PFIZER CONFIDENTIAL
16.1.1. PROTOCOL
16.1.1.1. B7541007 Protocol Administrative Change Letter 19 August 2022
16.1.1.2. B7541007 Protocol Amendment 3 Clean 15 March 2022
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PFIZER CONFIDENTIAL 
CT02-GSOP-RF16 8.0 Protocol Administrative Change Letter (PACL) Template and Requirements 01-Apr-2022 
Page 1 of 2
19 Aug 2022 
RE:  Protocol Administrative Changes and Clarifications for Study B7541007, A Phase 2b, 
Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate 
the Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants with Moderate 
to Severe Ulcerative Colitis 
Dear Investigator, 
This Protocol Administrative Change Letter (PACL) is to notify you of the following 
administrative changes and clarifications to the B7541007 protocol; Protocol Amendment 3, 
March 15, 2022.   
The planned change is not considered substantial by Pfizer Inc. because there is no significant 
impact to the safety or physical or mental integrity of the trial participant, the scientific value of 
the trial, the conduct or management of the trial, or the quality or safety of any investigational 
medicinal product used in the trial, and therefore is not part of a formal amendment.  
As noted in Protocol Appendix 4, Section 10.4.4 Collection of Pregnancy Information, if a 
pregnancy occurs during the study, investigators are to follow the pregnancy until completion, 
assessing the structural integrity of the neonate at the time of birth. Further follow-up of birth 
outcomes is to be handled on a case-by-case basis. This PACL clarifies that part of the case-by-
case basis will include following the outcomes (for both the mother and the child) until 12 
months after delivery to ensure that an abnormal pregnancy outcome has not occurred. 
Accordingly, the following sentence in Appendix 4 is modified as indicated with additional text 
in bold font:  
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays) and will include following the 
outcomes for both the mother and the child for 12 months after delivery to ensure 
that a normal pregnancy outcome has occurred  
Rationale: 
Study drug PF-06480605 is a fully human neutralizing monoclonal antibody (mAb) in the early 
stages of clinical development. Presently, in pre-clinical studies in rabbits and mice 
(PF-06480605 
 June 2022 Version 5.0 Section 5.3.8) PF-06480605 
crosses the placental barrier but no toxicity was observed for embryo-fetal development, and 
clinical data is lacking. It is recognized that additional data on the effect of mAb exposure during 
pregnancy is required per FDA guidelines. The addition of the 12-month post-birth follow-up 
may assist with a better understanding of mAb exposure during pregnancy and satisfies FDA 
regulations.  
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A PHASE 2B, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED DOSE-RANGING STUDY TO EVALUATE THE 
EFFICACY, SAFETY, AND PHARMACOKINETICS OF PF-06480605 IN ADULT 
PARTICIPANTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS 
Investigational Product Number:
PF-06480605
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2019-002698-74
Protocol Number:
B7541007
Phase:
2B
SHORT TITLE: A study to evaluate the efficacy and safety of PF-06480605 in adult 
participants with moderate to severe ulcerative colitis
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 3
15 Mar 2022
The rationale for this protocol amendment 
is to incorporate changes from multiple 
previously written Protocol Administration 
Change Letter (PACL) 7, 8, 9, and 10. 
Typographical and spelling errors as well 
as cross references corrected throughout 
the document. 
Sections 1.1 Synopsis, 3.0 Objectives, 
Estimands, and Endpoints and 9.1.1 
Estimands: Modified estimands to permit 
exclusion of participants with missed visits
due to COVID–19 from analysis. Added 
Chronic Therapy Period secondary 
endpoint change from baseline for fecal 
calprotectin, hsCRP, and sTL1A 
biomarkers in order to better understand 
the full trajectory over time; tertiary 
endpoint for
to assess the impact of 
drug on a clinically meaningful threshold 
and more details around histopathology 
endpoints.  
Sections 1.1 Synopsis and 9.4.1 Efficacy 
Analyses: Modified analysis methods to 
align with similar analysis of binary 
endpoints, and to allow comparison with 
historical data from other studies and 
publications with similar endpoints on 
treatment effect.
Sections 1.1 Synopsis, 9.5 Interim 
Analyses and 9.5.1 Data Monitoring 
Committee: Modified first interim analysis 
language to 100% of participants, second 
interim analysis to approximately 100% of 
participants, and removed futility 
assessment by IRC due to quicker than 
expected enrollment. Included Pfizer 
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template language regarding how IRC 
recommendations will be processed.
Sections 1.1 Synopsis, 1.3 SoA footnote 
“u”, 4.1 Overall Design, 
7.1 Discontinuation of Study Intervention, 
7.2 Participant Discontinuation/
Withdrawal from Study, and 
8.1.1 Colonoscopy/Sigmoidoscopy: 
Modified language to clarify participants 
who withdraw from the treatment period 
should be followed for 3 study visits (one 
being the Early Withdrawal Visit) for a 
total of 12 weeks from the last dose of 
investigational product. 
Section 1.3 Scheduled of Activities (SoA): 
Removed return stool diary data collection 
tool from Early Withdrawal visit due to 
administrative error.
Sections 1.3 SoA footnote “v”, 
8.2.6 Hepatitis, and Appendix 2.1: Altered 
reference from Appendix 2.1 to 
Section 8.2.6 in SoA footnote “v”, 
modified language in Section 8.2.6 to align 
with footnote “v” and incorporate 
Appendix 2.1 language, and removed 
Appendix 2.1 to clarify Hepatitis B study 
requirements. 
Section 7.2: Modified language to clarify 
when protocol deviations are not required 
for early withdrawal procedures.
Section 9.3 Populations for Analysis: 
Updated Evaluable Population to include 
Intention–To–Treat (ITT) and modified 
Intention–To–Treat (mITT) in order to 
distinguish between Induction and Chronic 
Period, and provided clarification for 
Biomarker Analysis Population and 
clarified biomarker analysis population. 
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Section 9.4.2.1 Adverse Events: Modified 
safety endpoint language to align with 
updated Pfizer Data Standards.
Country Specific:
Appendix 15 Alternative Measures During 
Public Emergencies: Added alternative 
approach language to home health visits 
for Germany and Japan.
Amendment 2
01 Sep 2020
The rationale for this protocol amendment 
is to incorporate non-substantial changes 
from multiple previously written PACL 1, 
2, 3, 4, 5, and 6. The most current revision 
is noted in the protocol.
Typographical and spelling errors as well 
as cross references corrected throughout 
the document.
Sections 1.1, 3.0 and 9.1.1: Clarified 
estimands regarding primary induction and 
chronic therapy period, related to what is 
considered a non responder regarding 
early treatment discontinuation.
Estimands section updated to reflect and 
clarify how a patient who discontinues 
study treatment prior to week 12 will be 
allocated regarding responder and non 
responder. 
Section 1.3 Schedule of Activities
Changes implemented:  
Hep Virus, chest x-ray, colonoscopy, 
participant stool diary updates within table 
and/or footnotes.
Urine drug screen as indicated in 
Appendix 2.
Fecal microbiome and fecal metabolomics 
will be collected at screening prior to the 
bowel preparation, (not Visit 1).  Fecal 
calprotectin, fecal microbiome and fecal 
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metabolomics will be collected at the early 
Withdraw Visit, to collect final specimens 
if participant withdraws.
Serum protein profiling to be collected at 
Visit 17, was inadvertently removed 
during formatting.
Blood for PBMC single cell sequencing
removed Week 4, 12, 28, 52, and 60 as no 
longer required.
The letter “g” was removed from Study 
Visits 1 and 15 for Injection Site 
Reactions, as reference to the footnote is 
provided in the Treatment Procedure 
column of the table.
Targeted medical exam removed at Visit 
15 as complete physical exam is required 
and already present.
Footnote “w” added to Day 1 (baseline) 
to clarify that participants should 
select option for “no change” since starting 
the study medication.
Footnote “x” added to banked 
biospecimens that if not collected on the 
designated day to collect at the next 
scheduled visit.
Partial Mayo Score: The Partial Mayo 
Score is comprised of the sum of the 
participant’s stool frequency, rectal 
bleeding and physician’s global 
assessment, (PGA). While it is necessary 
for the participant to collect
stool 
frequencies, and rectal bleeding during the 
screening period, the PGA should not be 
assessed until Day 1. Therefore the 
schedule of assessments table will have 
Partial Mayo Score assessment “X” 
removed at screening.  
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Dispensing of stool kits will be removed at 
study Visits 4 and 15.
Section 1.3, Schedule of Activities, and/or
Section 8.8.10.1, Exploratory Banked 
Biospecimens; Prep B1.5 and Prep B2.5 
changed to Prep B1 and Prep B2 as this 
represents the larger collection tubes. 
Other Changes throughout the protocol: 
Section 5.1, Inclusion Criterion Weight, 
BMI removed as investigational drug is 
not dosed based on weight.
Section 5.2, Exclusion Criterion #17: 
Corrected error in expressing unit 
conversion for both ALC and ANC. 
Section 6.1:
Added to Table 4: see investigational 
product manual for dosing.
Section 6.2.1: Preparation and Dispensing: 
Protocol wording changed from 
“administered to blinded participants” to 
“will be administered in a blinded manner 
to participants.”
Section 6.2.1, Preparation and Dispensing: 
corrected text from “investigational 
product will be dispensed using an IRT 
system for each visit from Visit 1 to 
Visit 15” to “investigational product will 
be dispensed using an IRT system from 
Visit 1 to Visit 15 with the exception of 
Visit 5.”
Sections 6.5 and 8.1.7: Added anti-IL 
12/23 to the list of conmeds to be 
consistent with inclusion criterion #5.
Section 6.5.1: Added clarifications to the 
wording under permitted medications.
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Section 8.1.1: Updated the order of the 
biopsies to be collected to be consistent 
between both paragraphs.
8.1.1: Provided enhanced instructions on 
activating Trialweb at Visit 5 or Visit 16.
Section 8.2.3: added “or an expert of lung 
disease” in addition to qualified 
radiologist.
Section 1.3, 8.2.6 and Appendix 2
Hepatitis results clarified.
Section 8.3:Updates to May 2020 
template.
Section 8.3.1 Time period for collecting 
AE and SAE information: Protocol 
wording states, “through and including 
Visit 20”; this is corrected to Visit 18. 
Section 8.3.7 Updated section to 
May 2020 template and added information 
related to lack of efficacy.
Section 1.1 and 9.4.1: Efficacy Analyses:
Additional details provided for estimating 
the odds ratio and associated 2 sided 90% 
confidence intervals.
Section 10.1.3 and 8.3, removed legally 
acceptable representative throughout the 
section, as all participants must be able to 
read to answer the
electronic diary.
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Appendix 8, Prohibited Medications: 
Clarified text regarding prohibited 
corticosteroid doses. 
Appendix 8, 
 
Changed to “Prohibited Time Period”.
Appendix 8, Prohibited concomitant 
medications: 
Appendix 8, Prohibited concomitant 
medications: 
Country specific:
Appendix(s) 8 and 9, Prohibited and 
Permitted Medications Clarifications 
completed to make the time required to be 
off of prohibited drugs and established 
time required for stable dosing.
Appendix 10, Updated Mayo Scoring 
system for assessment of ulcerative colitis: 
the modified endoscopic scoring system 
will be used in this study.  Friability was 
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removed from endoscopic subscore of 
1 and placed into the endoscopic subscore 
2.
Added Appendix 15: Alternative measures 
to be taken during public emergencies; 
added to note alternative methods may be 
used to continue the currently enrolled 
participants in the study, in case of a 
resurgence of COVID-19.
Amendment 1 
10 Feb 2020
Japan Country Specific Amendment: 
Added HBV DNA testing at screening and 
(if applicable every 12 weeks during 
treatment) per PMDA Regulations.
HBV DNA testing was added to 
Section 1.3, (added HBV testing to 
footnote “m” to be performed locally and 
added footnote “v” specific to Japan 
participants).  Added HBV DNA testing to 
section 8.2.6, Appendix 2 (Table 5) and 
Appendix 2.1. 
Added HBV DNA testing to abbreviations.
Original protocol
18 July 2019
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................16
1. PROTOCOL SUMMARY...................................................................................................17
1.1. Synopsis ..................................................................................................................17
1.2. Schema ....................................................................................................................24
1.3. Schedule of Activities (SoA)...................................................................................25
2. INTRODUCTION ...............................................................................................................32
2.1. Study Rationale .......................................................................................................32
2.2. Background .............................................................................................................33
2.2.1. Clinical Overview.......................................................................................34
2.2.1.1. Clinical Safety...........................................................................34
2.2.1.2. Clinical Pharmacokinetics.........................................................36
...........................................................37
2.3. Benefit/Risk Assessment.........................................................................................37
2.3.1. Overall Risk-Benefit Assessment for Study...............................................37
2.3.2. Potential Benefits........................................................................................38
2.3.3. Potential Risks ............................................................................................38
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................39
4. STUDY DESIGN.................................................................................................................46
4.1. Overall Design.........................................................................................................46
4.2. Scientific Rationale for Study Design.....................................................................47
4.3. Justification for Dose ..............................................................................................48
4.4. End of Study Definition ..........................................................................................49
5. STUDY POPULATION......................................................................................................49
5.1. Inclusion Criteria.....................................................................................................50
5.2. Exclusion Criteria....................................................................................................51
5.3. Lifestyle Considerations..........................................................................................53
5.3.1. Contraception..............................................................................................53
5.4. Screen Failures ........................................................................................................54
6. STUDY INTERVENTION..................................................................................................54
6.1. Study Intervention(s) Administered........................................................................54
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6.1.1. Administration............................................................................................55
6.2. Preparation/Handling/Storage/Accountability ........................................................56
6.2.1. Preparation and Dispensing........................................................................57
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................57
6.3.1. Allocation to Investigational Product .........................................................57
6.3.2. Breaking the Blind......................................................................................58
6.4. Study Intervention Compliance...............................................................................58
6.5. Concomitant Therapy..............................................................................................58
6.5.1. Permitted Medications................................................................................59
6.5.2. Prohibited Medications...............................................................................59
6.5.3. Rescue Medication......................................................................................60
6.6. Dose Modification...................................................................................................60
6.7. Intervention After the End of the Study..................................................................60
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................60
7.1. Discontinuation of Study Intervention ....................................................................60
7.1.1. Criteria for Discontinuation........................................................................61
7.2. Participant Discontinuation/Withdrawal From the Study.......................................61
7.3. Lost to Follow-up....................................................................................................62
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................63
8.1. Efficacy Assessments..............................................................................................63
8.1.1. Colonoscopy/Sigmoidoscopy .....................................................................63
8.1.2. Total Mayo Score .......................................................................................65
8.1.3. Participant Stool Diary ...............................................................................66
8.1.4. Partial Mayo Score .....................................................................................67
8.1.5. UC Medical History (Screening)................................................................67
8.1.6. Medical History (Screening).......................................................................67
8.1.7. Prior Medications (Screening)....................................................................67
8.1.8. Patient Reported Outcomes ........................................................................67
8.1.9. Rater Qualifications....................................................................................68
8.1.10. Imaging Assessments................................................................................68
8.2. Safety Assessments .................................................................................................69
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8.2.1. Physical Examinations, Height and Weight ...............................................69
8.2.1.1. Complete Physical Examinations..............................................69
8.2.1.2. Targeted Physical Examinations ...............................................69
8.2.2. Vital Signs ..................................................................................................69
8.2.3. Chest X-Ray or Chest Computerized Tomography, (CT)(Screening 
only).................................................................................................................70
8.2.4. Interferon Gamma Release Assay Tuberculin Test (Screening only) ........70
8.2.5. HIV (Screening only) .................................................................................70
8.2.6. Hepatitis......................................................................................................71
8.2.7. Active Enteric Infections (Positive Stool culture and sensitivity) 
(Screening only)...............................................................................................72
8.2.8. Electrocardiograms.....................................................................................72
8.2.9. Injection Site Reactions..............................................................................72
8.2.10. Contraception Checks...............................................................................73
8.2.11. Clinical Safety Laboratory Assessments ..................................................73
8.2.12. Pregnancy Testing ....................................................................................73
8.3. Adverse Events and Serious Adverse Events..........................................................74
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......74
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................75
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................75
8.3.2. Method of Detecting AEs and SAEs ..........................................................75
8.3.3. Follow-up of AEs and SAEs.......................................................................75
8.3.4. Regulatory Reporting Requirements for SAEs...........................................76
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................76
8.3.5.1. Exposure During Pregnancy......................................................76
8.3.5.2. Exposure During Breastfeeding ................................................76
8.3.5.3. Occupational Exposure .............................................................77
8.3.6. Medication Errors .......................................................................................77
8.3.7. Lack of Efficacy .........................................................................................78
8.4. Treatment of Overdose............................................................................................78
8.5. Pharmacokinetics ....................................................................................................78
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8.5.1. Serum for Analysis of PF-06480605..........................................................78
8.5.2. Analysis of Anti-PF-06480605 Antibodies and Neutralizing 
Anti-PF-06480605 Antibodies.........................................................................79
8.5.3. Exploratory Immunogenicity Peripheral Blood Mononuclear Cell 
(PBMC) Samples .............................................................................................80
8.5.4. Exploratory Analysis of ADA Epitopes/Affinities.....................................80
8.6. Pharmacodynamics..................................................................................................80
8.7. Genetics...................................................................................................................80
8.7.1. Specified Genetics ......................................................................................80
8.7.2. Banked Biospecimens for Genetics............................................................80
8.8. Biomarkers ..............................................................................................................81
.............81
.............81
.............81
.............82
.............82
.............82
.............82
.............82
.............82
.............82
.............83
.............83
.............83
.............83
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8.9. Health Economics ...................................................................................................84
9. STATISTICAL CONSIDERATIONS ................................................................................84
9.1. Estimands and Statistical Hypotheses.....................................................................84
9.1.1. Estimands....................................................................................................84
9.2. Sample Size Determination.....................................................................................85
9.3. Populations for Analysis .........................................................................................86
9.4. Statistical Analyses .................................................................................................86
9.4.1. Efficacy Analyses .......................................................................................87
9.4.2. Safety Analyses ..........................................................................................87
9.4.2.1. Adverse Events..........................................................................87
9.4.2.2. Electrocardiogram Analyses......................................................88
9.4.3. Other Analyses............................................................................................88
9.4.3.1. Pharmacokinetic Analysis.........................................................88
..................................................................88
9.4.3.3. PK/PD Unblinding Plan ............................................................88
9.4.3.4. Immunogenicity Analysis .........................................................89
9.5. Interim Analyses .....................................................................................................89
9.5.1. Data Monitoring Committee.......................................................................89
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................91
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............91
10.1.1. Regulatory and Ethical Considerations ....................................................91
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................91
10.1.2. Financial Disclosure .................................................................................92
10.1.3. Informed Consent Process ........................................................................92
10.1.4. Data Protection .........................................................................................93
10.1.5. Dissemination of Clinical Study Data ......................................................93
10.1.6. Data Quality Assurance ............................................................................95
10.1.7. Source Documents....................................................................................96
10.1.8. Study and Site Closure..............................................................................96
10.1.9. Publication Policy.....................................................................................97
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10.1.10. Sponsor’s Qualified Medical Personnel .................................................97
10.2. Appendix 2: Clinical Laboratory Tests .................................................................99
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................100
10.3.1. Definition of AE .....................................................................................100
10.3.2. Definition of SAE...................................................................................101
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.....................102
10.3.4. Reporting of SAEs..................................................................................105
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..............................................................................................................107
10.4.1. Male Participant Reproductive Inclusion Criteria..................................107
10.4.2. Female Participant Reproductive Inclusion Criteria...............................107
10.4.3. Woman of Childbearing Potential (WOCBP) ........................................107
10.4.4. Contraception Methods...........................................................................108
........................................................................................111
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......112
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................114
10.8. Appendix 8: Prohibited Concomitant Medications.............................................116
10.9. Appendix 9: Permitted Concomitant Medications for UC..................................118
10.10. Appendix 10: Mayo Scoring System for Assessment of Ulcerative Colitis .....119
.................................................................................120
.................................................................................124
.................................................................................131
.................................................................................132
10.15. Appendix 15 Alternative Measures During Public Emergencies......................144
10.15.1. Telehealth Visits (if applicable)............................................................144
10.15.2. Home Health Visits (If applicable).......................................................144
10.15.3. Laboratory Testing: (If applicable).......................................................145
10.15.4. Electrocardiograms (If applicable) .......................................................146
10.15.5. Adverse Events and Serious Adverse Events.......................................146
10.16. Appendix 16: Abbreviations .............................................................................147
17 REFERENCES .................................................................................................................152
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LIST OF TABLES  
Table 1.
View of the Schematic..............................................................................24
Table 2.
Treatment Sequence..................................................................................47
.......49
Table 4.
Study Intervention(s) Administered .........................................................54
Table 5.
Protocol Required Safety Laboratory Assessments..................................99
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1. PROTOCOL SUMMARY 
1.1. Synopsis
Short Title: A study to evaluate the efficacy and safety of PF-06480605 in adult participants 
with moderate to severe ulcerative colitis.
Rationale:
Treatment with PF-06480605 was safe and well tolerated in a Phase 1 study in healthy 
participants and a Phase 2a study in participants with moderate to severe active Ulcerative 
Colitis, (UC). Furthermore, PF-06480605 was efficacious in treatment of UC. 
This Phase 2b, multicenter, randomized, double-blind, placebo-controlled dose-ranging study 
examines varying subcutaneous, (SC) doses of investigational product, (IP) administered 
every 4 weeks in participants with moderate to severe active UC to characterize safety, 
efficacy, pharmacokinetics (PK), and immunogenicity and to inform subsequent Phase 3 
design.
Objectives, Estimands, and Endpoints Primary and Secondary Endpoints
Objectives
Endpoints
Estimands
Induction Period: Primary

To evaluate the efficacy
of PF-06480605 in 
induction of clinical 
remission at Week 14 in 
participants with 
moderate to severe 
active UC.

Proportion of participants 
achieving clinical remission 
(defined as a Total Mayo Score 
≤2, with no individual subscore
>1) at Week 14.
E1: This estimand is defined as a 
population average treatment 
difference between PF-06480605 and
placebo in the proportion of 
participants who met the binary 
endpoint without discontinuing 
treatment prior to Week 12 visit.
Treatment: PF-06480605, Placebo.
Population: Participants with 
moderate to severe active UC as 
defined by inclusion/exclusion 
criteria.
Variable: clinical remission at 
Week 14. 
Intercurrent Events: Treatment 
discontinuation prior to Week 12 
visit. If a study participant 
discontinued the treatment prior to 
Week 12 visit but didn’t attend the 
early withdrawal visit, the participant 
will be considered as a non-responder 
for the binary remission endpoint at 
Week 14 for the primary analysis
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unless reason for missed visit was 
due to COVID-19.
Population level summary: treatment 
difference between PF-06480605 and
placebo in proportions of responders 
using the binary endpoint.

To evaluate the safety 
and tolerability of 
PF-06480605 during the 
induction period (from 
baseline to Week 14) in 
participants with 
moderate to severe 
active UC.

Incidence and severity of 
treatment emergent adverse 
events (TEAEs) during the 
induction period.

Incidence of serious adverse 
events (SAEs) during the 
induction period.

Incidence of AEs or SAEs leading 
to discontinuation during the 
induction period.

Incidence of clinically significant 
abnormalities in vital signs, 
electrocardiograms, (ECGs) and 
laboratory values during the 
induction period.
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
Induction Period: Secondary

To evaluate the efficacy 
of PF-06480605 in 
inducing remission at 
Week 14 in participants 
with moderate to severe 
active UC.

Proportion of participants 
achieving remission Food and 
Drug Administration, ((FDA)
definition 1 - defined as 
endoscopic subscore = 0 or 1, 
stool frequency subscore = 0, and 
rectal bleeding subscore = 0) at 
Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

Proportion of participants 
achieving remission (FDA 
definition 2 - defined as 
endoscopic subscore = 0 or 1, 
≥1-point decrease from baseline 
to achieve a stool frequency 
subscore = 0 or 1, and rectal 
bleeding subscore = 0) at 
Week 14. 
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

To evaluate the efficacy 
of PF-06480605 on 
endoscopic appearance 
at Week 14 in 
participants with 

Proportion of participants 
achieving endoscopic 
improvement (defined as 
endoscopic subscore = 0 or 1) at 
Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.
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moderate to severe 
active UC during the 
induction period.

Proportion of participants 
achieving endoscopic remission 
(defined as endoscopic 
subscore = 0) at Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

To characterize the PK 
of PF-06480605 in 
participants with 
moderate to severe 
active UC during the 
induction period.

PF-06480605 trough 
concentrations during the 
induction period through 
Week 14.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To evaluate disease and 
pathway related 
biomarkers (ie, hsCRP 
and fecal calprotectin 
and serum sTL1A) 
during the induction 
period.

Change from screening in fecal 
calprotectin during the induction 
period through Week 14. 

Change from baseline in hsCRP 
during the induction period 
through Week 14.

Change from baseline in serum 
sTL1A during the induction 
period through Week 14.
There is no defined estimand for
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To characterize the 
immunogenicity of 
PF-06480605 in 
participants with 
moderate to severe 
active UC during the 
induction period.

Incidence of development of 
anti-drug antibodies (ADAs) and 
neutralizing antibodies (NAbs) 
during the induction period 
through Week 14.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
Chronic Therapy Period - Primary

To evaluate the safety 
and tolerability of 
PF-06480605 during the 
chronic therapy period 
(from Week 14 to the 
End of Study Visit) in 
participants with 
moderate to severe 
active UC during the 
chronic therapy period.

Incidence and severity of 
treatment emergent adverse 
events (TEAEs) during the 
chronic therapy period.

Incidence of serious adverse 
events (SAEs) during the chronic 
therapy period.

Incidence of AEs or SAEs leading 
to discontinuation during the 
chronic therapy period.

Incidence of clinically significant 
abnormalities in vital signs, ECGs 
and laboratory values during the 
chronic therapy period.
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
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Chronic Therapy Period – Secondary

To evaluate the efficacy 
of chronic therapy of 
PF-06480605.

Proportion of participants 
achieving clinical remission 
(defined as a Total Mayo Score 
2, with no individual subscore
>1) at Week 56. 
E2: This estimand is defined as a 
population average treatment 
difference between PF-06480605 and 
placebo in the proportion of 
participants who met the binary 
endpoint without discontinuing 
treatment prior to Week 52 Visit.
Treatment: PF-06480605, Placebo.
Population: Participants with 
moderate to severe active UC as 
defined by inclusion/exclusion 
criteria, and participants who met the 
binary endpoint at Week 14 but did 
not continue to the chronic therapy 
period will be excluded. 
Variable: Clinical Remission at 
Week 56. 
Intercurrent Events: Treatment 
discontinuation prior to Week 52 
Visit. If a study participant 
discontinued the treatment prior to 
Week 52 Visit but didn’t attend the 
early withdrawal visit, the participant 
will be considered as a non-responder 
for the binary remission endpoint at 
Week 56 for the secondary analysis
unless reason for missed visit was 
due to COVID-19.
Population level summary: treatment 
difference between PF-06480605 and
placebo in proportions of responders 
using the binary endpoint.

Proportion of participants 
achieving sustained clinical 
remission (ie, clinical remission at 
both Week 14 and Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is sustained 
clinical remission.

Proportion of participants 
achieving remission (FDA 
definition 1 - defined as 
endoscopic subscore = 0 or 1, 
stool frequency subscore = 0, and 
rectal bleeding subscore = 0) at 
Week 56.

Proportion of participants 
achieving sustained 
remission-FDA definition 1 
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is remission 
(FDA definition 1) at Week 56 or 
sustained remission (FDA 
definition 1).
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(ie, remission-FDA definition 1 at 
both Week 14 and Week 56).

Proportion of participants 
achieving remission (FDA 
definition 2 - defined as 
endoscopic subscore = 0 or 1, 
≥1-point decrease from baseline 
to achieve a stool frequency 
subscore = 0 or 1, and rectal 
bleeding subscore = 0) at 
Week 56.

Proportion of participants 
achieving sustained 
remission-FDA definition 2 
(ie, remission-FDA definition 2 at 
both Week 14 and Week 56).  
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is remission 
(FDA definition 2) at Week 56 or 
sustained remission (FDA 
definition 2).

Proportion of participants 
achieving endoscopic 
improvement (defined as 
endoscopic subscore = 0 or 1) at 
Week 56.

Proportion of participants 
achieving sustained endoscopic 
improvement (ie, endoscopic 
improvement at both Week 14 
and Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is endoscopic 
improvement at Week 56 or sustained 
endoscopic improvement.

Proportion of participants 
achieving endoscopic remission 
(defined as endoscopic 
sub-score = 0) at Week 56.

Proportion of participants 
achieving sustained endoscopic 
remission (ie, endoscopic 
remission at both Week 14 and 
Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is endoscopic 
remission at Week 56 or sustained 
endoscopic remission. 

To characterize the PK 
of PF-06480605 in 
participants with 
moderate to severe UC 
during the chronic 
therapy period.

PF-06480605 concentration from 
Week 14 through the End of 
Study Visit.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To evaluate disease and 
pathway related 
biomarkers (ie, hsCRP 
and fecal calprotectin 
and serum sTL1A during 

Change from Week 14 in fecal 
calprotectin during the chronic 
therapy period through the End of 
Study Visit. 
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
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Overall Design
This is a Phase 2b multi-center, parallel group, placebo-controlled, double-blind, randomized 
study in participants with moderate to severe active UC. An internal review committee will 
be used.
Number of Participants
A maximum of approximately 240 participants will be randomly assigned to investigational 
product, such that approximately 216 evaluable participants complete the study.
Intervention Groups and Duration
This study will occur over 4 periods; screening, induction, chronic therapy and follow-up.  
The first screening period may last up to 6 weeks to assess eligibility. During the 12-week 
induction period, participants will receive 50 mg, 150 mg, 450 mg, or matched placebo by 
subcutaneous administration every 4 weeks. During the 40-week chronic therapy period, all 
participants will receive active drug: 50 mg, 150 mg, or 450 mg by subcutaneous
administration every 4 weeks.  During the 12-week follow-up period, final safety 
assessments will be made. The final follow-up period will be 12 weeks in duration. Overall 
the study participation for each participant will be up to 70 weeks. Participants that 
discontinue at any time during the study will proceed into the follow-up period with an early 
withdrawal visit. Any participant who prematurely withdraws from the treatment period 
the chronic therapy 
period.

Change from Week 14 in hsCRP 
during the chronic therapy period 
through the End of Study Visit.

Change from week 14 in serum 
sTL1A during the chronic therapy 
period through the End of Study 
Visit.

Change from baseline through the 
End of the Study Visit in fecal 
calprotectin.

Change from baseline through the 
End of the Study Visit in hsCRP.

Change from baseline through the 
End of Study Visit in serum 
sTL1A.

To characterize the 
immunogenicity of 
PF-06480605 in 
participants with 
moderate to severe UC 
during the chronic 
therapy period.

Incidence of development of 
anti-drug antibodies (ADAs) and 
neutralizing antibodies (NAbs) 
from Week 14 through the End of 
Study Visit.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
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(after being randomized and during active study intervention) should be followed for 3 study 
visits (one being the Early Withdrawal Visit) for a total of 12 weeks from the last dose of 
interventional product.
Data Monitoring Committee 
This study will use an internal review committee (IRC). An external data monitoring 
committee will not be utilized. An IRC charter will be developed to govern the details of any  
IRC operations.
Statistical Methods
The primary estimand for the primary endpoint of clinical remission at Week 14 will be the 
population average treatment difference between PF-06480605 and placebo in the proportion 
of participants with moderate to severe active ulcerative colitis who achieve the binary 
remission endpoint without discontinuing treatment prior to the Week 12 Visit. If a study 
participant discontinues treatment prior to Week 12 Visit but did not attend the early study 
withdrawal visit, then the participant will be considered as a non-responder for the primary 
analysis unless reason for missed visit was due to COVID-19.
The primary endpoint of this study is the proportion of participants achieving clinical 
remission at Week 14.  The proportions responding and the risk difference between the 
treatment arms and the placebo arm will be analyzed using an unconditional exact method: 
risk differences and corresponding 2 sided unconditional exact 90% confidence intervals will 
be computed using the Chan and Zhang24 method.
Two interim analyses may be conducted for the study. The first analysis will be conducted 
when 100% of participants have completed or have the opportunity to complete the Week 14 
Visit.  The second interim analysis may be conducted when all participants have completed 
or have the opportunity to complete the induction period and approximately 100% of them 
have completed or have the opportunity to complete at least 6 months of chronic therapy. 
Interim analysis results may be used for internal decisions regarding future study planning. 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined in Section 9 and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.
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1.2. Schema
Table 1.
View of the Schematic
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t.
At dosing visits, samples will be collected preferably after vital signs data and within approximately 30 minutes prior to SC dosing.
u.
Any participant who prematurely withdraws from the treatment period (after being randomized and taking IP) should be followed for 12 weeks from the 
last dose of investigational product. The Early Withdrawal Visit replaces Visit 16 (see Section 7.1).
v.
For participants who enroll from Japan or countries where DNA testing is required for Hepatitis: Participants who are negative for all 3 serology tests may 
be eligible.  Participants who are HBsAg positive will be excluded; participants who are HbsAg negative, HBcAb positive and HBsAb negative will be 
excluded. Participants who are HBsAg negative, HBcAb negative, and HBsAb positive and provide documentation of prior HBV vaccination, may be 
eligible for the study and will not require HBV DNA monitoring during the study.  Participants who are HBsAg negative, HBcAb negative, and HBsAb 
positive without documentation of prior HBV vaccination AND participants who are HBsAg negative, HBcAb positive, and HBsAb positive, will have 
HBV DNA assessed at screening.  If HBV DNA is detectable, participants will be excluded.  If HBV DNA is not detectable, participants may be eligible.  
If enrolled, HBV DNA will also be assessed at Week 12 and repeated every 12 Weeks: Also see Section 8.2.6.
w.
Participant to mark “no change” for Day 1
 as the question is not applicable to Day 1.
x.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit.
y.
Coagulation tests, PT/PTT/INR will be collected at screening, Week 12, and Week 52. 
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2. INTRODUCTION
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal
tract that affects 5 million people worldwide. IBD presents as 1 of 2 major forms, ulcerative 
colitis (UC) or Crohn’s disease (CD). UC is characterized by continuous inflammation that 
is localized to the colon. Medical therapy is available, but surgical resection of the entire 
colon can provide a definitive cure. CD is characterized by discontinuous inflammation that 
affects the entire gastrointestinal tract from mouth to anus and long-term debilitating 
sequelae, such as fistulae and intestinal strictures.  Although the exact causes of UC and CD
remain unclear, inhibition of pro-inflammatory cytokines and adhesion molecules have 
proven to deliver some therapeutic benefit. 
The incidence of UC reported in the past 20 years varies by location.  Reported rates in North 
America range from about 8-19, in South America from 1.5-2.6, in Asia and the Middle East 
from 0.6-4.4, in Western Europe from 2.3-17.5, in Eastern Europe from 0.8-5.9, and in 
Australia/New Zealand, from 7.6-17.4 per 100,000 person-years.  The prevalence of UC in 
the same time period, by geographic region, ranged from 155.8-248.6 in North America, was 
76.1 in a single report from South America, from 4.9-168.3 in Asia and the Middle East, 
from 4.9-294 in Northern and Western Europe, from 2.42-101 in Eastern Europe and 145 in 
Australia and New Zealand per 1,000,000 persons.  Globally there does not appear to be a 
gender difference in incidence of UC.1
Although UC can occur at any age, the incidence peaks between 15 to 25 years with a second 
peak between 55 to 65 years.2 UC is a lifelong condition with a serious effect on the quality 
of life. 
Current IBD treatments include aminosalicylates, corticosteroids, immunosuppressants, 
monoclonal antibodies against tumor necrosis factor (TNF)-or 47 integrin, and JAK 
inhibitors.  Despite multiple therapies being available, limitations remain in the treatment of 
IBD, and patients continue to have symptoms or develop intolerance to or side effects from 
their treatment regimens. 
The investigational product (IP) PF-06480605 is a fully human neutralizing monoclonal 
antibody against TL1A currently in development for the treatment of IBD. The mechanism 
of action of PF-06480605 is to neutralize the binding and subsequent signaling of TL1A to 
its functional receptor DR3 on immune cells of the innate and adaptive immune system. 
2.1. Study Rationale
Treatment with PF-06480605 was safe and well tolerated in a Phase 1 study in healthy 
participants and a Phase 2a study in participants with moderate to severe active UC. 
Furthermore, PF-06480605 was efficacious in treatment of UC. 
This Phase 2b, multicenter, randomized, double-blind, placebo-controlled dose-ranging study 
examines varying SC doses of IP administered every 4 weeks in participants with moderate 
to severe active UC to characterize safety, efficacy, pharmacokinetics (PK), and 
immunogenicity and to inform subsequent Phase 3 design.
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2.2. Background
The tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the 
TNFSF15 gene, is a cytokine implicated in wide-ranging pro-inflammatory and pro-fibrotic 
processes.3 TL1A mediates immune effects through its cognate receptor, Death Receptor 3 
(DR3) (TNFRSF25). TL1A can also bind a soluble decoy receptor, DcR3 (TNFRSF6B),
which also interacts with LIGHT (TNFSF14) lymphotoxin-related inducible ligand and Fas 
ligand. TL1A is commonly expressed under pro-inflammatory conditions on monocytes, 
macrophages, and dendritic cells (DCs), whereas DR3 is primarily expressed on T cells, NK 
cells, and innate lymphoid cells (ILCs), and possibly to a lesser degree also on B cells and 
macrophages.3
TL1A has been reported to play a central role in amplification of a broad spectrum of 
inflammatory responses. For instance, TL1A promotes interleukin, (IL)-2 signaling in 
T cells by simultaneously increasing IL-2 production and expression of IL-2RA and 
IL-2RB.4,5 TL1A acts in synergy with IL-12, IL-15, and IL-18 on T cells and natural killer, 
(NK) cells to produce multiple cytokines, including interferon gamma, (IFN-), IL-6, IL-13, 
and granulocyte-macrophage colony-stimulating factor, (GM-CSF).6,7 Furthermore, TL1A 
has been shown to have costimulatory effect on ILCs, where TL1A synergizes with IL-25 
and IL-33 in stimulating the secretion of IL-5 and IL-13 from ILC2s,8 and with IL-1and 
IL-23 to induce IL-22 secretion from ILC3s.9
Human genetic evidence first highlighted a potentially critical role for TL1A in IBD 
pathogenesis. An initial genome wide association studies (GWAS) in a Japanese cohort 
implicated 12 single nucleotide polymorphisms (SNPs) in the TNFSF15 gene as CD risk 
alleles.10 5 of these SNPs were validated as risk alleles in a subsequent United Kingdom, 
(UK) cohort.10 Many TNFSF15 GWAS studies have since emerged. A recent meta-analysis 
of 15 such studies demonstrated that 6 different SNPs are significantly associated with CD, 
while 3 SNPs are significantly associated with UC.11  Additionally, SNPs in the decoy 
receptor TNFRSF6B gene (DcR3) have been shown to be a risk factor for pediatric IBD.12,13  
One of these TNFSF15 risk alleles is associated with diagnosis at the age of 16 or younger, 
ileocolonic location, and stricturing or penetrating behavior in a Japanese CD cohort.14
Follow-up human studies have further corroborated the potentially critical role for TL1A in 
IBD pathogenesis. TL1A expression studies have demonstrated high expression levels of 
TNFSF15 (TL1A) gene in the inflamed intestinal mucosa of patients with CD, when 
compared to their non-inflamed intestinal regions and compared with non-IBD controls.15-17
Moreover, increased serum TL1A levels were reported in both CD and UC patients with 
active disease compared with controls.17,18
Transgenic mice overexpressing TL1A in a cell specific manner have further elucidated the 
role of TL1A in intestinal inflammation. These mice constitutively express TL1A in T cells 
under the control of the CD2 promoter, in dendritic cells under the control of the CD11c 
promoter, and on myeloid cells under the control of the CSF-1R promoter (c-fms).19-21 In all 
of these models the mice spontaneously develop mild intestinal inflammation that appears to 
be dependent on IL-13 and has a fibrotic component to it. Consistent with a pro-fibrotic role 
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for TL1A, it has been recently shown that DR3-signaling on intestinal myofibroblasts leads 
to increased collagen and IL31RA expression.22 Finally, in vivo mouse models have 
highlighted the exciting promise of TL1A blockade as a therapeutic strategy in IBD. 
Administration of TL1A Ab led to a significant lowering of disease activity index (DAI) as 
compared with the isotype antibody in both adaptive T-cell transfer model of colitis and 
chronic-dextran sulphate sodium, (DSS) model of colitis.22 Furthermore, the treatment with 
TL1A Ab reversed colonic fibrosis back to the original pre-inflamed levels in both models.22
Taken together, these observations suggest that TL1A may be a promising therapeutic target 
for IBD. PF-06480605, a fully human neutralizing monoclonal antibody against TL1A, is 
being used to further explore this potential in IBD treatment. 
Study B7541002 was a Phase 2a study to assess the efficacy of PF-06480605 in participants 
with moderate to severe active UC. The study showed statistically significant results in the 
primary endpoint with an endoscopic improvement (a Mayo endoscopic subscore of 0 or 1 at 
Week 14) rate of 38.2% (95% CI:23.8%-53.7%). Based on this and other additional efficacy 
metrics, PF-06480605 is now being examined in a subsequent Phase 2b study in participants 
with moderate to severe active UC. 
2.2.1. Clinical Overview
PF-06480605 has been explored in a Phase 1 study in healthy participants (Study B7541001) 
and a Phase 2a (Study B7541002) with participants diagnosed with moderate to severe active
ulcerative colitis.  PF-06480605 or placebo has been administered to a total of 
142 participants, 92 healthy volunteers (60 participants in single ascending dose SAD and 
32 participants in the multiple ascending dose MAD periods) by subcutaneous and 
intravenous routes. In study B7541002, 50 participants with moderate to severe ulcerative 
colitis were treated with intravenous, (IV) PF-06480605 administered every 2 weeks. 
2.2.1.1. Clinical Safety 
In the B7541001 study the primary objectives of this study were to evaluate the safety and
tolerability of escalating single intravenous doses and multiple subcutaneous and intravenous 
doses of PF-06480605 administered to healthy participants.
A total of 92 healthy participants, 60 and 32 participants in the SAD and MAD periods, 
respectively, were assigned to and received investigational product (PF-06480605 or 
placebo).  Single doses up to 800 mg and multiple doses up to 500 mg (3 doses every 
2 weeks) were administered. 
There were no deaths, SAEs, severe adverse events, (AEs), AEs resulting from anti-drug 
antibodies or neutralizing antibodies (ADA/NAbs), or participants with dose reductions or 
temporary discontinuations due to AEs during the first in human, (FIH) study with 
PF-06480605.  Additionally, there were no clinically significant abnormalities in laboratory
assessments abnormalities, vital signs, or electrocardiograms, (ECGs).  
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No significant clinical findings have emerged from the completed Phase 1 FIH study or the 
completed Phase 2a study that would impact participant safety. There were no 
immunogenicity associated safety signals, thus, standard safety monitoring (ie, clinical 
evaluation, clinical laboratory tests, cardiac parameters, and testing for ADA) will be 
included in subsequent studies.
2.2.1.2. Clinical Pharmacokinetics 
2.2.1.2.1. Study B7541001
Following single IV infusion dosing, PF-06480605 exposure based on mean area under the
curve (AUCinf) trended toward a greater than dose proportional increase with increasing 
doses across the 1-mg to 800-mg dose range, while the maximum observed concentration 
(Cmax) appeared to increase in approximately dose proportional manner. The mean terminal 
half-life (t½) values ranged between 6 and 23 days. Mean clearance (CL) estimates ranged 
between 0.00688 L/hr and 0.0180 L/hr across all doses. Volume of distribution at steady 
state (Vss) was low with mean values ranging between 3.4 to 5.5 L across all doses, 
indicating that drug is localized mainly to the vascular compartment.
Following multiple SC doses ranging from 30 mg to 300 mg, absorption from the site of 
injection was slow and variable and exposure of Day 1 (as measured by geometric mean area 
under the curve over the dosing interval [AUC] and Cmax) increased in a dose proportional 
manner with an increase in dose, while exposures on Days 15 and 29 trended toward greater 
than dose proportional increases across the 30-mg and 300-mg SC doses.  Estimated 
bioavailability (F) values based on geometric mean AUCτ for the 30 mg, 100 mg, and 
300 mg SC doses on Day 1 were 47%, 44%, and 42%, respectively, relative to the 
corresponding IV doses (AUC 14 days) from the SAD portion of the study. No unexpected 
accumulation occurred based on the accumulation ratios (Rac). Mean t1/2 values for the SC 
doses on Day 29 ranged between 8.7 and 21 days.
Following multiple dose administration of a 500 mg IV dose once every 2 weeks for a total
of 3 doses, higher geometric mean AUCτ values were observed on Days 15 and 29 compared 
to Day 1 with similar Cmax values observed across all dosing days. Mean t1/2 was 20 days.  
2.2.1.2.2. Study B7541002
Following multiple dose IV administration of 500 mg PF-06480605 Q2W for a total of 
7 doses in participants with moderate to severe UC, Cmax values ranged between 99300 and 
1240000 ng/mL across all participants dosed, with a geometric mean of 263400 ng/mL.  
After the attainment of Cmax, PF-06480605 serum concentration exhibited a biphasic decline 
over time, with mean t½ of 19.3 days. Geometric mean area under the concentration-time 
profile from time 0 to time (), the dosing interval (AUC) of 14 days (336 hours) was 
57610000 ng•hr/mL and geometric mean peak-to-trough ratio at steady state (PTR) was
3.0. The geometric mean CL value was 0.00868 L/hr. Volume of distribution at steady state 
(Vss) was low (geometric mean value = 4.69 L), indicating that PF-06480605 was primarily 
distributed in the plasma volume.
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2.3. Benefit/Risk Assessment
2.3.1. Overall Risk-Benefit Assessment for Study
Despite the expanding number of available medical therapies, a significant number of UC 
patients are unable to achieve or maintain remission.  Whereas surgical resection of the colon 
offers definitive treatment, the long-term complications make this a therapy of last-resort.  
Taken together, development of novel medical medicines still remains a critical unmet need 
for UC patients. 
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2.3.2. Potential Benefits
The Phase 2 study assessed the efficacy of PF-06480605 500 mg IV every 2 weeks in 
50 participants with moderate to severe active UC. The study showed statistically significant 
results in the primary endpoint with an endoscopic improvement (a Mayo endoscopic 
subscore of 0 or 1 at Week 14) rate of 38.2% (95% confidence interval, (CI):23.8%-53.7%).
This finding suggests that participants in this study could benefit through control of their 
disease. Furthermore, participants may also benefit from learning about their health, as 
confirmed by study tests and assessments.
2.3.3. Potential Risks
A total of 142 participants have been exposed to PF-06480605 or placebo across 2 studies. 
The Phase 1 study was a single ascending, multiple ascending dose study in 92 healthy 
participants. All adverse events were reported as mild or moderate. The most common 
adverse events reported were headache and stomach pain.  
The Phase 2 study assessed the efficacy of PF-06480605 500 mg IV every 2 weeks in 
50 participants with moderate to severe active UC. Eighteen adverse events were reported as 
related to PF-06480605.  Most of these adverse events were mild (12), 5 were moderate and 
1 was severe (hair loss). There were 4 SAEs reported during the study.  Three SAEs were 
related to underlying UC disease activity and were not considered related to the study drug 
by the investigator.  One SAE (hair loss) was considered severe in severity.  The investigator 
felt that this event could not be ruled out as not being related to the study drug.  
Toxicity studies with PF-06480605 in pregnant rabbits demonstrated no observed adverse 
effects in the highest dose tested (500 mg/kg). It is not known whether the study drug can 
affect male fertility or whether PF-06480605 is secreted in human milk.  Because of the 
investigational nature PF-06480605 should not be administered to pregnant women or 
women who are nursing an infant. 
The current PF-06480605 Investigator’s Brochure (dated March 2019) appropriately 
describes the known benefits and risks of PF-06480605.  Safety and efficacy data will 
continue to be closely monitored in all clinical trials, and any new safety concerns will be
promptly reported. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of PF-06480605 may be found in the investigator’s brochure, 
which is the single reference safety document (SRSD) for this study. 
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Endpoints
Estimands
Induction Period: Primary

To evaluate the efficacy of 
PF-06480605 in induction 
of clinical remission at 
Week 14 in participants 
with moderate to severe 
active UC.

Proportion of participants 
achieving clinical remission 
(defined as a Total Mayo Score 
≤2, with no individual subscore
>1) at Week 14.
E1: This estimand is defined as a 
population average treatment 
difference between PF-06480605 and
placebo in the proportion of 
participants who met the binary 
endpoint without discontinuing 
treatment prior to Week 12 Visit
Treatment: PF-06480605, Placebo.
Population: Participants with 
moderate to severe active UC as 
defined by inclusion/exclusion 
criteria Variable: clinical remission at 
Week 14. 
Intercurrent Events: Treatment 
discontinuation prior to Week 12 
Visit. If a study participant 
discontinued the treatment prior to 
Week 1 Visit but didn’t attend the 
early withdrawal visit, the participant 
will be considered as a non-responder 
for the binary remission endpoint at 
Week 14 for the primary analysis
unless reason for missed visit was 
due to COVID-19.
Population level summary: treatment 
difference between PF-06480605 and
placebo in proportions of responders 
using the binary endpoint.

To evaluate the safety and 
tolerability of 
PF-06480605 during the 
induction period (from 
baseline to Week 14) in 
participants with moderate 
to severe active UC.

Incidence and severity of 
treatment emergent adverse 
events (TEAEs) during the 
induction period.

Incidence of serious adverse 
events (SAEs) during the 
induction period.

Incidence of AEs or SAEs 
leading to discontinuation 
during the induction period.

Incidence of clinically 
significant abnormalities in vital 
signs, ECGs and laboratory 
values during the induction 
period.
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
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Induction Period: Secondary

To evaluate the efficacy of 
PF-06480605 in inducing 
remission at Week 14 in 
participants with moderate 
to severe active UC.

Proportion of participants 
achieving remission (FDA 
definition 1 - defined as 
endoscopic subscore = 0 or 1, 
stool frequency subscore = 0, 
and rectal bleeding subscore = 
0) at Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

Proportion of participants 
achieving remission (FDA 
definition 2 - defined as 
endoscopic subscore = 0 or 1, 
≥1-point decrease from baseline 
to achieve a stool frequency 
subscore = 0 or 1, and rectal 
bleeding subscore = 0) at 
Week 14. 
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

To evaluate the efficacy of 
PF-06480605 on 
endoscopic appearance at 
Week 14 in participants 
with moderate to severe 
active UC during the 
induction period.

Proportion of participants 
achieving endoscopic 
improvement (defined as 
endoscopic subscore = 0 or 1) at
Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

Proportion of participants 
achieving endoscopic remission 
(defined as endoscopic 
subscore = 0) at Week 14.
This composite estimand is defined 
the same as the Estimand E1 except 
the definition of the binary endpoint.

To characterize the PK of 
PF-06480605 in 
participants with moderate 
to severe active UC during 
the induction period.

PF-06480605 trough 
concentrations during the 
induction period through 
Week 14.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To evaluate disease and 
pathway related 
biomarkers (ie, hsCRP 
and fecal calprotectin and 
serum sTL1A) during the 
induction period.

Change from screening in fecal 
calprotectin during the induction 
period through Week 14. 

Change from baseline in hsCRP 
during the induction period 
through Week 14.

Change from baseline in serum 
sTL1A during the induction 
period through Week 14.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
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
To characterize the 
immunogenicity of 
PF-06480605 in 
participants with moderate 
to severe active UC during 
the induction period.

Incidence of development of 
anti-drug antibodies (ADAs) 
and neutralizing antibodies 
(NAbs) during the induction 
period through Week 14.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
Chronic Therapy Period - Primary

To evaluate the safety and 
tolerability of 
PF-06480605 during the 
chronic therapy period 
(from Week 14 to the End 
of Study Visit) in 
participants with moderate 
to severe active UC during 
the chronic therapy 
period.

Incidence and severity of 
treatment emergent adverse 
events (TEAEs) during the 
chronic therapy period.

Incidence of serious adverse 
events (SAEs) during the 
chronic therapy period.

Incidence of AEs or SAEs 
leading to discontinuation 
during the chronic therapy 
period.

Incidence of clinically 
significant abnormalities in vital 
signs, ECGs and laboratory 
values during the chronic 
therapy period.
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
Chronic Therapy Period – Secondary

To evaluate the efficacy of 
chronic therapy of 
PF-06480605.

Proportion of participants 
achieving clinical remission 
(defined as a Total Mayo Score 
2, with no individual subscore
>1) at Week 56.
E2: This estimand is defined as a 
population average treatment 
difference between PF-06480605 and 
placebo in the proportion of 
participants who met the binary 
endpoint without discontinuing 
treatment prior to Week 52 Visit.
Treatment: PF-06480605, Placebo.
Population: Participants with 
moderate to severe active UC as 
defined by inclusion/exclusion 
criteria, and participants who met the 
binary endpoint at Week 14 but did 
not continue to the chronic therapy 
period will be excluded. 
Variable: Clinical Remission at 
Week 56. 
Intercurrent Events: Treatment 
discontinuation prior to Week 52 
Visit. If a study participant 
discontinued the treatment prior to 
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Week 52 Visit but didn’t attend the 
early withdrawal visit, the participant 
will be considered as a non-responder 
for the binary remission endpoint at 
Week 56 for the secondary analysis
unless reason for missed visit was 
due to COVID-19.
Population level summary: treatment 
difference between PF-06480605 and
placebo in proportions of responders 
using the binary endpoint.

Proportion of participants 
achieving sustained clinical 
remission (ie, clinical remission 
at both Week 14 and Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is sustained 
clinical remission.

Proportion of participants 
achieving remission (FDA 
definition 1 - defined as 
endoscopic subscore = 0 or 1, 
stool frequency subscore = 0, 
and rectal bleeding subscore = 
0) at Week 56.

Proportion of participants 
achieving sustained 
remission-FDA definition 1
(ie, remission-FDA definition 1
at both Week 14 and Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is remission 
(FDA definition 1) at Week 56 or 
sustained remission (FDA 
definition 1).

Proportion of participants 
achieving remission (FDA 
definition 2 - defined as 
endoscopic subscore = 0 or 1, 
≥1-point decrease from baseline 
to achieve a stool frequency 
subscore = 0 or 1, and rectal 
bleeding subscore = 0) at 
Week 56.

Proportion of participants 
achieving sustained 
remission-FDA definition 2 
(ie, remission-FDA definition 2 
at both Week 14 and Week 56).  
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is remission 
(FDA definition 2) at Week 56 or 
sustained remission (FDA 
definition 2).

Proportion of participants 
achieving endoscopic 
improvement (defined as 
endoscopic subscore = 0 or 1) at 
Week 56.

Proportion of participants 
achieving sustained endoscopic
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is endoscopic 
improvement at Week 56 or sustained 
endoscopic improvement.
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improvement (ie, endoscopic
improvement at both Week 14 
and Week 56).

Proportion of participants 
achieving endoscopic remission 
(defined as endoscopic 
sub-score = 0) at Week 56.

Proportion of participants 
achieving sustained endoscopic
remission (ie, endoscopic
remission at both Week 14 and 
Week 56).
This composite estimand is defined 
the same as the Estimand E2 except 
that the binary endpoint is endoscopic 
remission at Week 56 or sustained 
endoscopic remission. 

To characterize the PK of 
PF-06480605 in 
participants with moderate 
to severe active UC during 
the chronic therapy 
period.

PF-06480605 concentration 
from Week 14 through the End 
of Study Visit.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To evaluate disease and 
pathway related 
biomarkers (ie, hsCRP 
and fecal calprotectin and 
serum sTL1A during the 
chronic therapy period.

Change from Week 14 in fecal 
calprotectin during the chronic 
therapy period through the End 
of Study Visit. 

Change from Week 14 in hsCRP 
during the chronic therapy
period through the End of Study 
Visit.

Change from week 14 in serum 
sTL1A during the chronic 
therapy period through the End 
of Study Visit.

Change from baseline through 
the End of Study Visit in fecal 
calprotectin.

Change from baseline through 
the End of Study Visit in 
hsCRP.

Change from baseline through 
the End of Study Visit in serum 
sTL1A.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.

To characterize the 
immunogenicity of 
PF-06480605 in 
participants with moderate 
to severe active UC during 

Incidence of development of 
anti-drug antibodies (ADAs) 
and neutralizing antibodies 
(NAbs) from Week 14 through 
the End of Study Visit.
There is no defined estimand for 
these endpoints and they will be 
analyzed descriptively. Missing data 
will not be included in the analysis.
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4. STUDY DESIGN
4.1. Overall Design
This is a Phase 2b, multi-center, randomized, double-blind, placebo controlled, parallel group
study design, to assess the efficacy, safety and pharmacokinetics of PF-06480605 in 
participants with moderate to severe active UC. Approximately 240 participants will be 
randomized, and 216 of them are expected to complete the induction period, assuming a 
10% drop out rate.  Participants will be randomly assigned to 1 of 9 treatment sequences 
using an allocation ratio of 
.  The numbers of planned participants for the 
9 treatment sequences (A-I) are listed in Table 2.  Randomization will be stratified according 
to whether or not the participants have prior exposure to anti-TNFs in order to achieve a 
balanced proportion of participants with prior exposure to anti-TNFs across different 
treatment sequences.
This study will occur over 4 periods; screening, induction, chronic therapy, and follow-up.  
The first screening period may last up to 6 weeks to assess eligibility and may occur over a 
few study visits. During the screening period, eligibility will be assessed by review of the 
medical history, current/prior medications, and a colonoscopy/sigmoidoscopy to confirm 
moderate to severe active UC disease. (Please see the SoA for all assessments). The
induction part of the study will be 12 weeks in duration, and all participants will be assigned 
to a treatment regimen. At the beginning of this period (baseline visit, or Day 1), participants
will be randomly assigned to 1 of 9 treatment sequences (Table 2) according to a predefined 
randomization schedule. During the 12-week induction period, participants will receive 
50 mg, 150 mg, 450 mg, or matched placebo. Participants will receive blinded induction 
treatment administered SC once every 4 weeks at their scheduled study visit according to the 
assigned treatment sequence. During this time participants will also collect UC symptoms 
(Partial Mayo Score) on a
eDiary.  Other assessments will be completed at the 
scheduled visits such as safety labs, PK collection, and the completion of UC scales by the 
participants. Once the induction treatment is completed (Week 12), all participants will have 
a colonoscopy or sigmoidoscopy at Week 14.  At Week 16, dosing will resume for all 
participants.  During the chronic therapy period all participants will be on active drug, 
(50 mg, 150 mg, or 450 mg administered SC every 4 weeks). Treatment will continue 
through Week 52. Participants will continue to collect 
UC symptoms on the eDiary, as 
well as report for scheduled study visits every 4 weeks, where safety labs PK, and UC scales 
will be completed by the participants. All participants will return for Week 56 so that the 
final colonoscopy or sigmoidoscopy is completed. The last 2 scheduled visits are a part of 
the follow-up portion of the study where safety assessments are collected, and many of the 
prohibited treatments are now permitted. The final follow-up period will be 12 weeks in 
duration.  The
UC symptoms will continue to be collected until the end of the study.  
Overall the study participation for each participant is approximately up to 70 weeks. Please 
see Section 1 for the study design schema. 
Participants that discontinue at any time during the study will proceed into the follow-up 
period with an early withdrawal visit (see Section 7.1).
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Table 2.
Treatment Sequence
Treatment 
Sequence
Treatment Sequence Description
Induction Period
Chronic Therapy Period
A
PF-06480605 450 mg SC Q4W
PF-06480605 450 mg SC Q4W
B
PF-06480605 450 mg SC Q4W
PF-06480605 150 mg SC Q4W
C
PF-06480605 450 mg SC Q4W
PF-06480605 50 mg SC Q4W
D
PF-06480605 150 mg SC Q4W
PF-06480605 150 mg SC Q4W
E
PF-06480605 150 mg SC Q4W
PF-06480605 50 mg SC Q4W
F
PF-06480605 50 mg SC Q4W
PF-06480605 50 mg SC Q4W
G
Placebo SC Q4W
PF-06480605 450 mg SC Q4W
H
Placebo SC Q4W
PF-06480605 150 mg SC Q4W
I
Placebo SC Q4W
PF-06480605 50 mg SC Q4W
4.2. Scientific Rationale for Study Design
Study B7541002, a Phase 2A, Multicenter, Single Arm, Open-Label, Two-Stage, Study to 
Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of PF-06480605 in 
Participants with Moderate to Severe Ulcerative Colitis has demonstrated PF-06480605 to be 
safe, well-tolerated, and efficacious following administration of 500 mg IV every 2 weeks 
(Q2W) for 12 weeks.
The induction period will inform Phase 3 dose selection. Subcutaneous administration every 
4 weeks (Q4W) was considered for this study since it is the intended route of administration 
and the population PK/PD model-predicted P90 (proportion of subjects maintaining minimum 
target coverage ≥90%) values of 
for the 450 mg Q4W SC (highest dose to be 
evaluated in this study) and the efficacious 500 mg Q2W IV doses, respectively, supports 
both the route of administration and frequency of dosing.
The chronic therapy period will enable the characterization of long-term immunogenicity.
Given the high immunogenicity observed in healthy volunteers (Study B7541001) and 
participants with Ulcerative Colitis (Study B7541002), capturing the trough at each PK visit 
 is required to evaluate the impact of immunogenicity on drug concentration 
over the course of the study. 
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In the definitive embryo-fetal development, (EFD) study, PF-06480605 was intravenously 
administered by bolus injection to pregnant New Zealand White female rabbits once daily on 
Gestation Days (GD) 7 and 14 at 0, 60, 180, or 500 mg/kg/dose. The maternal and 
developmental no-observed-adverse-effect level (NOAEL) for PF-06480605 in rabbits was 
the highest dose tested, 500 mg/kg/dose, based on a lack of test article-related effects. Also, 
there were no findings in male or female reproductive organs in the 3- or 6-month toxicity 
studies in mice and cynomolgus monkeys, respectively. It is not known whether 
PF-06480605 can affect male fertility or whether PF-06480605 is secreted in human milk. 
Because of the investigational nature of this product, PF-06480605 should not be
administered to pregnant women or women who are nursing an infant. Giving the unlikely 
risk of human teratogenicity/fetal toxicity all acceptable effective methods of contraception 
will be required for approximately 5 half -lives (3 months), following the last dose of IP. 
(See Appendix 4). The potential risk of exposure to PF-06480605 in a sexual partner of a 
male participant in this study via ejaculate is low, and therefore no contraception (condom) 
use in male participants is warranted. The calculated safety margin of 34,852 is >100-fold
between the estimated partner exposure due to seminal transfer and the NOAEL for serious 
manifestations of developmental toxicity in nonclinical studies.  The safety margin of 
100-fold is based on applying a 10-fold safety factor for interspecies extrapolation and a 
10-fold safety factor for susceptible populations.23
Banked biospecimens will be collected for exploratory 
and retained in the Biospecimen Banking 
System (BBS), which makes it possible to better understand the investigational product’s 
mechanism of action and to seek explanations for differences in, for example, exposure, 
tolerability, safety, and/or efficacy not anticipated prior to the beginning of the study.
4.3. Justification for Dose
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4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including; screening, induction phase, chronic therapy period, and the follow-up 
portion of the study up through and including visit (Visit 18), approximately 12 weeks post 
last dose of IP.  The end of the study is defined as the date of the last visit (Visit 18), by the 
last participant across all sites globally.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants 18 years, or (the minimum country specific age of 
consent if >18) to 75 years of age at the time of informed consent signing.  

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. A diagnosis of UC for ≥3 months. Endoscopy and pathology reports supporting the 
diagnosis, disease duration, and extent of disease (eg, proctosigmoiditis, left-sided 
colitis, or pancolitis) must be available in the source documentation.
3. Participants with moderate to severe active UC as defined by a Total Mayo Score of 
≥6, and an endoscopic subscore of ≥2.  See Section 8 for details. 
4. Active disease beyond the rectum (>15 cm of active disease from the anal verge at the 
screening endoscopy).
5. Participants must have failed or be intolerant (discontinued the medication due to an 
adverse event as determined by the investigator) of at least 1 of the following 
treatments for UC:

Steroids;

Immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or 
methotrexate [MTX]);

Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab);

Anti-integrin inhibitors (eg, vedolizumab);

Anti-IL-12/23 inhibitors (eg, ustekinumab);

JAK inhibitors (eg, tofacitinib).
Please note: Participants currently receiving treatments for UC are eligible providing 
they have been and are anticipated to be on stable dose for the duration of the study. 
(See Appendix 9) for details.
6. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
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Informed Consent: 
7. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent document (ICD) and in this protocol. 
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Participants with a diagnosis of ischemic colitis, infectious colitis, radiation colitis, 
microscopic colitis, indeterminate colitis, or findings suggestive of Crohn’s disease
(eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
2. Participants displaying clinical signs of fulminant colitis or toxic megacolon.
3. Participants with an imminent need for surgery or with elective surgery scheduled to 
occur during the study.
4. Participants with evidence of colonic dysplasia, adenomas, or neoplasia per local 
guidelines.
5. Participants who meet either of the 2 criteria below are considered at risk for colonic 
dysplasia, adenomas, or neoplasia and must have a colonoscopy prior to 
randomization:
a.
If the participant has had extensive (ie greater than left sided) colitis for 8 years 
or disease limited to left side of colon (ie distal to splenic flexure) for 10 years, 
regardless of age, a colonoscopy within 1 year of screening visit is required to 
survey for dysplasia.
b. If the participant is 50 years of age, a colonoscopy within 10 years of screening 
is required to exclude adenomatous polyps.  Participants with adenomatous 
polyps identified on screening endoscopy will be eligible after complete 
polypectomy and follow-up surveillance per local guidelines is negative.
The colonoscopy and pathology reports (if biopsies obtained) must be available in 
the source documentation.
6. Clinically significant infections within 6 months of baseline (eg those requiring 
hospitalization or parenteral antimicrobial therapy, or opportunistic infections), or a 
history of any infection otherwise judged by the investigator to have the potential for 
exacerbation by participation in the study.
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7. Cancer or history of cancer or lymphoproliferative disease within 5 years of baseline 
(with the exception of participants with adequately treated or excised non-metastatic 
basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ).
8. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or or laboratory abnormality that 
t may increase the risk associated with study participation or may interfere with the 
interpretation of study results, and, in the judgment of the investigator, would make 
the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
9. See Section 6.5 and Appendix 8 for details regarding prohibited prior/concomitant 
medications.
10. Known exposure to anti-TL1A (PF-06480605) or any type of anti-TL1A therapy.
Prior/Concurrent Clinical Study Experience:
11. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of investigational 
product used in this study (whichever is longer). Note: local regulations or other 
factors may require more than 30 days.
Diagnostic Assessments:
12. A 12-lead electrocardiogram (ECG) that demonstrates clinically relevant
abnormalities that may affect participant safety or interpretation of study results 
(eg, baseline corrected QT Fridericia method[QTcF] >450 msec, complete left bundle 
branch block [LBBB], signs of an acute or indeterminate-age myocardial infarction, 
ST-T interval changes suggestive of myocardial ischemia, second- or third-degree 
atrioventricular [AV] block, or serious bradyarrhythmias or tachyarrhythmias).  If 
QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 
2 more times and the average of the 3 QTcF or QRS values should be used to 
determine the participant’s eligibility.  
13. Chest Radiograph or computed tomography scan showing abnormalities: The study 
will accept a Chest x-ray or computed tomography scan of the chest examination 
performed up to 12 weeks prior to screening if available. See Section 8. 
14. Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB 
infection.  Please see Section 8 and Appendix 2.
15. Presence of active enteric infections: Known pathogenic bacterial, parasitic, fungal 
infections, including
Please see Appendix 2. 
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16. Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses, please
see Appendix 2.
17. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat, if deemed necessary:

Hemoglobin 8.0 g/dL or hematocrit 30% (0.30 v/v);

Absolute lymphocyte count (ALC) 0.8 x 109/L (800/mm3);

Absolute neutrophil count (ANC) 1.2 x 109/L (1200/mm3);

Platelet count 100 x 109/L (100,000/mm3);

Aspartate aminotransferase, (AST) or alanine aminotransferase, (ALT) ≥2.0 times 
the upper limit of normal (ULN);

Total bilirubin level ≥1.5 times the ULN; participants with a history of Gilbert’s 
syndrome may have a direct bilirubin measured and would be eligible for this 
study provided the direct bilirubin in ≤ULN;

Screening laboratory tests with abnormal results (if considered by the investigator 
to be transient and inconsistent with the subject’s clinical condition) may be 
repeated within the screening window to confirm abnormal results.  If results 
return to protocol acceptable limits within the screening period, the subject may 
enter the study.
Other Exclusions:
18. History of alcohol or drug abuse (per the investigator’s discretion) that would prevent 
the participant from being compliant with study visits and required procedures.
19. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
Pfizer employees, including their family members, directly involved in the conduct of 
the study.
5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
female participants have selected an appropriate method of contraception from the permitted 
list of contraception methods (see Appendix 4 Section 10.4.4) and will confirm that the 
participant has been instructed in its consistent and correct use.  At time points indicated in 
the schedule of activities (SoA), the investigator or designee will inform the participant of the 
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need to use highly effective contraception consistently and correctly and document the 
conversation and the participant’s affirmation in the participant’s chart (participants need to 
affirm their consistent and correct use of at least 1 of the selected methods of contraception).  
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued or if pregnancy is known or suspected in the 
participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to receive investigational product or entered into the 
study. A minimal set of screen failure information is required to ensure transparent reporting 
of screen failure participants to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse event (SAE).
A participant who qualified for this study but did not enroll within the protocol prescribed 
screening period may be re-screened.  All screening procedures must be repeated, and the 
participant assigned a new 8-digit study-specific participant identification (SSID) number.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the IP is compound PF-06480605 and matching placebo administered SC; and 
will be administered SC once every 4 weeks (Q4W). To maintain the blind, every participant 
will receive
SC injections at all visits where participants are receiving 
investigational administration according to the SoA. 
Table 4.
Study Intervention(s) Administered
Intervention Name
PF-06480605 Solution for Injection, 
100 mg/mL.
Placebo.
ARM Name
Induction, Maintenance.
Induction.
Type
Biologic.
Biologic.
Dose Formulation
Solution for Injection.
Solution for Injection.
Unit Dose Strength(s)
100 mg/mL,
mL extractable 
volume.
Placebo to match,
mL 
extractable.
Dosage Level(s)
50 mg, 150 mg, 450 mg.
Placebo.
Route of Administration
Subcutaneous.
Subcutaneous.
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Investigational Medicinal 
Product (IMP) and 
Noninvestigational Medicinal 
Product (NIMP)
IMP.
IMP.
Sourcing
Provided centrally by the sponsor.
Please reference the Investigational 
Product Manual for details on Drug 
ordering.
Provided centrally by the 
sponsor.
Please reference the 
Investigational Product 
Manual for details on Drug 
ordering.
Packaging and Labeling
Study intervention will be provided in 
vials packaged in individual cartons.  
Each vial and carton will be labeled as 
required per country requirement.
All vials will be provided in cartons 
and both will be labeled in a blinded 
fashion according to local regulatory 
requirements. 
Study intervention will be 
provided in vials packaged in 
individual cartons.  Each vial 
and carton will be labeled as 
required per country 
requirement.
All vials will be provided in 
cartons and both will be 
labeled in a blinded fashion 
according to local regulatory 
requirements.
Current/Former Name(s) or 
Alias(es)]
N/A
N/A
PF-06480605 is a sterile solution for subcutaneous injection. Each vial contains 200 mg of 
PF-06480605 in
mL of solution. PF-06480605 will be provided in dosage strength of 
100 mg/mL in single-use, sterile vials. Placebo for PF-06480605 will also be provided by 
Pfizer as a sterile liquid solution in single-use, sterile vials.
Doses of 50 mg, 150 mg, and 450 mg PF-06480605 or Placebo will be administered through 
4 treatment arms in a 12-week induction phase. After the induction phase, doses of 50 mg, 
150 mg, and 450 mg PF-06480605 will be administered through 3 treatment arms in a 
40-week chronic therapy phase.
PF-06480605 and placebo are supplied in a
mL glass vial and a
mL extractable volume 
with a stopper and aluminum overseal. All vials will be provided in cartons and both will be 
labeled in a blinded fashion according to local regulatory requirements.
6.1.1. Administration
Investigational product withdraw and dilution will be completed by an unblinded pharmacist 
at the investigational site.  Administration to the study participant will be completed by 
blinded site personnel at the investigative site.  All participants will be administered 
SC injections every 4 weeks to maintain the blind.  
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6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention, as 
applicable for temperature-monitored shipments. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperature since previously documented for all 
site storage locations upon return to business.
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records). All study 
interventions will be accounted for using an investigational product accountability 
form/record.
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the Investigational Product Manual, (IP Manual). 
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
6. Study interventions should be stored in their original containers and in accordance 
with the labels. 
7. See the investigational product manual (IP manual), package insert, or equivalent for
storage conditions of the study intervention once reconstituted and diluted.
8. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  It will not be considered a protocol deviation if Pfizer 
approves the use of the study intervention after the temperature excursion. Use of the 
study intervention prior to Pfizer approval will be considered a protocol deviation. 
Specific details regarding the definition of an excursion and information the site 
should report for each excursion will be provided to the site in the IP manual.
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9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
Once eligibility has been confirmed through the screening period process, each participant
will be randomized (See Table 4). The investigational product will be dispensed using an 
interactive response technology, (IRT) drug management system at each visit from Visit 1 to 
Visit 15, with the exception of visit 5, as no drug is dispensed at this visit.  A qualified staff 
member will dispense the investigational product via unique container numbers on the label
provided, in quantities appropriate for the study visit schedule.  
See the IP manual for instructions on how to prepare the investigational product for 
administration.  Investigational product should be prepared and dispensed by an 
appropriately qualified and experienced member of the study staff (eg, physician, nurse, 
physician’s assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as 
allowed by local, state, and institutional guidance.
PF-06480605 and placebo will be prepared by qualified unblinded site personnel according 
to the IP manual.  The investigational product will be administered in a blinded manner to 
participants.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Investigational Product
Allocation of participants to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and 
DU or container number assigned.  The confirmation report must be stored in the site’s files. 
Investigational product will be dispensed at the study visits summarized in the SoA.
Returned investigational product must not be redispensed to the participants.
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The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Blinded study with unblinded site pharmacist/site staff who are dispensing drug: Participants 
will be assigned to receive investigational product according to randomization scheme.  
Investigators will remain blinded to each participant’s assigned investigational product 
throughout the course of the study.  In order to maintain this blind, an otherwise uninvolved 
third party will be responsible for the preparation and dispensing of all investigational 
product and will endeavor to ensure that there are no differences in time taken to dispense or 
visual presentation following randomization.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
investigational product records at the site(s) to verify that randomization/dispensing has been 
done accurately.
6.3.2. Breaking the Blind 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
treatment assignment is warranted. Participant safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s treatment assignment unless this could delay further management of the 
participant. If a participant’s treatment assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind. The date and reason that the blind was broken must 
be recorded in the source documentation and case report form (CRF).
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
All doses of investigational product will be administered by the appropriately designated 
blinded study staff at the investigator site.
6.5. Concomitant Therapy
Any prior history (any time prior to the signing of the ICD with no limitations of time) of 
corticosteroids, immunosuppressives (AZA, 6-MP, and MTX), anti-TNFs, anti-integrins, 
anti- IL-12/23 and JAK inihitors will be recorded on the CRF. Any prior UC medications 
taken during the 30 days prior to screening and biologic therapies within 90 days prior to 
screening must be recorded on the CRF. Medications taken within 42 days before the first 
dose of IP will be documented as prior medications. Please see Appendix 8 and 9.
Medication(s) administered/taken following the first dose of IP will be documented as 
concomitant medication.
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6.5.1. Permitted Medications
Participants will be allowed to use the following medications as detailed below:
1.
2.
3.
4.
All concomitant medication(s) and treatment (s) administered/taken during the study must be 
recorded with indication, daily dose, start and stop dates of administration.  All participants 
will be questioned about concomitant medication at each site visit.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are women of childbearing potential (WOCBP) (See Appendix 4).
6.5.2. Prohibited Medications
See Appendix 8 for details regarding prohibited concomitant medications.  Sites are 
encouraged to contact the sponsor should there be questions as to whether a medication is 
permitted or prohibited.
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6.5.3. Rescue Medication
Rescue medication, defined as anything listed under prohibited medications is not permitted 
per the protocol. Participants are free to 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. 
If a participant requires initiation of a new therapy for ulcerative colitis, or medication that is 
on the prohibited list of medication (Appendix 8) the participant should be withdrawn from 
the study and appropriate treatment should be administered at the discretion of the 
investigator.
6.6. Dose Modification
Not Applicable.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue IP.  Per the 
study estimands, if investigational product is permanently discontinued, the participant will 
remain in the study for follow up. Note that discontinuation of investigational product does 
not represent withdrawal from the study.
If a safety or tolerability concern arises, in particular if not responsive to symptomatic 
management, dosing with double-blinded IP may be stopped in an individual participant at 
investigator discretion.  
Any participant who prematurely withdraws from the treatment period (after being 
randomized and during active study intervention) should be followed for 3 study visits
(one being the Early Withdrawal Visit) for a total of 12 weeks from the last dose of 
interventional product. 

Early Withdrawal Visit (replaces Visit 16, follow-up visit 1) to be performed and 
completed. This includes colonoscopy or sigmoidoscopy.

Visit 17 (follow-up 2) is completed 8 weeks after the last dose of investigational 
product.

Visit 18 (follow-up 3) is completed 12 weeks after the last dose of investigational 
product. This is the End of Study Visit.
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed.
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7.1.1. Criteria for Discontinuation
Discontinuation of IP must occur for a participant meeting any of the following conditions: 

Criteria for a potential Hy’s law case are met (See Appendix 6).

Liver Injury (See Appendix 6).

Intent to become pregnant or pregnancy confirmed by serum beta human chorionic 
gonadotropin (-hCG) testing.  (See Appendix 4).

ECG changes (See Appendix 7).

Progressive/Unstable Disease State where the participant would benefit from 
medication currently prohibited during the treatment period.
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation/withdrawal
visit should be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation/withdrawal visit applies only to participants who are randomized 
and then are prematurely withdrawn from the study.  Participants should be questioned 
regarding their reason for withdrawal. Any participant who prematurely withdraws from the 
treatment period (after being randomized and during active study intervention) should be 
followed for 3 study visits (one being the Early Withdrawal Visit) for a total of 12 weeks 
from the last dose of interventional product.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples, but data already generated from the samples will continue to be available, and may 
be used to protect the integrity of existing analyses. The investigator must document any 
such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) 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.
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When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Clinical Trial (CT) SAE Report.  In addition, following an 
SAE, lack of completion of all or any of the early discontinuation/withdrawal procedures will 
not be viewed as protocol deviations due to reasons of safety of the participant.
Withdrawal of Consent: 
Participants who request to discontinue receipt of study treatment will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of investigational product or also from study 
procedures and/or posttreatment study follow-up, and entered on the appropriate CRF page.  
In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
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8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
8.1. Efficacy Assessments
Efficacy assessments for this study will include Mayo Scores, and endoscopic subscores.  
The following procedures and assessments are required to achieve the scores. 
8.1.1. Colonoscopy/Sigmoidoscopy
A screening endoscopy (ie, colonoscopy or flexible sigmoidoscopy) should be performed 
preferably
 (Day 1) to allow Total Mayo Score calculation.  
The endoscopic subscore, read by the Central Reader must be available at the baseline visit.  
The assessment by the Central Reader will be used to derive the Total Mayo Score for study
eligibility.  The endoscopic report and pathology report must be available in the source 
documents.
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additional inflamed biopsies are collected for histology, then the total biopsy samples 
collected during pre and post treatment endoscopies will be 
During treatment endoscopies, samples should be obtained from approximately the same 
anatomic location as the baseline, pre-treatment biopsy collection. For all biopsies collected, 
record the colonic segment and approximate distance from the anal verge for each sample in 
the source documents. Exploratory biomarkers may be analyzed.
8.1.2. Total Mayo Score
Total Mayo Score will be based on the centrally-read endoscopic subscore, stool frequency, 
rectal bleeding and physician’s global assessment.
The Mayo Score is a tool designed to measure disease activity for UC. The Mayo scoring
system ranges from 0 to 12 points and consists of 4 subscores, each graded 0 to 3 with the
higher score indicating more severe disease activity (See Appendix 10).

Stool frequency (Subscore 0-3).

Rectal bleeding (Subscore 0-3).

Findings on endoscopy (Subscore 0-3).

Physician’s global assessment (Subscore 0-3).
Calculation of the Mayo Score requires an assessment of the participant’s stool frequency 
and any amount of blood in the stool.  The Mayo scores will be calculated based on the 
participant’s stool electronic diary, (e-diary) data recorded over the 
days prior 
to the endoscopy bowel preparation procedure.  Investigator sites will be trained on the 
electronic diary usage and will train participants on use of the e-diary.  Electronic diary data 
entered by the participant will be reviewed by the site at each visit.
For baseline endoscopy and post-baseline endoscopies, if there are missing e-diary data, the
average will be taken from the
days reported within 7 days prior to
the endoscopy preparation.
Note: that if there is 1 day of e-diary data or no e-diary data recorded prior to the baseline
endoscopy preparation, then the patient cannot be randomized into the study.
If there are less than
days reported within the 7 days prior to the study visit, the
average will be taken from the limited available data unless there is no e-diary data reported 
within 7 days. In this case, stool frequency and rectal bleeding subscores will be considered
as missing.
The endoscopic imaging appearance will be read by the Central Reader.
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The physician’s global assessment (PGA) acknowledges the other 3 criteria, the subscores, 
the
record of abdominal discomfort and functional assessment and other observations 
such as physical findings, and the patient’s performance status. It is preferred that the same 
medically qualified clinician performs all such assessments for a given participant
throughout the study.
The Mayo Score must be ≥6 and ≤12 with an endoscopic subscore of at least 2 and meet all 
other eligibility criteria to be randomized into the study.  The duration of the time between 
the Mayo endoscopic subscore assessment and baseline should not exceed approximately 
10 days.
8.1.3. Participant Stool Diary
Participants will use an e-diary to record 
stool counts, and rectal bleeding. This 
information is needed to calculate the partial mayo scores collected during the study. 

E-diary: Questions:







Diary data will be assessed at each study visit from screening until the end of the follow up 
period (Week 64). The information extracted will be used for calculation of Mayo score 
considering the data recorded over the
days prior to each study visit. 
day 
patient e-diary data must be completed and assessed prior to any bowel preparations.  If there 
are missing e-diary data, the average will be taken from the
most recently available days 
reported within 7 days prior to the endoscopy preparation.  If there are less than
available 
days reported within the 7 days prior to the study visit, the average will be taken from the 
limited available data unless there is no e-diary data reported within 7 days.  In this case, 
stool frequency and rectal bleeding subscores will be considered as missing. Note: that if 
there is 1 day of e-diary data or no e-diary data recorded prior to the baseline endoscopy 
preparation, then the patient cannot be randomized into the study.
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In order to encourage consistent e-diary recording, participants should enter e-diary data
continuously throughout the study. Instructions for completing the e-diary will be provided
to participants at screening and reviewed at subsequent visits.
8.1.4. Partial Mayo Score
The partial Mayo Score (Mayo Score without endoscopic subscore, ranging from 0 to 9) will 
be calculated from the participant’s stool diary that is collected 
on the e-diary. The 
score will be reviewed at all scheduled visits, prior to administration of IP. 
8.1.5. UC Medical History (Screening)
A diagnosis of UC for ≥3 months.  A medical report documenting disease duration and extent 
of disease (eg, proctosigmoiditis, left-sided colitis, and pancolitis) based upon prior 
colonoscopy/flexible sigmoidoscopy must be available in source documentation.  A biopsy 
report must be available to confirm the histological diagnosis in the participant’s source 
documentation.  
8.1.6. Medical History (Screening)
Investigators should make all reasonable efforts to obtain an accurate and complete medical
history and history of prior medication use when evaluating whether a participant is eligible 
for the study.  The following will be collected at screening: complete medical history, UC
disease history (including disease duration and prior treatments) and tobacco use history. If 
the status of a participant’s medical history is in doubt or information pertaining to a critical
variable is conflicting, every reasonable step to secure proper documentation of correct
medical status should be attempted.  Documentation of the medical and medication histories
over the protocol defined time periods should be available for sponsor review during the
source data verification process.  Questions about prior medications or eligibility should be
directed to the Sponsor Clinician or Sponsor Medical Monitor.
8.1.7. Prior Medications (Screening)
Any prior history (any time prior to signing the ICD with no limitations of time) of 
corticosteroids, immunosuppressives, (AZA, 6-MP, and MTX) anti-TNFs, anti-integrins, 
anti-IL-12/23 and JAK inhibitors will be recorded on the CRF.
8.1.8. Patient Reported Outcomes
In addition to the 
stool diary, there are 4 patient reported outcomes in this study, that 
will be collected at specific scheduled visits (See the SoA). 
When a participant arrives at 
the site for a scheduled visit, the patient reported outcome, (PRO) should be completed as the 
first assessment or closest to the first assessment as possible, according to the SoA. The site 
must also provide to the participants patient reported outcome assessments in the following 
order,
and prior to any other clinical 
assessments.
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8.1.9. Rater Qualifications
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study.  The minimum qualifications a rater must meet for each study 
rating assessment will be outlined in the Rater Assessment Manual provided to each 
participating site.  The level of experience with the target population (or equivalent), specific 
scale experience (or equivalent), and certification required (if applicable) will be listed and 
used to determine whether a rater is approved for a given assessment.  Proposed raters who 
do not meet specific criteria but who may be qualified based on unique circumstances may be 
individually reviewed by the study clinical team to determine whether or not a waiver may be 
issued.  The rater must become certified to perform selected study assessments before he or 
she can participate in the conduct of the study.  For specifically defined assessments, rater 
training and standardization exercises may be conducted, and written and signed 
documentation will be provided by the site for each rater’s certification.  In return, each site 
will be provided written and signed documentation outlining each rater’s certification for 
specific study assessments.  Recertification may be required at periodic intervals during the 
study.  The raters who administer specific study assessments will be documented in a 
centralized location and all site staff who administer ratings will be verified in the site study 
documentation during the conduct of the study.  Every effort should be made to ensure 
consistency in evaluations’; therefore, the same rater should evaluate the same study 
participants throughout the trial.
8.1.10. Imaging Assessments 
Management of Incidental Findings
An incidental finding is one unknown to the participant that has potential health or 
reproductive importance, which is discovered unexpectedly in the course of a research study 
but is unrelated to the purpose and beyond the aims of the study.

Endoscopy, (Colonoscopy or flexible sigmoidoscopy) images will be reviewed by a 
central review facility.  The purpose of this review is to evaluate images for disease 
activity in the colon. Central image review is not a complete medical review of the 
participant.  If, during the central review process, an unexpected observation is 
identified, and this finding could, in the opinion of the central reviewer, have a 
significant health or reproductive consequence, this finding may be shared with the 
study sponsor for disclosure to the principal investigator (PI).  All follow-up testing 
and final diagnosis will be left to the discretion of the medical professionals at the site 
or those with an existing physician-participant relationship.  The PI will be 
responsible for reporting any AEs identified from incidental findings as described in 
the AE reporting section.  Identification of such incidental findings during the central 
review process should not be expected, and the site maintains responsibility for 
performing a general safety review of all images as per site protocols. 
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8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
8.2.1. Physical Examinations, Height and Weight
Complete and targeted physical examinations are performed as indicated according to the
SoA.  
It is recommended that weight be measured in kilograms (kg) and that height be measured in 
centimeters (cm), however pounds (lbs) and inches may be used, (in).  Height and weight 
will be measured to 1 decimal place.  Height and weight measured without shoes, and 
multiple layers of clothing.
For measuring weight, a scale with appropriate range and resolution should be used and must 
be placed on a stable, flat surface.  (see the SoA).
8.2.1.1. Complete Physical Examinations
Physical examinations may be conducted by a physician, trained physician’s assistant or 
nurse practitioner as acceptable and according to local regulation.  A complete physical 
examination will include, at a minimum, assessments of general appearance; skin, head, eyes,
ears, nose, and throat (HEENT), heart, lungs, breast (optional), abdomen, and external 
genitalia (optional), extremities, neurologic function, back, and lymph nodes.
8.2.1.2. Targeted Physical Examinations
Targeted physical examinations must be performed by a physician, trained physician’s 
assistant or nurse practitioner as acceptable and according to local regulation and should 
include skin, heart, lungs, abdomen and examination of body systems where there are 
symptom complaints by the participant. 
8.2.2. Vital Signs
Vital Signs will be measured with the participant in a sitting position after 5 minutes of rest 
and will include temperature, (oral tympanic, or axillary C°or F°) systolic blood pressure, 
(BP), diastolic BP, and pulse rate (PR), and will be measured at the nominal time points 
specified in the SoA per the following specifications:
BP and pulse rate measurements will be assessed with a completely automated device in a 
sitting position.  Manual techniques will be used only if an automated device is not available.  
It is preferred that the same arm (preferably the dominant arm) be used throughout the study.  
Additional collection times, or changes to collection times of BP and PR will be permitted, as 
necessary, to ensure appropriate collection of safety data.
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8.2.3. Chest X-Ray or Chest Computerized Tomography, (CT)(Screening only)
The study will accept a Chest x-ray examination (or chest CT) performed up to 12 weeks
prior to screening if available.  If no previous exam has been completed, a Chest X-ray
(posterior-anterior and lateral views) or a CT scan may be performed at the discretion of the 
investigator however local guidelines should be followed.  There should be no evidence of
tuberculosis (TB), general infections, heart failure or malignancy if taken at screening or 
within the 12 weeks prior to screening and must be read by a qualified radiologist, or an 
expert of lung disease. Documentation of the official reading must be available in the source 
documentation.  
8.2.4. Interferon Gamma Release Assay Tuberculin Test (Screening only)
Participants will be screened for infection with TB using a Interferon Gamma Release Assay 
(IGRA) test. The following are acceptable IGRA assays: QuantiFERON®-TB Gold test 
(QFT-G), QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT® TB test.  Site 
personnel should follow the processing and analyses steps based on the assay chosen.  
Documentation of IGRA product used and the test result must be in the participant’s source 
documentation  
If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result 
is obtained, enrollment may proceed.  A positive test on repeat is exclusionary. 
Participants with repeat indeterminate IGRA results may be enrolled after consultation with 
pulmonary or infectious disease specialist that determines low risk of infection 
(ie, participant would be acceptable for immunosuppressant (eg, anti-TNF) treatment without 
additional action).
Participants adequately treated (in the opinion of the appropriately qualified 
personnel - which may include a pulmonary or infectious disease specialist, or locally 
acceptable expert as defined by local guidelines) for latent and/or active tuberculosis 
infection may be enrolled regardless of IGRA results provided the treatment is well 
documented in the subject’s medical records and/or source documentation prior to enrollment 
in the study.  See Appendix 2.
8.2.5. HIV (Screening only)
All participants will be screened for human immunodeficiency virus, (HIV), tested at the 
site’s local lab, or central lab if necessary. Note: a documented negative HIV test within 
12 months of screening is acceptable and does not need to be repeated. See Appendix 2.
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8.2.6. Hepatitis 
All participants will be tested for Hepatitis B and C. 
Participants must undergo testing for HBV surface antigen (HBsAg), HBV core antibody 
(HBcAb), and HBV surface antibody (HBsAb). This will be performed in CLIA (Clinical 
Laboratory Improvement Amendments) certified laboratory.

Participants who are negative for all three serology tests may be eligible.

Participants who are HBsAg positive will be excluded.

HbsAg negative, HBcAb positive, and HBsAb negative participants are to be 
excluded from the study. 

Participants who are HBsAg negative, HBcAb negative and HBsAb positive may be 
eligible for the study. Partipants enrolling from Japan or other countries that require 
HBV DNA testing, the following is to be implemented:

Participants who are HBsAg negative, HBcAb negative and HBsAb positive and 
provide documentation of prior HBV vaccination, may be eligible for the study 
and will not require HBV DNA. 

Participants who are HBsAg negative, HBcAb negative and HBsAb positive 
without documentation of prior HBV vaccination AND participants who are 
HBsAg negative, HBcAb positive, and HBsAb positive, will have HBV DNA 
assessed at screening.  If HBV DNA is detectable, participants will be excluded.  
If HBV DNA is not detectable, participants may be eligible.  If enrolled, HBV 
DNA will also be assessed at Week 12 and repeated every 12 Weeks and if 
detected during the study, participant will be discontinued from study 
participation.
For hepatitis C, all participants will undergo testing for hepatitis C antibody (HCVAb) during 
Screening. Participants with positive HCVAb tests will be reflex tested for HCV ribonucleic 
acid (hepatitis C virus, (HCV) RNA).  Only participants with negative HCVAb or HCV RNA 
will be allowed to enroll in the study.  See Appendix 2.
Hepatitis testing (HBsAg, HBcAb, HBsAb, HCV Ab, and HCV RNA) will be performed by 
the central laboratory.  HBV DNA testing will be performed locally as per country 
requirement.  Note: if needed, this testing can be done by the central lab. 
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8.2.7. Active Enteric Infections (Positive Stool culture and sensitivity) (Screening only)
All participants will be tested for the presence of known pathogenic bacterial, parasitic, 
fungal infections, including
Participants with clinically significant 
underlying disease will be screen-failed, so as not to predispose participants to infections.  
However, participants may be treated and re-tested or re-screened at the discretion of the 
investigator. See Appendix 2.
8.2.8. Electrocardiograms
12-Lead ECGs should be collected at times specified in the SoA section of this protocol
using an ECG machine that automatically calculates the heart rate and measures PR, QT, and 
QTc intervals and QRS complex. All scheduled ECGs should be performed after the 
participant has rested quietly for at least 10 minutes in a supine position. 

Baseline ECG: 
For the pre-dose, DAY 1 ECG assessment, triplicate 12-lead ECGs will be obtained 
approximately 2-4 minutes apart; the average of the triplicate ECG measurements 
collected pre-dose on Day 1 will serve as each participant’s baseline QTc value. 
If a post dose QTc interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner,
at the discretion of the investigator), or QTc intervals get progressively longer, the participant
should undergo continuous ECG monitoring.  A cardiologist should be consulted if QTc 
intervals do not return to less than the criterion listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time to achieve precise ECG recordings.  If a machine-read QTc value is 
prolonged, as defined above, repeat measurements may not be necessary if a qualified 
medical provider’s interpretation determines that the QTc values are in the acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.9. Injection Site Reactions
Each participant will be monitored for 60 minutes after their first dose of IP. After 
60 minutes the injection site will be monitored for redness, swelling, or any type of 
inflammation and this should be recorded as an injection site reaction, if applicable on the 
appropriate CRF. 
If the participant has a delayed reaction, (after they leave the investigative site) this should 
also be captured as an injection site reaction,  on the adverse event CRF page.  At the next 
dosing visits, (if there were no injection site reactions) the participant may be monitored for 
30 minutes after dosing for the remaining visits per the investigator discretion.
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8.2.10. Contraception Checks
For women of child bearing status, contraception will be discussed at every scheduled visit to 
ensure compliance. 
8.2.11. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency.
Screening laboratory tests with abnormal results (if considered by the investigator to be 
transient and inconsistent with the participant’s clinical condition) may be repeated within 
the screening window to confirm abnormal results. If results return to protocol acceptable 
limits within the screening period, the participant may enter the study.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within the 3 month follow up period after the last dose of study
intervention should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted 
in accordance with the laboratory manual and the SoA.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
8.2.12. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the investigational product.  Pregnancy tests will also be 
done whenever 1 menstrual cycle is missed during the active treatment period (or when 
potential pregnancy is otherwise suspected) and at the end of the study.  Pregnancy tests may 
also be repeated if requested by institutional review boards (IRBs)/ethics committees (ECs) 
or if required by local regulations.  If a urine test cannot be confirmed as negative (eg, an 
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ambiguous result), a serum pregnancy test is required.  In such cases, the participant must be 
excluded if the serum pregnancy result is positive.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving investigational product), through and including 
a minimum of 3 months after the last administration of the investigational product.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant  provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving investigational product), through and including 
Visit 18.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
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reasonably related to the study intervention or study participation, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form immediately and under no circumstance should this 
exceed 24 hours, as indicated in Appendix 3. The investigator will submit any updated SAE 
data to the sponsor within 24 hours of it being available.
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.  
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the 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 participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of Saves) from the sponsor will review 
and then file it along with the investigator’s brochure and will notify the IRB/EC, if 
appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until 3 months after the last dose of investigational product. If the 
participant completes the study up through Visit 18, the IP will be sufficiently washed out of 
the participant as the average half-life of the drug is approximately 20 days.  
If a pregnancy is reported, the investigator should inform the sponsor within [24 hours] of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  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 SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
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8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a participant enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.3.6. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant;

The administration of an incorrect dosage;

The administration of investigational product that has undergone temperature 
excursion from the specified storage range, unless it is determined by the sponsor that 
the investigational product under question is acceptable for use;

The administration of expired investigational product.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.3.7. Lack of Efficacy
Lack of efficacy is reportable to Pfizer Safety only if associated with an SAE.
8.4. Treatment of Overdose
For this study, when IP >450 mg is administered SC, within less than 2 weeks (between 
dosing) will be considered an overdose.
The Sponsor does not recommend specific treatment for an overdose. In the event of an 
overdose, the investigator/treating physician should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities.
3. Obtain a blood sample for pharmacokinetic (PK) analysis as scheduled at the next 
scheduled visit if requested by the medical monitor (determined on a case-by-case 
basis).  
4. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical l, evaluation of the participant.
8.5. Pharmacokinetics 
8.5.1. Serum for Analysis of PF-06480605 
Blood samples (
) to provide approximately 
serum for PK analysis will be 
collected into appropriately labeled tubes at times specified in the SoA.
The actual times may change but the number of samples will remain the same. All efforts 
will be made to obtain the PK samples at the exact nominal time relative to dosing.

Any scheduled pre-dose collection (ie, Ctrough) obtained post dose or not collected, 
will be captured as a protocol deviation even if results are deemed evaluable.
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Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the lab manual. The samples must be processed and shipped as indicated to 
maintain sample integrity.  Any deviations from the processing steps (eg, sample collection 
and processing steps, interim storage or shipping conditions), including any actions taken, 
must be documented and reported to the sponsor.  On a case by case basis, the sponsor may 
make a determination as to whether sample integrity has been compromised. Any deviation 
from the specified sample handling procedure resulting in compromised sample integrity, 
will be considered a protocol deviation.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures (SOPs).
As part of understanding the PK of the IP, samples may be used for further characterization 
and/or evaluation of the bioanalytical method.  These data will be used for internal 
exploratory purposes and will not be included in the clinical report.  Samples collected for 
this purpose will be retained in accordance with local regulations and, if not used within this 
timeframe, will be destroyed.
The shipment address and contact information for the lab will be provided to the investigator 
site prior to initiation of the trial.
8.5.2. Analysis of Anti-PF-06480605 Antibodies and Neutralizing Anti-PF-06480605
Antibodies 
Blood samples (
) to provide
aliquots of approximately 
of serum each for 
ADA and NAb analyses will be collected into appropriately labeled tubes with no 
preservative (no anticoagulant and no serum separator gel may be used) at times specified in 
the SoA.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the lab manual. The samples must be processed and shipped as indicated to 
maintain sample integrity.  Any deviations from the processing steps (eg, sample collection 
and processing steps, interim storage or shipping conditions), including any actions taken, 
must be documented and reported to the sponsor. On a case by case basis, the sponsor may 
make a determination as to whether sample integrity has been compromised. Any deviation 
from the specified sample handling procedure resulting in compromised sample integrity will 
be considered a protocol deviation.
Samples will be analyzed using validated analytical methods in compliance with Pfizer 
SOPs. Samples determined to be positive for ADA may be further characterized for NAb.
As part of understanding the immunogenicity of PF-06480605, samples may be used for 
additional characterization of an observed immunogenicity response and/or evaluation of the 
bioanalytical method.  These data will be used for internal exploratory purposes and will not 
be included in the clinical study report (CSR). Samples collected for this purpose will be 
retained in accordance to local regulations and if not used within this timeframe will be 
destroyed.
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8.5.3. Exploratory Immunogenicity Peripheral Blood Mononuclear Cell (PBMC) 
Samples 
Blood samples (approximately
 will be collected in sodium heparin tubes and will be 
transferred into appropriate labeled and prepared Accuspin tubes for preparation of cells for 
exploratory 
immunogenicity analyses at the times specified in the SoA.
Detailed collection, processing, storage, and shipment instructions are provided in the lab 
manual.
8.5.4. Exploratory Analysis of ADA Epitopes/Affinities
Blood samples (
) to provide approximately 
 serum for exploratory 
immunogenicity characterization will be collected into appropriate labeled plastic silica clot 
activator tubes with no preservative (no anticoagulant and no serum separator gel may be 
used) at the times specified in the SoA.
Detailed collection, processing, storage, and shipment instructions are provided in the lab 
manual.
Samples will be analyzed using an exploratory analytical method.
Samples collected for this purpose will be retained in accordance to local regulations and if 
not used within this timeframe, will be destroyed.
8.6. Pharmacodynamics
Please see (Section 8.8).
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.7.2. Banked Biospecimens for Genetics
Unless prohibited by local regulations or IRB/EC decision, participants will be asked to 
indicate on the consent document whether they will allow their banked biospecimens to also 
be used to design and conduct research in order to gain a further understanding of other 
diseases and to advance science, including development of other medicines for patients.  This 
component of the sampling banking is optional for participants; they may still participate in 
the study even if they do not agree to the additional research on their banked biospecimens.  
The optional additional research does not require the collection of any further samples.
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See Appendix 5 for information regarding genetic research.  Details on processes for 
collection and shipment of these samples can be found in the lab manual.
8.8. Biomarkers
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8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The primary estimand for the primary endpoint of clinical remission at Week 14 will be the 
population average treatment difference between PF-06480605 and placebo in the 
proportion of participants with moderate to severe ulcerative colitis who achieve the binary
remission endpoint without discontinuing treatment prior to the Week 12 Visit. If a study 
participant discontinues treatment prior to Week 12 Visit but did not attend the early study 
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withdrawal visit, then the participant will be considered as a non-responder for the primary 
analysis. 
Specifically, if a study participant experienced any event leading to early withdrawal and did 
not attend the early withdrawal visit or missed the visit for reasons not associated with 
COVID-19, the missing data will be imputed with non–responder for the binary endpoints.
Estimands for other binary endpoints are similarly defined as for the primary endpoint. The 
intercurrent events will be handled in the similar way to the primary estimand (Section 3).
No estimands are defined for PK, biomarkers, immunogenicity, safety endpoints and tertiary 
endpoints. 
Participants who had data missing due to COVID-19 at a specific visit will be removed from 
analysis for that visit (eg, not included into numerator and denominator in the calculation of 
proportion of responders at the visit where the data are missing due to COVID-19).
9.2. Sample Size Determination
 Assuming a placebo remission rate of 6%, at least 80% 
power, a one-sided type-I error =0.05, the true effect of PF-06480605 with a remission rate 
of 28% (ie, a placebo-adjusted effect of 22%) at the highest dose, and a 6:4:3:3 allocation 
ratio in the order of PF-06480605 450 mg, 150 mg, 50 mg, and placebo, a total of 
approximate 216 participants will need to complete the induction period. Assuming an 
approximately 10% dropout rate in the induction period, approximately a total of 
240 participants (ie, ~90 in the 450 mg dose group, ~60 in the 150 mg dose group, ~45 in 
both the 50 mg dose group and the placebo group) will be enrolled in this study. This sample 
size plan will also provide at least 80% power to detect a placebo-adjusted treatment effect of 
16% without multiplicity adjustment for the high dose (450 mg) group. 
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9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Defined Population for 
Analysis
Description
Safety Analysis 
Population
All participants who take at least 1 dose of investigational 
product.  Participants will be analyzed according to the 
product they received.
Evaluable Population
Intention-To-Treat (ITT)
All participants randomly assigned to investigational product
and who take at least 1 dose of investigational product in 
Induction Period.  Participants will be analyzed according to 
the product they were randomized.
Evaluable Population
modified Intention-To-
Treat (mITT)
All participants randomly assigned to investigational product 
and who take at least 1 dose of investigational product in the 
Chronic Period. Participants will be analyzed according to 
the treatment sequence they were randomized.
PK Concentration 
Population
All participants randomly assigned to investigational product 
and who take at least 1 dose of PF-06480605 and in whom at 
least 1 concentration value is reported.
Biomarker Analysis 
Population 
All participants randomly assigned to investigational product 
and who take at least 1 dose of PF-06480605 and in whom at 
least 1 measurement of biomarker of interest is reported.
Immunogenicity 
Analysis Population
All participants randomly assigned to investigational product 
and who take at least 1 dose of PF-06480605 and in whom at 
least 1 post-treatment anti-drug (PF-06480605) antibody 
determination is reported.  
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data.  This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.
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9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The proportions responding and the risk difference between the 
treatment arms and the placebo arm will be analyzed using an 
unconditional exact method: risk differences and corresponding 2 sided 
unconditional exact 90% confidence intervals will be computed using 
the Chan and Zhang24 method. The confidence intervals for one sample 
proportions will be based on Blyth Still Casella. Details will be 
documented in the SAP. If a study participant discontinued treatment 
prior to Week 12 Visit and didn’t attend the early withdrawal visit, the 
participant will be considered as a non-responder for the binary 
remission endpoint at Week 14 for the primary analysis unless reason 
for missed visit was due to COVID-19. 
Secondary

Secondary binary endpoints will be analyzed in the similar way as the 
primary endpoint. Secondary continuous endpoints will be analyzed 
descriptively and/or using longitudinal mixed models. Details will be 
documented in the SAP.
Tertiary

Analysis methods for tertiary will be described in the SAP finalized 
before database lock.
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary

Safety data will be presented in tabular and/or graphical format and 
summarized descriptively, where appropriate. All safety endpoints 
will be listed and summarized according to Pfizer Data Standards.

Categorical outcomes (eg, AEs) will be summarized by participant 
counts and percentages.

Continuous outcome (eg, BP, heart rate, ECG intervals, etc.) will 
be summarized using N, mean, median, standard deviation, etc.

Laboratory data, ECG intervals, and vital signs crossing the 
thresholds of clinical concern will be tabulated according to Pfizer 
Data Standards.
9.4.2.1. Adverse Events
All safety endpoints (including AEs, SAEs, withdrawals due to AEs or SAEs) will be listed 
and summarized according to Pfizer Data Standards. 
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9.4.2.2. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum post dose QTc values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
9.4.3. Other Analyses 
9.4.3.1. Pharmacokinetic Analysis
PK concentrations will be summarized and presented with summary statistics. A population 
PK model may be developed for the purpose of estimating PK parameters. Any population 
PK model developed to characterize the PK data will be reported separately.  Data 
permitting, the relationship between exposure and clinical responses (efficacy and safety) 
during 12 weeks of treatment in participants with moderate to severe active UC may be
explored using either observed or modeled exposures. Any population analyses conducted
will not be part of the clinical study report (CSR) and may be reported separately.
9.4.3.3. PK/PD Unblinding Plan
A PK/PD unblinding plan approved by the clinical lead, clinical pharmacology lead, and 
statistical lead will be in place to describe the procedures to be employed in safeguarding the 
study blind for members of the study team.  These procedures will be in accordance with 
applicable Pfizer standard operating procedures (SOPs) for releasing randomization codes 
and breaking the study blind.  Under this plan a group of statisticians, PK/PD data provider, 
PK/PD analyst and PK/PD support would be unblinded in order to initiate the building of 
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statistical models of the PK, dose/response as well as exposure/response analysis models and 
conduct associated simulations.  The aim of this work would be to facilitate a fuller 
interpretation of the study upon completion (or at appropriate interim milestone if any).  This 
group will not serve on the study team during the period of early unblinding.  The unblinding 
may occur after the last participant has been randomized.  The details of the procedures will 
be described in the PK/PD Unblinding Plan for Modeling and Simulation for 
Study B7541007 which will be finalized prior to the start of the PK/PD unblinding.
9.4.3.4. Immunogenicity Analysis
Overall incidence of development of ADA and of NAb will be reported along with
relationships of incidence with respect to time. Both continuous endpoints and categorical
endpoints (ie, positive and negative) will be reported for the ADA and NAb assays by time
points samples were collected. Data permitting, the impact of ADA and NAb on PK, PD,
safety and efficacy profiles may be explored.
Additional immunogenicity assessments, including ADA epitopes and affinities are 
exploratory in nature and may not be conducted or reported. 
9.5. Interim Analyses
Two interim analyses may be conducted for the study.  Both interim analyses will be 
conducted by an unblinded team independent of the study team and results from these 
analyses may be reviewed by an internal review committee (IRC). No members of the study 
team will be part of the unblinded team or IRC. 
The first analysis will be conducted when 100% of participants have completed or have the 
opportunity to complete the Week 14 Visit. Each SC induction dose group of PF-06480605 
(450 mg, 150 mg and 50 mg) will be compared with the placebo group in the primary 
endpoint of Week 14 remission. Interim analysis results may be used for internal business 
decisions regarding future study planning. 
The second interim analysis may be conducted when all participants have completed or have 
the opportunity to complete the induction period and approximately 100% of them have 
completed or have the opportunity to complete at least 6 months of chronic therapy. Interim 
analysis results may be used for internal decisions regarding future study planning. 
9.5.1. Data Monitoring Committee 
This study will use an internal review committee (IRC). An external data monitoring 
committee will not be utilized.  An IRC charter will be developed to govern the details of any 
IRC operations.
The IRC will be responsible for ongoing monitoring of safety of participants in the study 
according to the IRC charter.  Members of the IRC will be qualified and experienced in 
reviewing and interpreting clinical study data.  The IRC members will be independent of the 
study team, and unblinded to treatment.  Recommendations may be made to alter the current 
study. The recommendations made by the IRC will be forwarded to the appropriate 
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authorized Pfizer personnel for review and final decision. Pfizer will communicate such 
decisions, which may include summaries of aggregate analyses of safety data, to regulatory 
authorities, investigators, as appropriate. Details of the IRC are described in the IRC charter.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, investigator’s brochure (IB), and other relevant 
documents (eg, advertisements) must be reviewed and approved by the sponsor and 
submitted to an IRB/EC by the investigator and reviewed and approved by the IRB/EC 
before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
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A copy of the ICD(s) must be provided to the participant. Participants who are rescreened 
are required to sign a new ICD and will receive a new screening number. 
The ICD will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The investigator or authorized designee will 
explain to each participant the objectives of the exploratory research. Participants will be 
told that they are free to refuse to participate and may withdraw their consent at any time and 
for any reason during the storage period. A separate signature will be required to document a 
participant's agreement to allow any remaining specimens to be used for exploratory 
research. Participants who decline to participate in this optional research will not provide 
this separate signature.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred. All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code. The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs).
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
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Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
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When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from 
source documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the monitoring plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
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Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by 
agreement.
Authorship of publications for the overall study results will be determined by mutual
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the in the study team on demand 
(SToD) system.  
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
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staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory; or as derived 
from calculated values.  These additional tests would not require additional collection of 
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety concerns.
Table 5.
Protocol Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes 
(Abs)
PT/INR/PTT
BUN/urea and creatinine
Glucose 
Calcium
Sodium
Potassium
Chloride
AST, ALT
Total bilirubin
Direct Bilirubina
Alkaline phosphatase
Uric acid
Albumin
Total protein
Creatine Kinase (CK)
CK fractionationb
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte 
esterase
Microscopyc
Urine Pregnancy
Serum or urine 
pregnancy test 
(β-hCG)d
Urine drug screend
FSHe
HBV: HBsAg,HBV
surface antigen, 
HBcAB, HBVcore 
antibody, HBV surface 
antibody, HBsAb,
HBV DNA,
HCV RNA
Hepatitis C antibody, 
HCVAb
HIV
QFT-G or other IGRA
Stool Sample to detect 
enteric pathogens,
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
-hCG = beta-human chorionic gonadotropin; BUN = blood urea nitrogen; FSH = follicle-stimulating 
hormone; IGRA=interferon gamma release assay; qual = qualitative; RBC = red blood cell; 
PT=prothrombin time; PTT=partial prothrombin time; QFT-G=quantiferon gold; WBC = white blood 
cell.
a.
Only if total bilirubin is elevated.
b.
Only if CK is elevated.
c.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
d.
Serum or urine -hCG for female participants of childbearing potential, according to the SoA. 
Urine Drug Screen, please see lab manual for details.
e.
For confirmation of postmenopausal status only in female participants who have been
amenorrheic for at least 12 consecutive months.
Investigators must document their review of each laboratory safety report.
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investigational product under study during pregnancy or breastfeeding, and occupational 
exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding.
Occupational exposure is 
not recorded.
All (and exposure during 
pregnancy [EDP]
supplemental form for 
EDP).
Note: Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.
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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is 100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using an acceptable contraceptive method as described below 
during the intervention period and (for a minimum of 3 months after the last dose of 
investigational product).  The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
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Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 

A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;
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
Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

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).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
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If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, 
regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure.  The 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 and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  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 
preprocedural 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 (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety 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 the investigational product. 
Additional information regarding the EDP may be requested by the sponsor.  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 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  The participant
should return to the investigator site and be evaluated as soon as possible, preferably within 
48 hours from awareness of the abnormal results.  This evaluation should include laboratory 
tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found.  Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT 
abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.8. Appendix 8: Prohibited Concomitant Medications
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10.9. Appendix 9: Permitted Concomitant Medications for UC
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10.15. Appendix 15 Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
10.15.1. Telehealth Visits (if applicable)
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of Activities
or unscheduled visits. Telehealth visits may be used to continue to assess participant safety 
and collect data points. Telehealth includes the exchange of healthcare information and 
services via telecommunication technologies (eg, audio, video, video-conferencing software) 
remotely, allowing the participant and the investigator to communicate on aspects of clinical 
care, including medical advice, reminders, education, and safety monitoring.
The following assessments may be performed during a telehealth visit:

Review and record any AEs and SAEs since the last contact.  Refer to Section 8.3 and 
Appendix 3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method. Confirm that the participant is adhering to 
the contraception method(s) required in the protocol.  Refer to Appendix 4 (if 
applicable).

Patient Reported Outcomes (if applicable).
Study participants must be reminded to promptly notify site staff about any change in 
their health status.
10.15.2. Home Health Visits (If applicable)
A home health care service will be utilized to facilitate scheduled visits per the Schedule of 
Activities.  Home health visits include a healthcare provider conducting an in-person study 
visit at the participant’s location, rather than an in-person study visit at the site. The 
following may be performed during a home health visit:

Lab Collection;

Physical exam;
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
Vital Signs;

ECG; (if applicable).
Germany: alternative practices will be considered and implemented to ensure safety 
monitoring of participants. Sites will not utilize home health visits in accordance with 
Medicinal Products Act of Germany § 4 para.25.
Japan: sites will contact their participants by phone to assess and confirm their safety status. 
If warranted, the investigator will request the participant to visit the site for an emergency 
medical assessment that includes protocol defined assessments, home health visits will not 
occur.  
10.15.3. Laboratory Testing: (If applicable)

If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local 
regulations.  The local laboratory may be a standalone institution or within a hospital. 
The following safety laboratory evaluations may be performed at a local laboratory: 
Please refer to Appendix 2, under Table 5: Protocol Required Safety Laboratory 
Assessments. Not all laboratory collections may be possible.

Hematology;

Chemistry;

Urinalysis;

Viral Surveillance (if applicable);

Pregnancy testing (if applicable); 

PK (if applicable).

If a participant requiring pregnancy testing cannot visit a local laboratory for 
pregnancy testing, a home urine pregnancy testing kit with a sensitivity of at least 
25 IU/mL may be used by the participant to perform the test at home, if compliant 
with local regulatory requirements. The pregnancy test outcome should be 
documented in the participant’s source documents/medical records and relevant data 
recorded on the CRF. Confirm that the participant is adhering to the contraception 
method(s) required in the protocol. 
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
If a local laboratory is used, qualified study site personnel must order, receive, and 
review results. Site staff must collect the local laboratory reference ranges and 
certifications/accreditations for filing at the site.  Laboratory test results are to be 
provided to the site staff as soon as possible.  The local laboratory reports should 

be filed in the participant’s source documents/medical records. Relevant data from 
the local laboratory report should be recorded on the CRF.
10.15.4. Electrocardiograms (If applicable)

If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must 
order, receive, and review results. 
10.15.5. Adverse Events and Serious Adverse Events  

If a participant has COVID-19 during the study, this should be reported as an adverse 
event (AE) or serious adverse events (SAE) and appropriate medical intervention 
provided.  
There are no known drug class effects of anti-TL1A, however it is per the 
investigator’s judgement on whether or not the participant should discontinue study 
invervention. It is recommended that the investigator discuss temporary or permanent 
discontinuation of study intervention with the study medical monitor. 
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10.16. Appendix 16: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
ADA
antidrug antibodies
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ASA
acetylsalicylic  acid
AST
aspartate aminotransferase
AUC
area under the curve
AUCinf
area uder the curve infinity
AUCt
area under the curve over the dosing interval 
AV
atrioventricular
AZA
azathioprine
BBS
Biospecimen Banking System
-hCG
beta-human chorionic gonadotropin
BMI
body mass index
BP
blood pressure
bpm
beats per minute
bSAP
biomarker statistical analysis plan
BSI
back-scattering interferometry
BUN
blood urea nitrogen
C˚
Celsius
CD
Crohn’s disease
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CL
clearance
CLIA
Clincal Laboratory Improvements Amendment
Cmax
maximum observed concentration
cm
centimeter
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
Corona Virus Disease 2019
CPK
creatine phosphokinase
CRA
Cytokine Release Assay
CRF
case report form
CRO
contract research organization
CSF
cerebrospinal fluid
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Abbreviation
Term
CSR
clinical study report
CT
clinical trial
CT
Computed tomography
DAI
disease activity index
DCs
dendritic cells
DcR3
decoy receptor 3
DSS
extran sulphate sodium
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid
DR3
death receptor 3
DU
dispensable unit
E1
Estimands 1
E2
Estimands 2
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
eDiary/e-/Diary
electronic diary
EDP
exposure during pregnancy
EFD
embryo fetal development
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
F
bioavailability
F°
farenheight
FIH
first in human
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GM-CSF
granulocyte-macrophage colony-stimulating factor
GWAS
genome wide association study
HBcAb
hepatitis B core antibody
HBsAb
hepatitis surface antibody
HBsAg 
hepatitis B surface antigen
HBV DNA
hepatitis B deoxyribonucleic acid 
HCVAb
hepatitis C antibody
HCV RNA
hepatitis C ribonucleic acid
HEENT
head, eyes, ears, nose, throat
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
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Abbreviation
Term
hsCRP
high sensitivity C-reactive protein
IB
investigator’s brochure
IBD
inflammatory bowel disease
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IGRA
Interferon Gamma Release Assay
IL
inter-Leuken
ILCs
innate lymphoid cells
IM
intra muscular
IMP
investigational medicinal product
IN
inches
IND
investigational new drug 
INF 
interferon gamma
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ITT
Intention-To-Treat
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous
IWR
interactive Web-based response
JAK
janus kinase inhibitors
kg
kilogram
lbs
pounds
LBBB
left bundle branch block
LFT
liver function test
MAD
Multiple ascending dose
mg
milligram
mITT
modified Intention-To-Treat
MMDAI
Modified Mayo Disease Activity Index
6-MP
mercaptopurine
msec
millisecond
MTX
methotrexate
N/A
not applicable
NAb
neutralizing antibodies
NIMP
noninvestigational medicinal product
NK
natural killer cells
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Abbreviation
Term
NOAEL
no-observed-adverse-effect level
PACL
Protocol administration change letter
PBMC
peripheral blood mononuclear cell
PCD
primary completion date
PD
pharmacodynamic(s)
PGA
Physician Global Assessment
PI
principal investigator
PK
pharmacokinetic(s)
PMDA
Pharmaceutical and Medical Device Agency
PPD
purified protein derivative
PR
pulse rate
PRO
patient reported outcomes
PTR
peak to trough ratio
PT
prothrombin time
PTT
partial thromboplastin time
PVC
premature ventricular contraction/complex
Q2W
every 2 weeks
QFT-GIT
Quantiferon gold TB test in a tube
QFT-G
Quantiferon gold TB test
Q4W
every 4 weeks
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac
accumulation ratios
RBC
red blood cell
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SNPs
single nucleotide polymorphisms
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SSID
study specific participant identification number
SToD
study team on demand
sTL1A
soluable TL1A
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
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Abbreviation
Term
TBili
total bilirubin
TEAE
treatment emergent adverse event
TL1A
TNF-like factor 1A
TNF
tumor necrosis factor
t1/2
terminal half-life
UA
urine analysis
UC
ulcerative colitis
UK
United Kingdom
ULN
upper limit of normal
US
United States
Vss
volume of distribution at steady state
WBC
white blood cell
WOCBP
woman of childbearing potential
WONCBP
woman of non child bearing potential
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