Clinical trial NCT02840721
Conditions: Colitis, Ulcerative
Sponsor: Telavant, Inc.
Start date: 2016-10-26; Completion date: 2018-08-30
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the safety, tolerability, and efficacy of PF-06480605 in subjects with moderate to severe ulcerative colitis.

Detailed description:
This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe ulcerative colitis. Subjects will receive 500 mg of PF-06480605 intravenously every 2 weeks for a total of 7 doses. Blood, stool, and tissue samples will be collected at various time points throughout the study to evaluate safety, tolerability, efficacy, pharmacokinetics, and immunogenicity. Duration of participation for subjects will be approximately 8 months.

Arms: arm 1: PF-06480605 500 mg IV Q2W X 7 doses
Interventions: intervention 1: PF-06480605
Intervention descriptions: intervention 1: PF-06480605 500 mg IV Q2W x 7 Doses

Protocol documents:
Prot_000.pdf: 
PF-06480605
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A PHASE 2A, MULTICENTER, SINGLE ARM, OPEN-LABEL, TWO-STAGE, 
STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND 
PHARMACOKINETICS OF PF-06480605 IN SUBJECTS WITH MODERATE TO 
SEVERE ULCERATIVE COLITIS
Compound:
PF-06480605
Compound Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
129188
European Clinical Trials Database 
(EudraCT) Number:
2016-001158-16
Protocol Number:
B7541002
Phase:
2a
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2
12 Jan 2017

Throughout the protocol, clarified that serum 
total sTL1A (soluble TL1A) will be analyzed. 
Rationale:  To clarify the specific serum TL1A 
test to be performed for this study.

Schedule of Activities: Footnote ‘k’ modified to 
indicate that hepatitis testing (HBsAg, total 
HBcAb, HCVAb confirmed by HCV RNA) 
analysis will be performed by the central 
laboratory.  
Rationale:  To clarify that testing and analysis
for hepatitis will be performed by the central 
laboratory.

Sections 1.2.2, 3.1, 4.1, 4.3, and 7.2.2: Results 
of the preliminary embryo, fetal, and 
developmental (pEFD) toxicity study added and 
applicable protocol text modified accordingly
Rationale:  Addition of non-clinical safety 
information for investigators and regulators. 
Rationale: To correct typographical error and 
clarify the endpoint.

Section 4.1, inclusion criteria #1, removed the 
phrase “or a legally acceptable representative”.  
Rationale:  Adult subjects that lack the capacity 
to consent for the study themselves will not be 
enrolled.

Section 4.1, inclusion criteria #3, increased 
upper age limit of subjects for study inclusion 
from age 65 to age 75. 
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Rationale:  Upper age limit for study 
participation increased to 75 years old to help 
with study recruitment.

Section 4.1 inclusion criteria #4 and 
Section 4.3, notation added that for subjects in 
France, women of childbearing potential 
(WOCBP) are NOT eligible for this study.
Rationale: Country-specific requirement.

Section 4.1, inclusion criteria #8, notation 
added that there is no specific requirement for a 
subject to “washout” of a current treatment and 
that no patient should be actively removed from 
prohibited medications in order to meet study 
inclusion/exclusion criteria, and Section 6.1, 
removed the phrase “(eg, washout of prohibited 
medications)”.  
Rationale:  There is no protocol-required 
washout included in this study.

Section 4.1, inclusion criteria #8, modified 
inclusion criteria for subjects in The 
Netherlands only, indicating that subjects must 
have inadequate response to, loss of response 
to, or intolerance to at least one biological 
therapy, such as an anti-TNF inhibitor.
Rationale:  Revision made to comply with 
country-specific ethics committee requirement.

Sections 4.2, exclusion criteria #10, and 
Sections 6.1 and 7.2.4, clarified that IGRA 
testing to be performed at site’s local laboratory 
where feasible.
Rationale: Sites that are unable to perform 
IGRA at their local laboratory will have IGRA 
testing performed by the central laboratory.

Section 4.2, exclusion criteria #17, modified 
criteria for subjects in France only indicating 
that subjects must not have received any 
biologic treatment for at least 5 half-lives prior 
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to first dose of PF-06480605. (eg, infliximab: 
47.5 days, adalimumab: 70 days, golimumab: 
70 days, vedolizumab: 125 days).
Rationale:  Revision made to comply with 
country-specific requirement.

Section 5.4, added clarification that the end of 
infusion stop time should be recorded when the 
end of infusion saline flush is complete. 
Rationale:  Information provided for clarity.

Section 5.9, added clarification that subjects 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.  Also, if a subject requires initiation of 
a new therapy for ulcerative colitis, the subject 
should be withdrawn from the study and 
appropriate treatment should be administered at 
the discretion of the investigator.  
Rationale:  Information provided for clarity that 
if rescue medication is determined to be 
appropriate for a subject, the subject should be 
withdrawn from the study.

Section 6.2, added suggested order for 
completion of post-dose procedures.  
Rationale:  Information provided for clarity and 
as additional guidance for investigators and site 
personnel. 

Section 7.1, modified the total planned blood 
volume provided by an individual subject who 
completes all scheduled assessments through 
Week 26, per protocol, from approximately 550 
mL to approximately 613 mL.  
Rationale:  Total blood volume changed based 
on recalculation utilizing central vendor blood 
volume requirements.  

Section 7.3.2, sentence added to clarify that for 
all tissue biopsies collected, the colonic 
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segment and approximate distance from the 
anal verge should be notated for each sample in 
the source documents. 
Rationale:  Addition made for clarity.

Appendix 3, addition of appendix to capture 
operational items not included in the mandatory 
contract format for France (ie, French “Contrat 
Unique”). 
Rationale:  France requirement.

Minor administrative changes and sentence 
revisions made throughout the document.  
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.
Amendment 1
18 May 2016

Throughout the protocol, endoscopy 
requirements were modified to remove the 
option that allows flexible sigmoidoscopy.  
Rationale: All subjects will require a 
colonoscopy to assess the entire affected area(s) 
of the colon to enable appropriate efficacy 
assessments in the study.

Throughout the protocol, the requirement for 
subjects to enter their corticosteroid usage via 
e-Diary has been removed, and this information 
will only need to be collected by the site in the 
appropriate CRF, as required for all prior and 
concomitant medication usage.  
Rationale: To eliminate duplication of effort 
and for ease of subject e-Diary requirements, 
there is no need for e-Diary collection of this 
information.

Throughout the protocol, the subject 
observation period following PF-06480605 
administration has been increased to a 
minimum of 2 hours after infusion has ended. 
Rationale: Subject observation period increased 
to 2 hours to monitor subject safety and to 
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provide a consistent and minimum monitoring 
time frame, based on results from the first-in-
human study.

In the schedule of activities and Section 6.2.12, 
clarification made that subjects with AEs as a 
result of positive ADA/NAbs may be requested 
to return for additional follow up for up to 
3 months after the follow up/EOS visit and will 
have PK samples collected in addition to 
ADA/NAb samples. Also added clarification 
that other assessments may also be performed 
during these visits as appropriate depending 
upon the actual AE that is experienced.

Rationale: Additional text added to clarify 
specific requirements during these potential 
additional visits.
In the schedule of activities and Section 6.2.2, 
addition of ADA/NAb and ADA 
epitope/affinity sample collection at Visit 2 
(Week 2, Day 15). 
Rationale: Sample added to collect potential 
early immunogenicity response.

Section 1.3.1:  Statement added that historical 
internal data may be utilized to compare with 
the safety data from this study in order to place 
the safety findings in context given this is a 
single arm study.
Rationale: To provide additional clarity for 
evaluation of safety data.

Section 2.1.2, revised secondary objective to 
reflect that remission will be evaluated at 
Week 14, defined as a total Mayo score of 2 
with no individual subscore >1.  
Rationale: To clearly define how remission will 
be evaluated. 

Section 2.1.2, addition of secondary objective: 
“To evaluate the efficacy of PF-06480605 in 
induction of endoscopic remission at Week 14 
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(defined as Mayo endoscopic subscore of 0) in 
subjects with moderate to severe UC.”  
Rationale: To enable evaluation of endoscopic 
remission.

Sections 2.1 and 2.2, revised primary objective 
and primary endpoint text from “mucosal 
healing” to “endoscopic improvement”, and 
added that endoscopic improvement would be 
defined as Mayo endoscopic subscore of 0 or 1, 
“and without friability”. 
Rationale: Endoscopic improvement can be 
derived from the Mayo endoscopic subscore 
alone, whereas mucosal healing would require a 
validated histologic assessment of the mucosa.
Definition further clarifies evaluation of 
endoscopic improvement.

Section 2.2, addition of secondary endpoint:  
“Remission at Week 14 (defined as a total 
Mayo score 2 with no individual subscore 
>1).”  
Rationale: This will enable comparison with 
legacy data.
 
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
In the protocol summary and Section 3.1, 
individual stopping rules and overall study 
stopping criteria has been added: 1) If 
2 subjects receiving PF-06480605 develop the 
same adverse laboratory event with Common 
Terminology Criteria for Adverse Events
(CTCAE V4.03) Grade 3 or higher, or if 
1 subject develops a laboratory adverse event 
with a CTCAE Grade 4 or higher, then the 
study may be terminated.  2) If 2 subjects
experience an ECG abnormality defined as a 
prolonged QTcF of >500 msec over baseline 
assessment, then the study may be terminated.  
If a single subject experiences a prolonged 
QTcF of >500 msec over baseline assessment, 
then this subject will be discontinued from the 
study.  
Rationale: Individual stopping rules and overall 
study stopping rules added to further evaluate 
safety and feasibility of study continuation
based on emerging data. 

Section 3.1, modified text to indicate that early 
PK readout of PF-06480605 will be conducted 
after at least 6 subjects have completed the 
Week 4 visit to confirm that the predicted 
exposures of PF-06480605 in active UC 
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patients are consistent with expected values, 
based on the healthy subject PK data. Also 
added that following this early PK readout 
analysis, dose may be modified to match the 
exposures observed in healthy volunteers 
receiving 500 mg/kg IV (Study B7541001).  
Rationale: This analysis will now be 
mandatory, rather than optional.

Section 3.4, removed the sentence indicating 
that approximately 40 subjects would be 
enrolled to ensure that 36 evaluable subjects 
complete the study with colonoscopy at 
Week 14.  
Rationale: If futility criteria are not met, 
recruitment will continue until at least 
36 evaluable subjects complete the study with a 
final colonoscopy at Week 14, which is 
required for analysis. 

Section 4.1, inclusion criteria #3 modified to 
delete the phrase “or adult age”.  
Rationale: This phrase was removed to avoid 
enrolling subjects who are younger than 
18 years of age but consider themselves to be 
adults.

Section 4.1 and 4.2, inclusion criteria #4 was 
modified and (former) exclusion criteria #1 was 
removed to clarify that women of childbearing 
potential (WOCBP) will be eligible for the 
study while pEFD toxicology are ongoing 
provided these women use two highly effective 
methods of contraception throughout the study
and until the Week 26 visit (or 98 days after the 
last dose of IP), as outlined in Section 4.3. 
Rationale: WOCBP need not be excluded from 
the study while pEFD toxicology studies are 
ongoing as long as they comply with 
contraception requirements.

Section 4.1, inclusion criteria #8 modified to 
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specify objective criteria to define failure of 
each listed conventional therapy, including dose 
and duration that must have been utilized.  
Rationale: To provide consistent specific 
parameters to define treatment failure.

Section 4.2, exclusion criteria #14 modified to 
add that subjects with current, or a history of 
QT prolongation would be excluded.
Rationale: Clarification made for patient safety.

Section 5.2.1, criteria for interruption or 
stopping infusion related to potential 
immunogenicity related adverse events has 
been added. Additional clarification on specific 
signs and symptoms that may be observed has 
been added.  
Rationale: Infusion reactions are generally not 
well defined and may encompass a wide range 
of clinical events. Appropriate guidance and 
reporting of these events may mitigate risk to 
subjects.

Section 6.1, Section 7.2.1, and Schedule of 
Activities, screening HbA1c added to table of 
laboratory tests.  
Rationale: This test was inadvertently omitted 
from the list previously.

In Section 6.2.1, the requirement for fasting at 
least 8 hours on Day 1 prior to administration of 
PF-06480605 has been removed. 
Rationale: Fasting requirement removed since
there is no data to support this requirement.

In Section 7.3.2, tissue biopsy collections were 
clarified in terms of number and type of tissue 
samples to be collected during the colonoscopy 
procedure. Text related to sample processing 
has been removed from protocol.  
Rationale: To provide clarity and to better 
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specify requirements for appropriate tissue 
sample analysis. Information on sample 
processing will be provided in the central 
laboratory vendor procedure manual. 

In Section 7.3.3, additional information
provided on how Mayo scores will be 
calculated utilizing patient reported diary data 
and handling of missing data.  
Rationale: Additional clarification provided for 
Mayo score calculation and how missing data 
will be managed.

Minor administrative changes and sentence 
revisions made throughout the document.  
Rationale: Revisions made for clarity and to 
correct minor grammatical or spelling errors.
Original protocol
14 March 2016

Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc.
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TABLE OF CONTENTS
APPENDICES .........................................................................................................................17
PROTOCOL SUMMARY.......................................................................................................18
SCHEDULE OF ACTIVITIES................................................................................................23
1. INTRODUCTION ...............................................................................................................27
1.1. Mechanism of Action/Indication.............................................................................27
1.2. Background and Rationale ......................................................................................27
1.2.1. Drug Development Rationale .....................................................................27
1.2.2. Safety Data..................................................................................................28
1.2.2.1. Non-Clinical Safety...................................................................28
1.2.3. Previous Human Experience.......................................................................30
1.2.3.1. Subject Disposition ...................................................................30
1.2.3.2. Pharmacokinetics Results..........................................................31
1.2.3.3. Immunogenicity Results............................................................32
1.2.3.4. Safety Results............................................................................33
1.3. Rationale..................................................................................................................34
1.3.1. Study Rationale...........................................................................................34
1.3.2. Dose Rationale............................................................................................35
1.3.3. Summary of Benefits and Risks .................................................................35
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................36
2.1. Objectives................................................................................................................36
2.1.1. Primary Objectives .....................................................................................36
2.1.2. Secondary Objectives .................................................................................36
2.2. Endpoints.................................................................................................................37
2.2.1. Primary Endpoints ......................................................................................37
2.2.2. Secondary Endpoints ..................................................................................37
3. STUDY DESIGN.................................................................................................................38
3.1. Study Overview.......................................................................................................38
3.2. Duration of Subject Participation............................................................................39
3.3. Approximate Duration of Study..............................................................................39
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3.4. Planned Number of Subjects...................................................................................39
4. SUBJECT SELECTION......................................................................................................39
4.1. Inclusion Criteria.....................................................................................................39
4.2. Exclusion Criteria....................................................................................................42
4.3. Lifestyle Guidelines ................................................................................................46
4.4. Sponsor’s Qualified Medical Personnel..................................................................47
5. STUDY TREATMENTS.....................................................................................................48
5.1. Allocation to Treatment ..........................................................................................48
5.2. Subject Compliance.................................................................................................48
5.2.1. Infusion Discontinuation ............................................................................49
5.3. Investigational Product Supplies.............................................................................50
5.3.1. Dosage Form(s) and Packaging..................................................................50
5.3.2. Preparation and Dispensing........................................................................50
5.4. Administration.........................................................................................................50
5.5. Investigational Product Storage ..............................................................................50
5.6. Investigational Product Accountability...................................................................51
5.6.1. Destruction of Investigational Product Supplies ........................................51
5.7. Prior Medications ....................................................................................................51
5.8. Concomitant Medication(s) and Treatment(s) ........................................................52
5.8.1. Oral Corticosteroids Taken During the Study ............................................52
5.8.2. Permitted Medications................................................................................52
5.8.3. Prohibited Medications...............................................................................52
5.9. Rescue Medication ..................................................................................................53
6. STUDY PROCEDURES .....................................................................................................53
6.1. Screening.................................................................................................................53
6.2. Study Period ............................................................................................................55
6.2.1. Baseline Visit – Week 0/Day 1...................................................................56
6.2.2. Visit 2, Week 2/Day 15 (3 Days Based on Day 1 Visit) ..........................57
6.2.3. Visit 3, Week 4/Day 29 (3 Days Based on Day 1 Visit) ..........................58
6.2.4. Visit 4, Week 6/Day 43 (3 Days Based on Day 1 Visit) ..........................59
6.2.5. Visit 5, Week 8/Day 57 (3 Days Based on Day 1 Visit) ..........................60
6.2.6. Visit 6, Week 10/Day 71 (3 Days Based on Day 1 Visit) ........................61
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6.2.7. Visit 7, Week 12/Day 85 (3 Days Based on Day 1 Visit) ........................62
6.2.8. Visit 8, Week 14/Day 99 (3 Days Based on Day 1 Visit) ........................63
6.2.9. Visit 9, Week 16/Day 113 (7 Days Based on Day 1 Visit) ......................64
6.2.10. Visit 10, Week 20/Day 141 (7 Days Based on Day 1 Visit) ..................65
6.2.11. Visit 11, Week 24/Day 169 (7 Days Based on Day 1 Visit) ..................65
6.2.12. Final On-Site Study Visit: Visit 12, Week 26/Day 183 (7 Days 
Based on Day 1 Visit)......................................................................................66
6.3. Subject Withdrawal.................................................................................................67
7. ASSESSMENTS..................................................................................................................68
7.1. Blood Volume .........................................................................................................69
7.2. Safety.......................................................................................................................69
7.2.1. Laboratory...................................................................................................69
7.2.2. Pregnancy Testing ......................................................................................69
7.2.3. Purified Protein Derivative (PPD) Tuberculin Test....................................70
7.2.4. Interferon Gamma Release Assay Tuberculin Test....................................70
7.2.5. Screening for Clostridium Difficile............................................................70
7.2.6. Vital Signs (Blood Pressure, Pulse Rate, and Temperature) ......................71
7.2.7. Medical History, Physical Examination, Height and Weight.....................71
7.2.8. Electrocardiogram (ECG)...........................................................................71
7.2.9. Chest Radiograph........................................................................................72
7.3. Diagnostic and Efficacy Assessments.....................................................................72
7.3.1. Colonoscopy ...............................................................................................72
7.3.2. Biopsy Collection from Colonic Mucosa ...................................................72
 
7.3.3. Mayo Score.................................................................................................74
7.3.4. Subject Stool Diary.....................................................................................75
7.4. Pharmacodynamics..................................................................................................76
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7.4.2. Serum Soluble TL1A..................................................................................76
7.4.4. High-Sensitivity C-Reactive Protein (hsCRP)............................................76
7.4.5. Fecal Calprotectin.......................................................................................76
7.5. Pharmacokinetics ....................................................................................................77
7.5.1. Serum for Analysis of PF-06480605..........................................................77
7.5.2. Shipment of Serum Samples for Analysis of PF-06480605.......................78
7.6. Immunogenicity ......................................................................................................78
7.6.1. Serum for Analysis of Anti-Drug Antibodies (ADA) and 
Neutralizing Antibodies...................................................................................78
8. ADVERSE EVENT REPORTING......................................................................................81
8.1. Adverse Events........................................................................................................81
8.2. Reporting Period .....................................................................................................81
8.3. Definition of an Adverse Event...............................................................................81
8.4. Medication Errors....................................................................................................82
8.5. Abnormal Test Findings..........................................................................................83
8.6. Serious Adverse Events...........................................................................................83
8.6.1. Protocol-Specified Serious Adverse Events...............................................84
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................84
8.7. Hospitalization ........................................................................................................85
8.8. Severity Assessment................................................................................................86
8.9. Causality Assessment..............................................................................................86
8.10. Exposure During Pregnancy..................................................................................87
8.11. Occupational Exposure .........................................................................................88
8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject 
Withdrawal)...............................................................................................................88
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8.13. Eliciting Adverse Event Information ....................................................................88
8.14. Reporting Requirements........................................................................................88
8.14.1. Serious Adverse Event Reporting Requirements .....................................88
8.14.2. Nonserious Adverse Event Reporting Requirements ...............................89
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................89
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................89
9.1. Statistical Methods ..................................................................................................89
9.2. Sample Size Determination.....................................................................................90
9.3. Efficacy Analysis ....................................................................................................90
9.3.1. Analysis of the Primary Endpoint...............................................................90
9.3.2. Analysis of Secondary Endpoint ................................................................90
9.4. Analysis of Other Endpoints ...................................................................................91
9.4.1. Pharmacokinetic Analysis ..........................................................................91
9.4.2. Immunogenicity Analysis...........................................................................91
9.4.4. Pharmacodynamic Analysis........................................................................92
9.5. Safety Analysis........................................................................................................92
9.5.1. Electrocardiogram Analysis........................................................................92
9.6. Interim Analysis ......................................................................................................92
9.7. Data Monitoring Committee ...................................................................................92
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................93
11. DATA HANDLING AND RECORD KEEPING .............................................................93
11.1. Case Report Forms/Electronic Data Record .........................................................93
11.2. Record Retention...................................................................................................94
12. ETHICS..............................................................................................................................94
12.1. Institutional Review Board/Ethics Committee......................................................94
12.2. Ethical Conduct of the Study ................................................................................94
12.3. Subject Information and Consent..........................................................................95
12.4. Subject Recruitment ..............................................................................................96
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................96
13. DEFINITION OF END OF TRIAL...................................................................................96
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13.1. End of Trial in a Member State.............................................................................96
13.2. End of Trial in All Other Participating Countries.................................................96
14. SPONSOR DISCONTINUATION CRITERIA ................................................................96
15. PUBLICATION OF STUDY RESULTS..........................................................................97
15.1. Communication of Results by Pfizer ....................................................................97
15.2. Publications by Investigators ................................................................................97
16. REFERENCES ..................................................................................................................99
APPENDICES
Appendix 1. Abbreviations....................................................................................................101
Appendix 2. Mayo Scoring System for Assessment of Ulcerative Colitis Activity..............104
Appendix 3. France appendix ................................................................................................105
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PROTOCOL SUMMARY
Background and Rationale:
The investigational product (IP), PF-06480605, is currently being developed for the 
treatment of inflammatory bowel disease (IBD).
PF-06480605 is a fully human neutralizing antibody against Tumor Necrosis Factor-like 
Ligand 1A (TL1A), a member of the tumor necrosis factor (TNF) family of cytokines.  
PF-06480605 contains three mutations in the Fc region to reduce effector function.  Its 
mechanism of action is to neutralize the binding and subsequent signaling of TL1A to its 
functional receptor Death Receptor 3 (DR3).
The TL1A/DR3 pathway has been implicated in the regulation of pathogenic Th1, Th2, Th9
and Th17 T-cells, and of NK and NK-T cell responses, in immune-mediated diseases.  The 
TL1A expression on antigen presenting cells (monocytes, macrophages, dendritic cells) and 
DR3 expression on effector cells (ILC2, T-cells, NK and NK-T cells) is highly dependent on 
pro-inflammatory conditions.  Moreover, data from nonclinical species and humans implicate 
TL1A in the pathophysiology of IBD.1
This multicenter, single arm (non-placebo controlled), two-stage study will be the first use of 
PF-06480605 in subjects with moderate to severe ulcerative colitis (UC).  The objectives of 
this study are to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy (based 
on Mayo endoscopic subscore) of PF-06480605.
The current non-clinical toxicology package available will support a 12 week treatment 
period.  To mitigate the need for a placebo arm, endoscopic improvement, a more objective
endpoint, with lower placebo rates than clinical disease activity scores, was selected as the 
primary endpoint.  All colonoscopies will be read by a Central Reader who will be blinded to 
study treatment.  An induction period (12 weeks of dosing with primary endpoint at 
Week 14) greater than the traditional 8 weeks was chosen to increase the likelihood of 
achieving endoscopic improvement.
Objectives and Endpoints
Primary Objectives

To evaluate the safety and tolerability of PF-06480605 in subjects with moderate to 
severe UC.

To evaluate the efficacy of PF-06480605 in induction of endoscopic improvement (as 
assessed by Mayo endoscopic subscore) at Week 14 in subjects with moderate to 
severe UC.
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Secondary Objectives

To evaluate the efficacy of PF-06480605 in induction of remission at Week 14 
(defined as a total Mayo score 2 with no individual subscore >1) in subjects with 
moderate to severe UC.

To evaluate the efficacy of PF-06480605 in induction of endoscopic remission at 
Week 14 (defined as a Mayo endoscopic subscore of 0) in subjects with moderate to 
severe UC.

To describe the PK of PF-06480605 in subjects with moderate to severe UC.

To evaluate the immunogenicity of PF-06480605 in subjects with moderate to severe 
UC.

To evaluate disease and pathway related biomarkers (ie, high sensitivity C-reactive 
protein [hsCRP] and fecal calprotectin), and serum total soluble TL1A (sTL1A).
Primary Endpoints

Safety and tolerability of PF-06480605: treatment emergent adverse events (TEAEs), 
withdrawal due to adverse events (AEs), and serious adverse events (SAEs) will be 
reported.

Endoscopic improvement at Week 14 (defined as a Mayo endoscopic subscore of 0 
or 1, and without friability).
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Secondary Endpoints

Remission at Week 14 (defined as a total Mayo score 2 with no individual subscore 
>1).

Endoscopic remission at Week 14 (defined as a Mayo endoscopic subscore of 0).

PF-06480605 plasma concentrations.

Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies 
(NAbs). 

Change from baseline in fecal calprotectin.

Change from baseline in hsCRP.

Change from baseline in serum total sTL1A.
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Study Design and Treatments
This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe UC.  
Subjects will receive 500 mg of PF-06480605 intravenously every 2 weeks (Q2W) for a total 
of 7 doses.  At the end of the first stage (12 evaluable subjects with a Week 14 colonoscopy), 
an interim analysis (IA) will be performed for an early efficacy assessment.  Enrollment in 
the second stage will be stopped if the futility criteria are met and any ongoing subjects in the 
second stage will be moved to the follow-up period.  Otherwise, the study will continue to 
enroll additional subjects in the second stage for final efficacy assessment.  
 
The duration of participation for eligible subjects will be approximately 8 months, including 
a screening period of up to 6 weeks, a 12 week treatment period, and a follow-up period 
ending 14 weeks after the last dose of IP.  Subjects with AEs as a result of positive 
ADA/NAbs may be requested to return for additional follow-up for up to 3 months after the 
follow-up/end of study (EOS) visit.  During the treatment period, subjects will visit the site 
every 2 weeks (3 days) for IP administration (7 visits), and then will return to the site every 
4 weeks (7 days) through Week 24 and again at Week 26, for follow-up visits (5 visits).
Stopping Rules
In addition, individual stopping rules will be implemented to further evaluate safety and 
feasibility of study continuation, as described below:  

If 2 subjects receiving PF-06480605 develop the same adverse laboratory event with 
Common Terminology Criteria for Adverse Events (CTCAE V4.03)14 Grade 3 or 
higher, or if 1 subject develops a laboratory adverse event with a CTCAE Grade 4 or 
higher, then the study may be terminated.  
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
If 2 subjects experience an ECG (electrocardiogram) abnormality defined as a 
prolonged QTcF of >500 msec over baseline assessment, then the study may be 
terminated. If a single subject experiences a prolonged QTcF of >500 msec over 
baseline assessment, then this subject will be discontinued from the study.  
Statistical Method
This study employs Simon’s two-stage design, which enables a single arm study with an 
early assessment for futility.  Let p be the proportion of subjects achieving endoscopic 
improvement at Week 14 and the following hypotheses will be tested in this study:
H0: p 6% versus H1: p 41%
In the first stage, it is planned to have 12 evaluable subjects with colonoscopy at Week 14.  If 
no more than 2 subjects have achieved endoscopic improvement AND no subject has 
achieved endoscopic remission, then the study will be stopped for futility; otherwise, the 
study will continue to enroll until approximately 36 evaluable subjects complete the study 
with colonoscopy at Week 14.  If at least 9 subjects achieve endoscopic improvement at 
Week 14 at the end of the second stage, the null hypothesis H0 will be rejected.
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the well-being of the subject.
Screening 
(-42 to -1)
Induction Period
3-Months Follow-Up
Early 
Withdrawala
Treatment Period
3-Months Follow-Up
Final 
Onsite 
Study Visit
Study Visit
Screening 
1
2
3
4
5
6
7
8
9
10
11
12
Study Week
Week -6 to -1
Week 0
Week 2
Week 4
Week 6
Week 8 Week 10 Week 12 Week 14
Week 16
Week 20
Week 24
Week 26
Study Day
Day -42 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 71
Day 85
Day 99
Day 113
Day 141
Day 169
Day 183
Visit Window
N/A
N/A
3 Days based on Day 1 visit
7 Days based on Day 1 visit
Enrollment Procedures
Informed Consent
X
Inclusion/Exclusion 
Criteria
X
X
Demographics & Medical 
historyb
X
Vital Signs
BP and pulse (after sitting 
for 5 minutes)
X
Xb
Xb
Xb
Xb
Xb
Xb
Xb
X
X
X
X
X
X
Temperature (oral, 
tympanic or axiallary) [°C 
or °F])
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight (lbs or kg)d
X
X
X
X
X
X
X
X
X
Height (in or cm)d
X
Medical Procedures
Complete Physical Exame
X
X
X
X
Targeted Physical Exame
X
X
X
X
X
X
X
X
X
X
ECG (12-lead)b
X
X
X
X
X
X
X
X
X
Chest X-rayf
X
Colonoscopy
Colonoscopy f
X
X
X
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Screening 
(-42 to -1)
Induction Period
3-Months Follow-Up
Early 
Withdrawala
Treatment Period
3-Months Follow-Up
Final 
Onsite 
Study Visit
Study Visit
Screening 
1
2
3
4
5
6
7
8
9
10
11
12
Study Week
Week -6 to -1
Week 0
Week 2
Week 4
Week 6
Week 8 Week 10 Week 12 Week 14
Week 16
Week 20
Week 24
Week 26
Study Day
Day -42 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 71
Day 85
Day 99
Day 113
Day 141
Day 169
Day 183
Visit Window
N/A
N/A
3 Days based on Day 1 visit
7 Days based on Day 1 visit
 
 
 
X
X
X
Disease Activity Analysis
X
X
X
X
X
X
X
Total Mayo Score
Xh
Xh
X
Stool Diary Instructions
X
X
X
X
X
X
X
X
X
X
X
X
Stool Diary Data 
(e-diary)i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Stool sample tests for 
enteric pathogens to 
include C. diff toxinsj
X
Serology: HIVk HBsAg, 
total HBcAb, HCVAb 
confirmed by HCV RNAk
X
Tuberculosis test: PPD or 
IGRA per local guidelines 
(assayed at local lab)l
X
Serum Pregnancy Test or 
FSHm
X
Urine Pregnancy Testm
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory: 
Hematology, chemistry, 
UA, PT/PTT/INR
Xn
X
X
X
X
X
X
X
X
X
X
X
X
HbA1c
X
Pharmacodynamics
Retained 
Pharmacogenomic 
Sample (Prep D1)
X
Biomarker hsCRP
X
X
X
X
X
X
X
X
X
X
X
X
X
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Screening 
(-42 to -1)
Induction Period
3-Months Follow-Up
Early 
Withdrawala
Treatment Period
3-Months Follow-Up
Final 
Onsite 
Study Visit
Study Visit
Screening 
1
2
3
4
5
6
7
8
9
10
11
12
Study Week
Week -6 to -1
Week 0
Week 2
Week 4
Week 6
Week 8 Week 10 Week 12 Week 14
Week 16
Week 20
Week 24
Week 26
Study Day
Day -42 to -1
Day 1
Day 15
Day 29
Day 43
Day 57
Day 71
Day 85
Day 99
Day 113
Day 141
Day 169
Day 183
Visit Window
N/A
N/A
3 Days based on Day 1 visit
7 Days based on Day 1 visit
Xo
Xo
Xo
X
X
Serum Total Soluble 
TL1A
Xo
Xo
Xo
Xo
Xo
Xo
Xo
X
X
X
X
X
X
X
Xo
Xo
Xo
X
X
Stool sample for fecal 
calprotectin 
X
X
X
X
X
X
 
 
Xq
X
X
X
X
Pharmacokinetics and Immunogenicity
Pharmacokinetics
Xo
Xo
Xo
Xo
Xo
Xo
Xo
X
X
X
X
Xr
X
ADA and NAb
X
X
X
X
X
X
X
X
Xr
X
X
X
X
X
X
X
X
X
ADA epitope, affinity
X
X
X
X
X
X
X
X
X
X
Trial Treatment Procedureso
Randomization (after all 
screening procedures 
complete and eligibility 
confirmed)
X
Administration of 
PF-06480605
Xs
Xs
Xs
Xs
Xs
Xs
Xs
Dispense Stool Collection 
Kit for Stool Specimen
X
X
X
X
X
Adverse Event 
Monitoring
X











X
Prior and Concomitant 
Medication & Treatments
X












X
Contraception Check
X












X
End of Study CRF
X
Abbreviations:  ADA = anti-drug antibodies; BP = blood pressure; CRF= case report form; ECG = electrocardiogram; EOS = end of study; FSH = follicle stimulating hormone; 
HBA1c = hemoglobin A1c; HBsAg = hepatitis B surface antigen;  total HBcAb = hepatitis B core antibody; HCVAb = hepatitis C antibody; HCV RNA = hepatitis C virus 
ribonucleic acid; HIV = human immunodeficiency virus; hsCRP = high-sensitivity C-reactive protein; PK = pharmacokinetics; PPD = purified protein derivative; PT= 
Promthrombin time; PTT= Partial thromboplastin time; WONCBP = Women of non-childbearing Potential.
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a.
Any subject who prematurely withdraws during active treatment (Week 0 through Week 12) should return for an early withdrawal visit and then enter into 
the follow-up period.
b.
To include smoking history.
c.
At dosing visits, vital signs and ECGs will be collected approximately 30 minutes prior to dosing and 1 hour post-dose.
d.
Height and weight measured without shoes.
e.
Complete physical exam includes review of the following body systems: general appearance, skin, HEENT, heart, lungs, breast (optional), abdomen, 
external genitalia (optional), extremities, neurologic function, back and lymph nodes.  Targeted physical exam includes the review of the following body 
systems: skin, heart, lungs, abdomen and examination of body systems where there are symptom complaints by the subject.
f.
Chest x-ray may be performed up to 12 weeks prior to screening.  Official reading must be located in the source documentation.
g.
Colonoscopy  to be completed for a subject within approximately 10 days prior to baseline visit, and preferably within 5 to 7 days prior to baseline to allow 
stool data collection for Mayo score calculation and to obtain endoscopic subscore report from the Central Reader.  The endoscopic subscore from the 
Central Reader will be used to determine eligibility. 
h.
Total Mayo score will be based on the centrally-read endoscopic subscore, stool frequency, rectal bleeding and physician’s global assessment.
i.
The subject stool diary to collect stool frequency and rectal bleeding will be collected daily through an e-Diary.
j.
To be performed locally or at the central laboratory.  The detection of C. difficile by toxigenic stool culture [stool culture followed by detection of toxin] is 
considered the gold standard for the diagnosis of the colonization or infection with pathogenic C. difficile.  Comparable sensitivity may be achieved by 
direct testing of stool via point of use rapid membrane enzyme immunoassay card for both C. difficile toxin A and B and GDH antigen on a card. Use of the 
card for point of care screening is encouraged where permitted by local regulation.  Molecular techniques such as PCR for detection of toxin RNA are also 
acceptable alternatives.
k.
Per local regulations. To be assayed locally. Confirmation and documentation of a negative HIV test result within 12 months prior to screening will be 
accepted.  Hepatitis testing and analysis (HBsAg, total HBcAb, HCV Ab confirmed by HCV RNA) will be performed by the central laboratory.
l.
To be assayed locally.  A documented negative PPD test within 12 weeks before screening is acceptable.  IGRA official reading and method or test must be 
located in the source documentation.
m. Serum pregnancy testing at screening and urine pregnancy testing at other scheduled visits are required only for female subjects of childbearing potential.  
Follicle stimulating hormone (FSH) test to be performed at screening to confirm postmenopausal status in female subjects who have been amenorrheic for at 
least 12 consecutive months.
n.
The screening labs may be repeated once if necessary to confirm eligibility.
p.
At dosing visits, PK samples will be collected preferably after vital signs data and within approximately 30 minutes prior to dosing and 1 hour post-dose (at 
end of the infusion); biomarker samples will be collected pre-dose.
r.
Subjects with AEs as a result of positive ADA/NAbs may be requested to return for additional follow-up for up to 3 months after the follow-up/EOS visit
and will have PK and ADA/NAb samples drawn for analysis. Other assessments may also be performed during these visits as appropriate depending upon 
the actual AE that is experienced. 
s.
Subjects will remain at the study site for observation for a minimum of 2 hours after the end of PF-06480605 infusion.
C
C
C
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1. INTRODUCTION
IBD is a chronic inflammatory condition of the gastrointestinal tract that affects five million 
people worldwide.  IBD presents as one of two major forms, UC or Crohn’s Disease (CD).  
UC is characterized by continuous inflammation that is localized to the colon.  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. 
The incidence rates of UC in North America have been reported as high as 19.2 per 100,000 
persons/year and prevalence as high as 248/100,000.2  It occurs more frequently in 
Caucasians and affects females about 35% more often than males.3  Although UC can occur 
at any age, the incidence peaks between 15 to 25 years with a second peak between 55 to 
65 years.4  UC is a lifelong condition with a serious effect on the quality of life.  Current 
treatment primarily consists of 5-aminosalicylic acid (5-ASA), corticosteroids, 
immunosuppressive agents (azathioprine/6-mercaptopurine), or biologic agents (anti-TNF or 
anti-integrin antibodies).  However, despite recent advances, more effective pharmacological 
treatment is needed to induce and maintain remission. 
1.1. Mechanism of Action/Indication
PF-06480605 is a fully human neutralizing antibody against TL1A, a member of the TNF
family of cytokines.  PF-06480605 contains three mutations in the Fc region to reduce 
effector function.  Its mechanism of action is to neutralize the binding and subsequent 
signaling of TL1A to its functional receptor DR3.
PF-06480605 is currently being developed for the treatment of IBD.
1.2. Background and Rationale
1.2.1. Drug Development Rationale
Although the exact cause of UC remains unclear, inhibition of pro-inflammatory cytokines 
and integrins have proven to deliver some therapeutic benefit.  The first biologic therapy 
approved for UC was infliximab, a chimeric IgG1 antibody against TNF-.  In the ACT1 and 
ACT2 trials, infliximab treatment of refractory moderate to severe UC patients demonstrated 
up to a 24% placebo-corrected clinical remission rate at Week 8.  However, at Week 54, the 
placebo-corrected sustained clinical remission rate had fallen to 18%.5
Patients that are intolerant to or eventually lose response to infliximab can be switched to 
other anti-TNF-therapies, such as adalimumab or certolizumab pegol.  In the ULTRA 1 
and ULTRA 2 trials, adalimumab treatment of refractory moderate to severe UC patients 
demonstrated up to a 10% placebo-corrected clinical remission rate by Week 8.  At Week 52, 
this rate was reported as 8%.6  
The anti-integrin antibodies, namely vedolizumab, represent another class of drugs that have 
been approved for treatment of UC.  In the GEMINI 1 trial, vedolizumab treatment of 
refractory moderate to severe UC patients demonstrated a placebo-corrected clinical 
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remission rate of 11.5% at Week 6.7  However, at Week 54, the placebo-corrected clinical 
remission rate was as high as 29.1%.  Taken together, alternative therapies still remain a 
critical unmet medical need for UC patients.
The TL1A/DR3 pathway has been implicated in the regulation of pathogenic Th1, Th2, Th9
and Th17 T-cells, and of NK and NK-T cell responses, in immune-mediated diseases.  The 
TL1A expression on antigen presenting cells (monocytes, macrophages, dendritic cells) and 
DR3 expression on effector cells (ILC2, T-cells, NK and NK-T cells) is highly dependent on 
pro-inflammatory conditions.  Moreover, data from nonclinical species and humans implicate 
TL1A in the pathophysiology of IBD.1
1.2.2. Safety Data
1.2.2.1. Non-Clinical Safety
Standalone safety pharmacology studies were not conducted with PF-06480605.  Safety 
pharmacology endpoints were incorporated into the design of the 3-month Good Laboratory 
Practice (GLP) repeat-dose toxicity studies.
Toxicity studies were conducted in CD-1 mice and cynomolgus monkeys and included 
exploratory and 3-month (13 weeks) GLP repeat-dose toxicity studies (with a 3 month 
recovery phase).  The intravenous (IV) and subcutaneous (SC) routes of administration were 
selected for the in vivo toxicity studies as they are the routes of clinical administration.  In 
addition, a series of in vitro immunotoxicity screening studies were conducted on 
PF-06480605 (Fc and C1q binding, human lymphocyte activation, and human cytokine 
release assay [CRA]) and preliminary immunohistochemical and GLP tissue cross-reactivity 
studies were conducted in a panel of CD-1 mouse, cynomolgus monkey, and normal human 
tissues.
PF-06480605 was administered to mice and cynomolgus monkeys once weekly via the IV 
and SC routes up to 3 months in duration (up to a total of 14 doses).  The 
no-observed-adverse-effect levels (NOAELs) in the 3-month GLP repeat-dose toxicity 
studies were the highest doses tested, which were 250 and 300 mg/kg/week for both IV and 
SC routes in mice and cynomolgus monkeys, respectively. 
The findings in the exploratory toxicity studies were generally consistent with those observed 
in the GLP studies.  However, in one exploratory study in mice, four female mice died 
following PF-06480605 administration at the low and intermediate-dose groups.  The deaths 
of the three animals at 1 mg/kg/week occurred on Days 15, 22, and 29 shortly after test 
article administration.  The single animal at 10 mg/kg/week also died shortly after test article 
administration on Day 22.  Because the deaths did not occur in a dose-responsive manner, no 
deaths were seen in another 30-day mouse exploratory study, and no test article-related 
deaths were seen in the 3-month GLP repeat-dose toxicity study at doses up to 
250 mg/kg/week, the deaths were considered unrelated to direct toxicity of the test article.  
Although ADAs were not evaluated in this study, based on timing of the deaths, the inverse 
dose relationship, the administration of a human antibody to a mouse, and the lack of overt 
clinical signs of toxicity, the cause of death was consistent with immunogenicity.  
Immunogenicity in animals is not considered predictive of immunogenicity in humans.8
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Test article-related, nonadverse higher serum globulin concentrations were observed for both 
IV and SC routes in the 3-month GLP studies in mice and cynomolgus monkeys and were 
associated with higher total protein values and/or lower albumin/globulin ratios.  The higher 
serum globulin concentrations, increased total protein values, and lower albumin/globulin 
ratios were considered most likely to represent the presence of PF-06480605 mAb.  In 
addition, findings consistent with an inflammatory process (eg, increased neutrophil counts, 
fibrinogen concentrations, or incidence of microscopic inflammatory lesions), which can 
result in increased globulin concentrations, were not observed.  The higher serum globulin 
concentrations, increased total protein values, and lower albumin/globulin ratios reversed by 
the end of the recovery phase for mice administered 250 mg/kg/week IV and cynomolgus 
monkeys administered 300 mg/kg/week, the only groups evaluated for recovery phase.  Test 
article-related, nonadverse higher absolute reticulocyte counts and red blood cell distribution 
width (RDW) values were also observed in mice at 250 mg/kg/week SC.  These changes 
were considered indicative of increased red blood cell (RBC) turnover, as reticulocytes are 
younger and larger RBCs and were not considered adverse due to the small magnitude of 
change.  Higher mean absolute reticulocyte counts and higher RDW values were not 
observed in mice administered PF-06480605 by the IV route (all dose levels), and there were 
no other test article-related effects on hematological parameters.  In addition, no test 
article-related effects were noted on hematological parameters in the 3-month toxicity study 
in cynomolgus monkeys. 
There were no test article-related effects on the modified Irwin test, locomotor activity, and 
body temperature in mice and no test article-related effects on electrocardiograms (ECGs), 
heart rate, respiration rate, and body temperature in cynomolgus monkeys in the 3-month 
GLP studies. 
In the 3-month GLP studies, the NOAELs were the highest doses tested, which were 250 and 
300 mg/kg/week for mouse and cynomolgus monkeys, respectively, for both IV and SC 
routes.  The exposure margins (based on the average concentration for the dosing interval 
[Cav]) at these NOAELs in mice were 21x and 15x for IV and SC, respectively, and in 
cynomolgus monkeys were 54x and 37x, for IV and SC, respectively, relative to the 
500 mg IV dosage exposure at steady state to be evaluated in this study.  Similarly, for Cmax, 
the exposure margins at these NOAELs in mice were 29x and 12x for IV and SC, 
respectively, and in cynomolgus monkeys were 59x and 30x respectively. In vitro, 
PF-06480605 caused an increase in cytokine release (1 or more of the 3 cytokines evaluated 
[IFN-, IL-6, and TNF-]) in the solid phase cytokine release assay (CRA) in most human 
donors that was greater than that observed for the isotype and negative controls, but was 
substantially lower than that observed with the positive control antibodies (anti-CD3 mAb 
and anti-CD28 superagonist mAb), which have been shown to produce cytokine release in 
vivo in humans.  However, PF-06480605 did not elicit test article-related cytokine release in 
the in vitro soluble phase human CRA.  No test article-related effect on serum cytokine levels 
was observed in the 3-month GLP toxicity studies in mice and cynomolgus monkeys. 
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In the GLP tissue cross-reactivity study, a large number of tissues had staining in the human, 
mouse, and cynomolgus monkey tissue panels.  The staining observed in the human tissue 
panel was generally similar to that seen in the mouse and cynomolgus monkey tissue panels.  
Staining was primarily observed only at the highest test article concentrations (5 g/mL) and 
may represent nonspecific binding and/or low affinity binding to unrelated epitopes.  The 
majority of staining observed was cytoplasmic in nature, and it is unlikely that the cytoplasm 
and cytoplasmic structures would be accessible to the test article in vivo.  No adverse 
findings were observed in the dosing phase of the 3-month GLP repeat-dose toxicity studies 
conducted in mice and cynomolgus monkeys, which provides further support that the 
staining observed in the ex vivo tissue cross-reactivity study does not translate in vivo. 
The nonclinical safety profile of PF-06480605 has been adequately characterized in vitro and 
in mice and cynomolgus monkeys in vivo to support clinical trials with dosing up to 
3 months in duration.  The only finding in the 3- month toxicity studies was in the mouse 
study.  If the exposure limit is determined as 1/10th of the exposure at the highest dose tested 
in 3-month mouse IV study ie, Cmax = 869 g/mL, Cav = 459 g/mL, for the proposed 
regimen of 500 mg Q2W, the corresponding exposure margins for Cmax and Cav at steady 
state is predicted to be 2.9 and 2.1-fold respectively. 
A preliminary embryo, fetal, and developmental toxicity study (pEFD) has been completed.  
PF-06480605 was intravenously administered by bolus injection to pregnant Crl:CD1(ICR)
female mice once daily on gestation day (GD) 6 and 12 at 0, 20, 250, or 450 mg/kg/dose. 
The maternal and developmental no-observed-adverse-effect level (NOAEL) for PF-
06480605 was 450 mg/kg/dose, the highest dose tested.  Also, there were no findings in male 
or female reproductive organs in the 3 month toxicity studies in mice and cynomolgus 
monkeys.  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.  Women of childbearing potential are eligible for the B7541002 study provided that 
these women utilize two highly effective methods of contraception as outlined in Section 4.3.
1.2.3. Previous Human Experience
1.2.3.1. Subject Disposition
A total of 92 healthy subjects, 60 and 32 subjects in single ascending dose (SAD) and 
multiple ascending dose (MAD) periods, respectively, were assigned to and received study 
treatment (PF-06480605 or placebo) in the completed first-in-human (FIH) study B7541001.  
The doses of PF-06480605 tested were 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 600 mg, 
and 800 mg (as single IV doses) and 30 mg, 100 mg, 300 mg (as multiple SC doses), and 
500 mg IV (as multiple IV doses).  Six (6) subjects discontinued from the study:  3 subjects 
each from the SAD period and the MAD period, which included 1 placebo subject from each 
period.  There were no study discontinuations attributed to treatment-related AEs.  There 
were 2 subjects who were lost to follow-up; one subject in SAD PF-06480605 100 mg cohort 
and one subject in SAD PF-06480605 600 mg cohort.  Additionally, there were 2 subjects 
who were no longer willing to participate in the study; one subject in MAD PF-06480605 
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30 mg cohort and one subject in the placebo group.  One subject in the placebo group 
discontinued due to other reasons (withdrawn at investigator request, non-AE).
1.2.3.2. Pharmacokinetics Results
Following single IV infusion dosing of PF-06480605 under fasted conditions at doses 
ranging between 1 mg and 800 mg, median time to reach maximum concentration (Tmax)
occurred at 1.5 to 2 hours following the end of a 1-hour infusion.  After reaching the 
maximum observed concentration (Cmax), the concentration time profile exhibited a 
multiphasic decline over time, with mean terminal half-life (t1/2) values ranging between 6 
and 23 days.  Mean t1/2 values at the lower doses appeared to be shorter than those observed 
at the higher doses which may be due in part to immunogenicity and/or sensitivity of the 
assay (more quantifiable serum concentrations above the limit of quantification at later time 
points for the higher doses). 
Geometric mean dose normalized area under the curve (AUC) showed an upward trend with 
an increase in dose following single IV doses with greater than dose proportional increases 
across the 1 mg to 800 mg dose range.  Dose normalized Cmax appeared to increase in 
approximately dose proportional manner across the dose range studied. 
Drug clearance (CL) following IV dosing of PF-06480605 appeared to decrease as the doses 
increased, with mean CL value of 0.018 L/hr at the 1 mg dose and 0.007 L/hr at the 800 mg 
dose.  Volume of distribution at steady state (Vss) for IV dosing was low, with mean Vss 
values ranging between 3.4 and 5.5 L across all doses indicating that drug is localized mainly 
to the plasma volume. 
Between subject variability in PF-06480605 exposure was low to moderate, based on 
geometric %CV and ranged between 12% and 33% for the area under the concentration-time 
curve from time 0 to infinity (AUCinf) and 8% to 26% for Cmax.
Following repeat SC dose administration of PF-06480605 at 30 mg, 100 mg, and 300 mg 
doses once every 2 weeks for a total of 3 doses, absorption from the site of injection was 
variable, with peak serum concentrations achieved within a median Tmax of 96 to 216 hours 
post-dose on Day 1, 192 to 335 hours post-dose on Day 15, and 48 hours post-dose on 
Day 29. 
Dose normalized PK exposure (as measured by geometric mean area under the curve over the 
dosing interval [AUCtau] and Cmax) on Day 1 increased in a dose proportional manner with an 
increase in dose, however exposure on Days 15 and 29 trended toward greater than dose 
proportional increases across the 30 mg to 300 mg SC doses.  Estimated bioavailability (F) 
values based on geometric mean AUCtau 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. 
Overall, observed serum exposures (mean AUCtau and Cmax) on Days 15 and 29 were higher 
than those observed on Day 1 following a single dose.  Mean observed accumulation ratios 
(Rac) based on geometric mean AUCtau on Day 29 ranged between 2.4 and 3.2, and Rac for 
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Cmax (Rac, Cmax) based on geometric mean Cmax on Day 29 ranged between 2.3 and 4.2, 
indicating that some drug accumulation does occur following multiple SC dosing every 
2 weeks at doses ranging between 30 mg and 300 mg.  Apparent CL for SC dosing (CL/F) 
and apparent volume of distribution for SC dosing (Vz/F) geometric mean values for the 
100 mg to 300 mg SC doses (individual values for 30 mg SC dose) on Day 29 were 
approximately similar across all 3 SC doses, with mean CL/F and Vz/F values ranging 
between 0.013 and 0.018 L/hr and 4.7 and 8.5 L, respectively.  Mean t1/2 values for the SC 
doses on Day 29 ranged between 8.7 and 21 days with the longer t1/2 values observed at the 
100 mg and 300 mg doses. 
Following multiple dose administration of a 500 mg IV dose once every 2 weeks for a total 
of 3 doses, mean Cmax values on Day 1, Day 15, and Day 29 were observed slightly later than 
the end of a 1-hour infusion (median Tmax ranged between 1.54 and 4.08 hours post-dose).  
Higher geometric mean AUCtau values were observed on Days 15 and 29 compared to Day 1 
with similar Cmax values observed across all dosing days.  Mean Rac based on geometric 
mean AUCtau on Day 29 was 2.1, and Rac, Cmax based on geometric mean Cmax on Day 29 
was 1.4, indicating that there is slight drug accumulation following multiple IV dosing every 
2 weeks.  CL and Vss geometric mean values on Day 29 were 0.008 L/hr and 5.6 L, 
respectively.  Mean t1/2 was 20 days. 
Between subject variability in PF-06480605 exposure on Day 29 for the SC and IV doses 
based on geometric %CV ranged between 14% and 49% for AUC and 7% to 74% for Cmax, 
with the higher variability observed for the SC dosing compared to the IV dose. 
The PK parameters reported above were summarized by cohort, irrespective of 
immunogenicity status of the subject.  Importantly, the impact of immunogenicity on PK at 
the higher doses was not significant as the CL was similar after single (300, 600, 800 mg IV)
or comparable multiple doses (500 mg IV) and each showed CL similar to typical IgG1 
monoclonal antibodies.
1.2.3.3. Immunogenicity Results
The incidence of ADA ranged from 50% to 100% for SAD and MAD cohorts.  In subjects 
receiving PF-06480605, 56 subjects out of 68 subjects were considered to be positive for 
ADA.  The overall confirmed treatment induced incidence rate was 82.4%; however, there 
were 11 subjects for whom PF-06480605 concentrations remained above the assay tolerance 
level throughout the study.  Positive ADA samples were detected as early as 336 hours 
(14 days) post-dose in the SAD cohorts and on Day 29 in the MAD cohorts.
The incidence of neutralizing antibody (NAb) ranged from 0% for 2 SAD and 2 MAD 
cohorts to 100% for the 3 mg IV cohort.  In subjects receiving PF-06480605, 24 subjects out 
of 68 subjects were considered positive for NAb.  The overall confirmed NAb incidence rate 
was 35.3%.  Positive NAb samples were detected as early as 672 hours (28 days) post-dose 
in the SAD cohorts and 1680 hours (70 days) post-dose in the MAD cohorts.  Where data 
was available, mean serum PF-06480605 concentrations were lower in subjects identified as 
ADA positive, compared to subjects identified as ADA not-positive, and were even lower in 
subjects with NAb log titer 0.70.
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Differences in mean serum PK parameters, namely exposure, between subjects identified as 
ADA positive and ADA not-positive as well as between subjects with NAb log titer 
<0.70 and 0.70 were more apparent for subjects in MAD cohorts but no direct conclusions 
were able to be drawn from the data. 
In Study B7541001, there were no immunogenicity associated safety signals including 
injection site reactions or hypersensitivity.  Likewise, there were no significant findings from 
the Cytokine Release Assay (CRA).  Furthermore any impact of immunogenicity on PK and 
PD was restricted to the lower doses of 30 mg.  At the higher doses there was no significant 
impact as the CL after single (300 mg, 600 mg, 800 mg) or repeat doses of the 500 mg IV 
dose level where CL was similar to typical IgG1 monoclonal antibodies.
1.2.3.4. Safety Results
There were no deaths, SAEs, severe AEs, AEs resulting from ADA/Nabs, or subjects with 
dose reduced or temporary discontinuations due to AEs during the FIH study with 
PF-06480605.  Additionally, there were no clinically significant laboratory abnormalities
(eg, CRA), vital signs, or ECGs. 
In the single dose period, there were 45 all causality TEAEs reported by 21 subjects out of 
the 44 subjects treated with PF-06480605.  Of these, 15 events were determined to be 
treatment-related and were reported by 13 subjects.  There were 20 all causality TEAEs 
reported by 7 subjects out of the 16 subjects treated with placebo, of which 9 events were 
determined to be treatment-related and were reported by 5 subjects. 
In the multiple dose period, there were 44 all causality TEAEs reported by 17 subjects out of 
the 24 subjects treated with PF-06480605.  Of these, 21 events were determined to be 
treatment-related and were reported by 11 subjects.  There were 17 all causality TEAEs 
reported by all of the 8 subjects treated with placebo, of which 6 events were determined to 
be treatment-related and were reported by 5 subjects. 
Overall, headache was the most commonly reported all causality (7 PF-06480605 subjects 
and 3 placebo subjects) and treatment-related (5 PF-06480605 subjects) TEAE.  The second 
most commonly reported treatment-related TEAE was abdominal pain which was reported 
by 3 PF-06480605 subjects and 1 placebo subject. 
The incidence of TEAEs between cohorts in the SAD period and between cohorts in the 
MAD period was similar.  Overall, there was a higher incidence of treatment-related TEAEs 
in MAD cohorts compared with SAD cohorts, although the incidence of TEAEs did not 
increase with higher doses of PF-06480605.  Headache was the most commonly reported all 
causality and treatment-related TEAE. 
The majority of TEAEs were mild in severity.  There was a higher incidence of moderate 
severity TEAEs reported by subjects in MAD cohorts compared with SAD cohorts.  The 
study’s only treatment-related moderated severity TEAE, abdominal pain, was reported by a 
subject from a MAD cohort.  There were no severe TEAEs reported.  There were no injection 
site or hypersensitivity reactions reported.
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There were no subjects from the SAD period who discontinued from the study due to an AE.  
In the MAD period, there was 1 subject who discontinued from the study due to a treatment 
unrelated AE, pyuria, on study Day 14.  The event was determined to be mild and the subject 
recovered in one day. 
Complete information for this compound may be found in the Single Reference Safety 
Document (SRSD), which for this study is the Investigator’s Brochure (IB).
1.3. Rationale
1.3.1. Study Rationale
This multicenter, single arm (non-placebo controlled), two-stage study will be the first use of 
PF-06480605 in subjects with moderate to severe UC.  The objectives of this study are to 
evaluate the safety, tolerability, PK and efficacy (based on Mayo endoscopic subscore) of 
PF-06480605 at 500 mg IV administered Q2W for a total of 7 doses.
The current non-clinical toxicology package available will support a 12-week treatment 
period.  To mitigate the need for a placebo arm, endoscopic improvement, a more objective
endpoint, with lower placebo rates than clinical disease activity scores, was selected as the 
primary endpoint.  All colonoscopies will be read by a Central Reader who will be blinded to 
study treatment.  An induction period of 12 weeks of dosing with primary endpoint at 
Week 14, which is greater than the traditional 8 weeks, was chosen to increase the likelihood 
of achieving endoscopic improvement.  Following completion of dosing at 12 weeks, the 
subjects will be followed for an additional 14 weeks to characterize PK and immunogenicity.
During the endoscopic evaluations, intestinal biopsies will be obtained and interrogated to 
provide evidence for pharmacological modulation of the TL1A pathway and to define 
parameters that might be used to enable a precision medicine strategy in future clinical trials.  
Furthermore, the peripheral blood and stool will be profiled to provide correlative peripheral 
biomarkers that could complement the precision medicine approach in intestinal biopsies. 
In Study B7541001, there were no immunogenicity associated safety signals or laboratory 
abnormalities and any impact on exposure was restricted to the low dose groups (30 mg).  
In Study B7541002, a dose level is being evaluated that did not show any immunogenicity 
related impact on exposure, and is predicted to achieve >90% neutralization of sTL1A at 
trough throughout the dosing period.  Further in study B7541002, the UC patients may be on 
immunosuppressive therapy which could further reduce the incidence of immunogenicity.
PK, PD, ADA and NAb will be monitored at various time points to characterize the potential 
impact of immunogenicity and patients with AEs as a result of positive ADA/NAbs may be 
requested to return for additional follow-up for up to 3 months after the follow-up/EOS visit.
In addition, historical internal data may be utilized to compare with the safety data from this 
study in order to place the safety findings in context given this is a single arm study.
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1.3.2. Dose Rationale
For Study B7541002, 500 mg administered IV Q2W for a total of 7 doses is being proposed 
based on the following:  this dose level has been administered in humans and the PK of 
PF-06480605 is typical of IgG1 monoclonal antibodies; at this dose no impact of 
immunogenicity on PK was evident; based on modeling this dosage is expected to show
target modulation that might drive pharmacology; and this dosage would provide a safety 
margin of 2.9 and 2.1-fold for Cmax and Cav respectively compared to 1/10th of the maximum 
exposure (29 and 21-fold relative to the NOAEL) tested in 3-month mouse toxicity study.
The dosage of 500 mg Q2W has been administered in Study B7541001 and the CL and Vss
geometric mean values on Day 29 of 0.008 L/hr and 5.6 L, respectively, and mean t1/2 of 
20 days for PF-06480605 following administration of 500 mg Q2W are similar to the values 
for other typical IgG1 therapeutic monoclonal antibodies as well as endogenous IgG1.10  For 
dosage administrations >30 mg in Study B7541001, a modified quasi-steady state target 
mediated drug disposition model accounting for any impact of immunogenicity on exposure, 
adequately characterized the PF-06480605 and sTL1A serum concentrations. 
Additionally, assuming that neutralization of TL1A will translate into efficacy, a site of 
action model was used to predict the degree of neutralization of sTL1A by PF-06480605 
(sTL1A coverage) in serum and gut.  The percentage of patients achieving a 90% sTL1A 
(P90) coverage for different regimens were simulated including administration of 150 and 
300 mg SC Q2W and 500 mg IV Q2W for 24 weeks.  The P90 values following 
administration of 150 mg SC, 300 mg SC and 500 mg IV Q2W for 24 weeks were 61%, 
76.3% and 87.2%, respectively.  To maximize the chances of seeing efficacy through 
neutralization of TL1A, 500 mg of PF-06480605 administered IV Q2W was selected as the 
dosage regimen in Study B7541002. 
Assuming that PF-06480605 PK is similar between healthy volunteers and moderate to 
severe UC patients, PK simulations suggest that PF-06480605 administered as 500 mg Q2W 
for a total of 7 doses would provide a median (50th prediction interval) of 299 g/mL and 
216 g/mL for Cmax and Cav at steady state respectively.  When compared to 1/10th of the 
exposures at the highest mouse IV dose in the 3-month GLP toxicity studies, it is anticipated 
that this dosage of 500 mg Q2W will maintain a 2.9 and 2.1-fold (29 and 21-fold relative to 
the NOAEL) safety margin for Cmax and Cav respectively.
1.3.3. Summary of Benefits and Risks
IBD is a serious and potentially life-threatening disease. Overall, the safety profile observed 
during the Phase 1 program for PF-06480605 appears to be acceptable at dosages up to 
800 mg administered intravenously as single doses and up to 500 mg administered 
intravenously as multiple doses. 
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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Primary Objectives

To evaluate the safety and tolerability of PF-06480605 in subjects with moderate to 
severe UC.

To evaluate the efficacy of PF-06480605 in induction of endoscopic improvement (as 
assessed by Mayo endoscopic subscore) at Week 14 in subjects with moderate to 
severe UC.
2.1.2. Secondary Objectives

To evaluate the efficacy of PF-06480605 in induction of remission at Week 14 
(defined as a total Mayo score 2 with no individual subscore >1) in subjects with 
moderate to severe UC.

To evaluate the efficacy of PF-06480605 in induction of endoscopic remission at 
Week 14 (defined as a Mayo endoscopic subscore of 0) in subjects with moderate to 
severe UC.

To describe the PK of PF-06480605 in subjects with moderate to severe UC.

To evaluate the immunogenicity of PF-06480605 in subjects with moderate to severe 
UC.

To evaluate disease and pathway related biomarkers (ie, hsCRP and fecal 
calprotectin), and serum total sTL1A.
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2.2. Endpoints
2.2.1. Primary Endpoints

Safety and tolerability of PF-06480605:  TEAEs, withdrawal due to AEs, and SAEs 
will be reported.

Endoscopic improvement at Week 14 (defined as a Mayo endoscopic subscore of 0 
or 1, and without friability).
2.2.2. Secondary Endpoints

Remission at Week 14 (defined as a total Mayo score 2 with no individual subscore 
>1).

Endoscopic remission at Week 14 (defined as a Mayo endoscopic subscore of 0).

PF-06480605 plasma concentrations.

Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies 
(NAbs). 

Change from baseline in fecal calprotectin.

Change from baseline in hsCRP.

Change from baseline in serum total sTL1A.
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3. STUDY DESIGN
3.1. Study Overview
This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe UC.  
Subjects will receive 500 mg of PF-06480605 intravenously Q2W for a total of 7 doses.  At 
the end of the first stage (12 evaluable subjects with a Week 14 colonoscopy), an IA will be 
performed for an early efficacy assessment.  Enrollment in the second stage will be stopped if 
the futility criteria are met and any ongoing subjects in the second stage will be moved to the 
follow-up period.  Otherwise, the study will continue to enroll additional subjects in the 
second stage for final efficacy assessment.  An early PK readout of PF-06480605 serum 
concentrations will be conducted after at least 6 subjects have completed the Week 4 visit to 
confirm that the predicted exposures of PF-06480605 in UC patients are consistent with 
expected values, based on the healthy subject PK data.  Following this early PK readout 
analysis, dose may be modified to match the exposures observed in healthy volunteers 
receiving 500 mg/kg IV (Study B7541001).  The study will include an additional research 
component involving collection of biological samples and planned analysis for de-identified 
exploratory biomarker and immunogenicity analysis.
Women of childbearing potential (WOCBP) will be eligible for this study  provided these 
women use two highly effective methods of contraception, as outlined in Section 4.3.
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Stopping Rules
Individual stopping rules will be implemented to further evaluate safety and feasibility of 
study continuation, as described below:  

If 2 subjects receiving PF-06480605 develop the same adverse laboratory event with 
Common Terminology Criteria for Adverse Events (CTCAE V4.03) Grade 3 or 
higher, or if 1 subject develops a laboratory adverse event with a CTCAE Grade 4 or 
higher, then the study may be terminated.  

If 2 subjects experience an ECG abnormality defined as a prolonged QTcF of 
>500 msec over baseline assessment, then the study may be terminated.  If a single 
subject experiences a prolonged QTcF of >500 msec over baseline assessment, then 
this subject will be discontinued from the study.  
3.2. Duration of Subject Participation
The duration of participation for eligible subjects will be approximately 8 months, including 
a screening period of up to 6 weeks, a 12 week treatment period, and a follow-up period 
ending 14 weeks after the last dose of IP. Subjects with AEs as a result of positive 
ADA/NAbs may be requested to return for additional follow-up for up to 3 months after the 
follow-up/ EOS visit.  During the treatment period, subjects will visit the site every 2 weeks 
(3 days) for IP administration (7 visits), and then will return to the site every 4 weeks 
(7 days) through Week 24 and again at Week 26, for follow-up visits (5 visits). 
3.3. Approximate Duration of Study
This study is estimated to complete in approximately 32 months, maximum, allowing for an 
estimated 18-24 months of enrollment and approximately 8 months on study.
3.4. Planned Number of Subjects
This study has two stages.  In the first stage, it is planned to have 12 evaluable subjects with 
an endoscopic score at Week 14 for futility assessment.  If futility criteria are not met, 
recruitment will continue until approximately 36 total evaluable subjects complete the study 
with a final colonoscopy at Week 14.
4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects 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 subject is suitable for this protocol.
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
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Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures.
3. Male and/or female subjects between 18 and 75 years of age at the time of 
informed consent. 
4. Male subjects able to father children and female subjects of childbearing potential and 
at risk for pregnancy must agree to use two highly effective methods of contraception 
throughout the study and until the Week 26 visit (or 98 days after the last dose of IP).
Women of childbearing potential (WOCBP) will be eligible for this study provided 
these women use two highly effective methods of contraception throughout the study 
and until the Week 26 visit (or 98 days after the last dose of IP), as outlined in 
Section 4.3.  Female subjects who are not of childbearing potential (ie, meet at least 
1 of the following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or 
Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level confirming the 
post-menopausal state.
Note: For subjects in France, WOCBP are NOT eligible for this study.
5. A diagnosis of UC for 4 months.  A biopsy report must be available to confirm the 
histological diagnosis in the subject’s source documentation.  In addition, a report 
documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided 
colitis, and pancolitis) based upon prior endoscopy must also be available in source 
documentation.
6. Subjects with moderate to severe active UC as defined (via screening colonoscopy) 
by a total Mayo score of 6, with a rectal bleeding subscore of 1 and an endoscopic 
subscore of 2 on the Mayo. 
7. Active disease beyond the rectum (>15 cm of active disease at the screening 
colonoscopy).
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8. Must have inadequate response to, loss of response to, or intolerance to at least one 
conventional therapy for UC:

Steroids;

Immunosuppressants (AZA [azathioprine], 6-MP, or MTX [methotrexate]);

Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab);

Anti-integrin inhibitors (eg, vedolizumab).
For subjects in The Netherlands:  Subjects must have inadequate response to, 
loss of response to, or intolerance to at least one biological therapy, such as an 
anti-TNF inhibitor.
Note: The information below is provided as guidance. Local standards of care, as 
well as investigator assessment should be considered.
Inadequate response to, loss of response to, or intolerance to corticosteroid treatment 
is defined as one or more of the following:

Steroid refractory: persistent symptoms of active disease despite treatment with at 
least one 4-week induction regimen that included a dose of 30 mg prednisone 
(oral) daily for at least 2 weeks or IV for at least 1 week within the previous 
5 years;

Steroid dependent: two failed attempts to taper steroids below a dose equivalent to 
10 mg prednisone (oral) daily;

Steroid intolerant: history of intolerance to corticosteroids (including but not 
limited to Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, 
insomnia, infection) within the previous 5 years.
Inadequate response to, loss of response to, or intolerance to prior 
immunosuppressant treatment is defined by one or more of the following:

Persistent signs and symptoms of active disease despite a history of at least one 
12-week regimen of oral AZA (2-2.5 mg/kg/day) or 6-MP (1-1.5 mg/kg/day) 
and/or MTX (25 mg/week) within the previous 5 years;

History of intolerance to AZA, 6-MP, or MTX (including but not limited to 
nausea/vomiting, abdominal pain, pancreatitis, LFT [liver function testing]
abnormalities, lymphopenia, TPMT [thiopurine methyltransferase] genetic 
mutation, infection) within the previous 5 years.
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Inadequate response to, loss of response to, or intolerance to prior anti-TNF inhibitors 
and anti-integrin inhibitors is defined as one or more of the following:

Persistent signs and symptoms of active disease despite at least one 8-week 
regimen of infliximab (3 intravenous doses 5 mg/kg), or adalimumab 
(subcutaneous doses of 160 mg at Week 0 and 80 mg at Week 2 followed by a 
dose of 40 mg every 2 weeks), or golimumab (subcutaneous doses of 200 mg at 
Week 0 and 100 mg at Week 2, followed by 50 mg or 100 mg every 4 weeks), or 
vedolizumab (intravenous doses of 300 mg at Weeks 0, 2, and 6).

Note:  There is no specific requirement for a subject to “washout” of a current 
treatment and no patient should be actively removed from prohibited medications 
in order to meet study inclusion/exclusion criteria.  
9. Subjects currently receiving the following treatment for UC are eligible provided they 
have been on stable doses as described below:

Oral 5-ASA or sulfasalazine stable dose for at least 4 weeks prior to baseline.  If 
oral 5-ASA treatment has been recently discontinued, it must have been stopped 
for at least 2 weeks prior to total Mayo score screening procedures.

Oral corticosteroids (prednisone equivalent up to 20 mg/day; budesonide up to 
9 mg/day) stable dose for at least 2 weeks prior to baseline.  If oral corticosteroids 
have been recently discontinued, they must have been stopped at least 2 weeks 
prior to total Mayo score screening procedures.  Decreases in steroid use due to 
AEs are allowed.

6-MP or AZA (2.5 mg/kg) stable dose for 8 weeks prior to baseline.  Decreases 
due to AEs are permitted.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Subjects with a diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, 
diverticular disease associated with colitis, microscopic colitis or CD.  Subjects with 
clinical findings suggestive of CD (eg, fistulae, granulomas on biopsy) are also 
excluded.
2. Subjects with an imminent need for surgery or with elective surgery scheduled to 
occur during the study.
3. Subjects with colonic dysplasia or neoplasia.
4. Subjects with toxic megacolon.
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5. Subjects with primary sclerosing cholangitis.
6. Subjects with known colonic stricture.
7. Subjects with history of colonic or small bowel stoma.
8. Subjects with a history of colonic or small bowel obstruction or resection.
9. Abnormal findings on the chest x-ray film performed routinely before initiating a new 
biologic therapy, such as presence of tuberculosis (TB), general infections, heart 
failure, or malignancy.  Chest x-ray examination may be performed up to 12 weeks 
prior to screening.  Documentation of the official reading must be located and 
available in the source documentation. 
10. Any current evidence of untreated latent or active TB infection, evidence of prior or 
currently active TB by chest x-ray, residing with or frequent close contact with 
individual(s) with active TB.  Subjects who have a positive Mantoux (PPD) 
tuberculin skin test or a positive Interferon Gamma Release Assay (IGRA to be tested 
at the site’s local lab where feasible) during screening or within 12 weeks prior to 
randomization.  The following are acceptable assays:  QuantiFERON-TB Gold test 
(QFT-G), QuantiFERON-TB Gold In-Tube test (QFT-GIT) and T-SPOT-TB test 
during screening or within 12 weeks prior to screening. 

A positive Mantoux tuberculin skin test is defined as 5 mm of induration (or as 
defined by country specific or local standards) at 48-72 hours without 
consideration of prior Bacillus Calmette-Guerin (BCG) vaccination.  
Documentation of the dose and product used for the Mantoux tuberculin test as 
well as the official test reading must be obtained and available in the subject’s 
source documentation.

An IGRA is preferred for subjects with a prior BCG vaccination (to be tested by a 
site’s local lab where feasible), but may be used for any subject.  Documentation 
of IGRA product used and the test result must be in the subject’s source 
documentation. 

If 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.

Subjects with repeat indeterminate IGRA results may be enrolled after 
consultation with pulmonary or infectious disease specialist that determines low 
risk of infection (ie, subject would be acceptable for immunosuppressant 
(eg, anti-TNF) treatment without additional action).

Subjects with adequately treated latent tuberculosis infection may be enrolled 
regardless of Mantoux or IGRA results.
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11. Presence of active enteric infections (positive stool culture and sensitivity).  The 
presence of Clostridium difficile or pseudomembranous colitis.  Known active 
invasive fungal infections such as histoplasmosis or parasitic infections.  Subjects 
with clinically significant underlying disease that could predispose the subjects to 
infections.  A history of serious infection (requiring parenteral antibiotic and/or 
hospitalization) within 4 weeks before Day 1.  Pyoderma gangrenosum is allowed. 
12. Known history of human immunodeficiency virus (HIV) based on documented 
history with positive serological test, or positive HIV serologic test at screening, 
tested at the site’s local lab.  (Note:  a documented negative HIV test within 1 year of 
screening is acceptable and does not need to be repeated).
13. Presence of transplanted organ.  Skin grafts to treat pyoderma gangrenosum are 
allowed.
14. Significant concurrent medical condition as judged by the investigator at the time of 
screening or baseline visit, including but not limited to the following:

Any major illness/condition or evidence of an unstable clinical condition 
(eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, 
immunologic [eg, Felty’s syndrome], or local active infection/infectious illness) 
that, in the investigator’s judgment will substantially increase the risk to the 
subject if he or she participates in the study.

Cancer or history of cancer or lymphoproliferative disease within the previous 
5 years (other than resected cutaneous basal cell or squamous cell carcinoma that 
has been treated with no evidence of recurrence).

Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) 
and any history of cerebrovascular disease within 24 weeks before screening.

Subjects with current, or a history of QT prolongation would be excluded.

Class III or Class IV heart failure.
15. Prior evidence of liver injury or toxicity due to methotrexate.
16. Abnormality in hematology and/or chemistry profiles during screening:

Positive hepatitis B surface antigen (HBsAg), total hepatitis B core antibody 
(HBcAb; also referred to as anti-HBc), and/or hepatitis C antibody (HCVAb) with 
confirmation by hepatitis C virus ribonucleic acid (HCV RNA).

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
1.5 times the upper limit of normal (ULN).

Total bilirubin level 1.5 times the ULN.
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
Hemoglobin level 80 g/L (8.0 g/dL).

Platelet count 100 x 109/L (100,000 cells/mm3) or 1000 x 109/L 
(1,000,000 cells/mm3).

White blood cell (WBC) count 3.5 x 109/L (3500 cells/ mm3).

Absolute neutrophil count (ANC) <2000 cells/mm3.

Serum creatinine level 177 mol/L (2 mg/dL).

Glycosylated hemoglobin (HbA1C) >10%.
Screening laboratory tests if considered by the investigator to be transient and 
inconsistent with the subject’s clinical condition may be repeated once during the 
screening period for confirmation.
17. Subjects receiving the following therapies within the designated time period or are 
expected to receive any of these therapies during the study period:

>9 mg/day of oral budesonide or >20 mg/day of prednisone or equivalent oral 
systemic corticosteroid dose within 2 weeks prior to baseline.

IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid 
enemas/suppositories within 2 weeks prior to baseline.

Biologics including anti-TNF inhibitors as described below:

Infliximab within 8 weeks prior to baseline.

Adalimumab within 8 weeks prior to baseline.

Golimumab within 8 weeks prior to baseline.

Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline.
For subjects in France:  Subjects must not have received any biologic 
treatment for at least 5 half-lives prior to first dose of PF-06480605.
(eg, infliximab: 47.5 days, adalimumab: 70 days, golimumab: 70 days, 
vedolizumab: 125 days).

Other investigational procedure(s) or product(s), such as immunosuppressants 
used in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or 
tacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.
18. Current or history within 2 years of serious psychiatric disease or alcohol or drug 
abuse.
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19. Subjects who are investigational site staff members directly involved in the conduct 
of the study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees directly involved in the conduct of 
the study.
20. Participation in other studies involving investigational drug(s) within 30 days, or 
5 half-lives of IP (whichever is greater), prior to baseline and/or during study 
participation.
21. Other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or IP
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
22. Pregnant female subjects; breastfeeding female subjects; male subjects with partners 
currently pregnant; male subjects able to father children and female subjects of 
childbearing potential who are unwilling or unable to use two highly effective 
methods of contraception as outlined in this protocol for the duration of the study and 
until the Week 26 visit (or 98 days after the last dose of IP) or longer based on the 
compound’s half-life characteristics.
4.3. Lifestyle Guidelines
Women of childbearing potential (WOCBP) will be eligible for the study provided these 
women use two highly effective methods of contraception throughout the study and until the 
Week 26 visit (or 98 days after the last dose of IP), as outlined below. 
Note: For subjects in France, WOCBP are NOT eligible for this study.
All male subjects who are able to father children and female subjects who are of childbearing 
potential and are sexually active and at risk for pregnancy must agree to use two methods of 
highly effective method of contraception consistently and correctly for the duration of the 
active treatment period and until the Week 26 visit (or 98 days after the last dose of IP). The 
investigator or his or her designee, in consultation with the subject, will confirm that the 
subject has selected two appropriate methods of contraception for the individual subject from 
the permitted list of contraception methods (see below) and instruct the subject in its 
consistent and correct use.  Subjects need to affirm that they meet the criteria for correct use 
of at least 2 of the selected methods of contraception.  The investigator or his/her designee
will discuss with the subject the need to use highly effective contraception consistently and 
correctly according to the Schedule of Activities and document such conversation in the 
subject’s chart.  In addition, the investigator or his or her designee will instruct the subject to 
call immediately if the selected contraception method is discontinued or if pregnancy is 
known or suspected in the subject or the subject’s partner. 
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Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of oral, inserted, injected, implanted or transdermal hormonal 
methods of contraception is allowed provided the subject plans to remain on the same 
treatment throughout the entire study and has been using that hormonal contraceptive 
for an adequate period of time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
or suppository). For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Male sterilization with absence of sperm in the post-vasectomy ejaculate.
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
6. Female partner who meets the criteria for non-childbearing potential, as described 
below:
Female subjects of non-childbearing potential must meet at least one of the following 
criteria:

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or 

Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; and have a serum FSH level confirming the post-menopausal 
state.
All other female subjects (including females with tubal ligations) will be considered 
to be of childbearing potential.
All sexually active male subjects must agree to prevent potential transfer of and exposure to 
drug through semen to their partners by using a condom consistently and correctly, beginning 
with the first dose of IP and until the Week 26 visit (or 98 days after the last dose of IP). 
4.4. 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 site Regulatory binder. 
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To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational compound identifiers, subject study numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigational 
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 investigational 
site and the study team are not available. It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational 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 subject directly, and if a subject calls that number, he 
or she will be directed back to the investigational site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonization (ICH)
guidelines IP is defined as a pharmaceutical form of an active ingredient or placebo being 
tested or used as a reference in a clinical trial, including a product with a marketing 
authorization when used or assembled (formulated or packaged) in a way different from the 
approved form, or when used for an unapproved indication, or when used to gain further 
information about an approved use (ICH E6 1.33).
5.1. Allocation to Treatment
Subject enrollment and assignment of treatment will be managed through the use of a 
centralized Interactive Response Technology (IRT) system or another suitable system. 
During the screening period, subjects are to be assigned a Single Subject Identifier (SSID) 
number via an automated IRT system or another equivalent system managed by Pfizer. 
Subjects who meet all of the eligibility criteria (See Section SUBJECT SELECTION) are 
qualified to participate and receive IP within the study.  At the point of study eligibility and 
enrollment, a subject should be assigned an enrollment or treatment number as allocated via 
the IRT or equivalent system so as to uniquely track their participation in study conduct.
IP will only be administered to subjects who have signed and dated an Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) approved informed consent document 
(ICD) and who have met all eligibility criteria. 
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular subject or affect the order in which subjects are enrolled.
5.2. Subject Compliance
All doses of IP will be administered by the appropriately designated study staff at the 
investigational site.
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5.2.1. Infusion Discontinuation
Treatment of patients with monoclonal antibodies may result in inappropriate immune 
responses and range from mild events with no apparent clinical manifestations to 
life-threatening or catastrophic reactions. Signs and symptoms of these events may develop 
during or shortly after infusion.  As such, subjects must be closely monitored during 
administration of PF-06480605, and for a minimum of 2 hours after administration has 
ended. 
Some of the major safety concerns associated with immunogenicity are anaphylaxis, cytokine 
release syndrome, “infusion reactions”, and non-acute reactions such as delayed 
hypersensitivity; and manifestations may be common among these events. 
The information below is provided as guidance to assess anaphylaxis, but the clinical 
judgment of the investigator should be considered as well.
Anaphylaxis is a serious, acute allergic reaction characterized by certain clinical features. 
Signs and symptoms of anaphylaxis may include: 

Generalized hives, pruritis/itching, flushing, swollen lips/tongue/uvula;

Symptoms of respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia);

Reduced blood pressure (systolic blood pressure of less than 90 mm Hg or greater 
than 30% decrease from baseline) or associated symptoms of end-organ dysfunction 
(eg, hypotonia [collapse], syncope, incontinence);

Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting).
The Sponsor recommends use of the Sampson criteria13 for further guidance regarding the 
diagnosis of anaphylaxis reactions.
If a subject experiences anaphylaxis, IP administration should be discontinued immediately 
and permanently.
If a subject experiences symptoms that may be attributed to hypersensitivity reaction or 
delayed hypersensitivity (eg, fever, rash, arthralgia, myalgia, hematuria, proteinuria, serositis, 
central nervous system complications, or hemolytic anemia) IP infusion should be stopped.  
In the event that symptoms are mild or minor in severity, at the discretion of the investigator, 
the infusion may be restarted at a slower rate if symptoms are resolved within 1 hour after the 
stop of infusion.  If symptoms return, IP should be discontinued immediately and 
permanently. 
In the event that there is an infusion interruption, the entire duration of IP infusion, from the 
initial start of infusion, to the completion of infusion, should not exceed 3 hours.  Subjects 
will receive appropriate treatment at the discretion of the investigator. 
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5.3. Investigational Product Supplies
5.3.1. Dosage Form(s) and Packaging
IP, PF-06480605 Powder for Solution for Injection, 100 mg/vial, is supplied by Pfizer as a 
lyophilized white cake in a sterile, single-use, glass vial with aluminum flip off seal for 
IV administration.
5.3.2. Preparation and Dispensing
See the Dosage and Administration Instructions (DAI) for instructions on how to prepare the 
IP for administration.  IP should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, 
practitioner, or pharmacist) as allowed by local, state, and institutional guidance.
5.4. Administration
PF-06480605 (500 mg) will be administered intravenously as a 60 minute infusion using a 
calibrated infusion pump at Day 1, Week 2 (Day 15), Week 4 (Day 29), Week 6 (Day 43), 
Week 8 (Day 57), Week 10 (Day 71) and Week 12 (Day 85) 3 days during the study for a 
total of up to 7 doses.  IP administration should occur following most study procedures and 
must not be administered as an IV push or bolus.  The start and stop time of the infusion will 
be recorded on the case report form (CRF). The infusion stop time should be recorded as the 
time when the end of the saline flush is complete.  
Subjects should remain at the study site for a minimum period of at least 2 hours for 
observation following end of administration of PF-06480605 infusion.
5.5. Investigational Product Storage 
The investigator, or an approved representative, eg, pharmacist, will ensure that all IP is
stored in a secured area with controlled access under required storage conditions and in 
accordance with applicable regulatory requirements.
IP should be stored in its original container and in accordance with the label.  See the DAI 
for storage conditions of the product once reconstituted.
Storage conditions stated in the IB will be superseded by the storage conditions stated in the 
labeling.
All IP will be shipped to each study site at +2C to +8C.  Upon receipt at the study site, the 
IP should be immediately transferred to a +2C to +8C temperature-monitored refrigerator 
for storage.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of IP receipt throughout the study.  Even for continuous monitoring 
systems, a log or site procedure that ensures active daily evaluation for excursions should be 
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available.  The operation of the temperature monitoring device and storage unit 
(eg, refrigerator), as applicable, should be regularly inspected to ensure it is maintained in 
working order. 
Any excursions from the product label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor.  Once an 
excursion is identified, the IP must be quarantined and not used until the sponsor provides 
documentation of permission to use the IP.  It will not be considered a protocol deviation if 
the sponsor approves the use of the IP after the temperature excursion.  Use of the IP prior to 
sponsor approval will be considered a protocol deviation.
Specific details regarding information the site should report for each excursion will be 
provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the product(s) are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.6. Investigational Product Accountability 
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the IP supplies. 
5.6.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused IP (eg, at the 
site). If destruction is authorized to take place at the study 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.
5.7. Prior Medications
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 and anti-integrins 
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.
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5.8. Concomitant Medication(s) and Treatment(s)
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 subjects will 
be questioned about concomitant medication at each site visit.
Medication(s) administered/taken following the first dose of IP will be documented as 
concomitant medication(s).
5.8.1. Oral Corticosteroids Taken During the Study
Any oral corticosteroids taken during the screening and treatment periods of the study will be 
captured on the appropriate CRF.
5.8.2. Permitted Medications
Subjects will be allowed to use the following medications as detailed below:

Concomitant use of oral 5-ASA or sulfasalazine.  Dose must be stable for at least 
4 weeks prior to baseline and through Week 14.  If oral 5-ASA treatment has been 
recently discontinued, it must have been stopped for at least 2 weeks prior to Total 
Mayo Score screening procedures.

A stable dose of oral corticosteroids (prednisone equivalent up to 20 mg/day; 
budesonide up to 9 mg/day) for at least 2 weeks prior to baseline and through 
Week 14.  If oral corticosteroids have been recently discontinued, they must have 
been stopped at least 2 weeks prior to total Mayo score screening procedures.  Rectal 
steroids are prohibited.  Decreases in steroid use due to AEs are allowed.

A stable dose of immunosuppressants (6-MP or AZA 2.5 mg/kg) for 8 weeks prior 
to baseline and through Week 14.  Decreases due to AEs are permitted.
5.8.3. Prohibited Medications

Any live (attenuated) vaccines from 30 days prior to baseline through Week 14.

IV, intramuscular (IM) (parenteral) or rectal 5-ASA or corticosteroid 
enemas/suppositories from 2 weeks prior to baseline through Week 14.

Prednisone dose >20 mg/day or equivalent oral systemic corticosteroid from 2 weeks 
prior to baseline through Week 14.

Any investigational or marketed biologic immunosuppressive treatments within 
30 days, or 5 half-lives of IP (whichever is greater), prior to baseline and/or during 
study participation.

Oral budesonide >9 mg/day or equivalent from 2 weeks prior to baseline through 
Week 14.
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
Use of immunosuppressants used in transplantation (eg, mycophenolate mofetil, 
cyclosporine, rapamycin, or tacrolimus) from 30 days prior to baseline through 
Week 14.
5.9. Rescue Medication
Following the Week 14 visit, subjects will no longer need to abstain from the medications 
that were prohibited during the screening and induction periods.  High-dose steroids and 
other UC treatments will be permitted after the Week 14 visit.  Biologic treatment(s) should 
not be initiated during the follow-up period without discussion with the sponsor due to the 
long t1/2 of PF-06480605.
Subjects 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 subject requires 
initiation of a new therapy for ulcerative colitis, the subject should be withdrawn from the 
study and appropriate treatment should be administered at the discretion of the investigator.   
6. STUDY PROCEDURES 
6.1. Screening
Subjects will be screened within 42 days prior to administration of the IP to confirm that they 
have met all the subject selection criteria for the study.  The investigator (or an appropriate 
delegate at the investigational site) will obtain informed consent from each subject in 
accordance with the procedures described in Section 12.3 on Subject Information and 
Consent.  At least two visits to the clinical facility will be necessary to complete all screening 
procedures, including colonoscopy.  The colonoscopy should be performed after all other 
eligibility criteria have been met and within 10 days of baseline, preferably 5 to 7 days prior 
to the baseline to allow Mayo score calculation.
Subjects may be re-screened one time at the discretion of the sponsor if they fail their initial 
screening .
Written informed consent must be obtained prior to performance of any protocol specific 
procedures.
The following procedures will be completed:

Informed Consent Document (ICD).

Demography, complete medical history (including UC and smoking).

Review of inclusion and exclusion criteria.

Complete history of steroids, immunosuppressive and/or anti-TNF and anti-integrin 
treatment with no limitation of time prior to signing the ICD.

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).
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
Measurement of height (in or cm) and weight (lbs or kg) without shoes.

Complete physical examination.

Standard 12-lead ECG (see Section 7.2.8 and Schedule of Activities).

Chest x-ray unless a radiograph was performed within 12 weeks prior to study entry 
(screening).  Official reading/report must be located in the source documentation
(see Section 7.2.9 and Schedule of Activities).

Contraception check.

Collect blood, urine and/or stool samples for the following laboratory tests; the 
screening labs may be repeated once if necessary to confirm eligibility:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

HbA1c.

Serum FSH [women of non-childbearing potential (WONCBP) only].

Serum pregnancy test (WOCBP only) (Note: If serum pregnancy test is borderline 
positive, the central lab will run an FSH test as a reflex test).

Serology screens for HBsAg, total HBcAb, HCVAb (confirmed by HCV RNA) 
and HIV (documentation of a negative HIV test result within 12 months of 
screening will be accepted and must be available in source documentation.

TB screening (Mantoux [PPD] or IGRA test per local guidelines [performed at 
local lab where feasible]) unless a negative test result was obtained up to 
12 weeks prior to screening.  Documentation of IGRA official reading and 
method of test must be located in the source documentation.

Stool specimen for enteric pathogens with culture and sensitivity for Clostridium 
difficile (performed locally or at the central laboratory) (see Section 7.2.5 for 
Clostridium difficile).

 

Subjects will be instructed on the use of the e-diary for daily collection of subject 
stool diary data.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).
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
UC Assessment:

Colonoscopy should be performed within approximately 10 days of baseline, 
preferably 5 to 7 days prior to the baseline to allow Mayo score calculation.  The 
endoscopic subscore by the Central Reader must be available at baseline visit.  
The assessment by the Central Reader will be used to derive the Mayo score for 
study eligibility.  The endoscopic report must be available in the source 
documents. 

Total Mayo score based on centrally-read endoscopic subscore, stool frequency
and rectal bleeding (from e-diary) and physician’s global assessment (See 
Section 7.3.3 and Schedule of Activities).
6.2. Study Period
For the study period described below, where multiple procedures are scheduled at the same 
time point(s) relative to dosing, it is recommended that the following chronology of events be 
followed, where possible:

ECGs: obtain prior to vital signs and as close as possible to scheduled time, but prior 
to blood specimen collection.

Sitting BP and pulse rate: obtain as close as possible to scheduled time, but prior to 
blood specimen collection.

PK blood specimens: obtain at scheduled time.

Other procedures: all procedures should be obtained as close as possible to the 
scheduled time, but may be obtained before or after blood specimen collection.

The following order is recommended for post-dosing procedures:

Complete infusion and flush; record time of completion on CRF when flush is 
complete;

Complete PK draw at scheduled time;

Obtain vital signs;

Obtain ECG;
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
Complete any other required procedures and 2 hour post-dose observation period.
6.2.1. Baseline Visit – Week 0/Day 1
The baseline visit must occur on the projected visit date within approximately 42 days of the 
completion of screening procedures.  All baseline procedures and tests must be completed 
prior to administration of the first dose of IP.  Results of the baseline laboratory tests are not 
required for IP administration but must be reviewed as soon as possible thereafter.
Prior to dosing the following procedures will be completed:

Review eligibility criteria to ensure and confirm subject meets entry criteria.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Record subject’s weight.

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

Retained pharmacogenomic sample (Prep D1).

PD Biomarkers: 
, serum total sTL1A, 
 
, hsCRP.

Stool sample for fecal calprotectin.

Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.

Immunogenicity: ADA, NAb, ELISpot, B-cell isolation, ADA epitope/affinity.

UC Assessment:
and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Review stool e-diary completion instructions.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).
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
Review prior and concomitant medications/treatments, including steroids.

Contraception check.
Dosing may occur after all screening procedures are completed and results reviewed.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

12-lead ECG.

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and injection site reactions (ISRs).  Subjects should be 
monitored for a minimum of 2 hours following end of administration of PF-06480605 
infusion. 
6.2.2. Visit 2, Week 2/Day 15 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: 
, serum total sTL1A, 
 
, hsCRP.

Stool sample for fecal calprotectin.

Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.

Immunogenicity: ADA, NAb, ADA epitope/affinity.
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
UC Assessment: 
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.3. Visit 3, Week 4/Day 29 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Pre-dose ECG: ECG should be administered approximately 30 minutes prior to 
dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Record subject’s weight.

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarker: serum total sTL1A, hsCRP.

Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.
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
Immunogenicity: ADA, NAb, ADA epitope/affinity.

UC Assessment: 
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Post dose ECG: ECG should be administered approximately one hour post dose (end 
of infusion).

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.4. Visit 4, Week 6/Day 43 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarker: serum total sTL1A, hsCRP.

Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.
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
Review stool e-diary completion instructions (See Schedule of Activities).

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.5. Visit 5, Week 8/Day 57 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Pre-dose ECG: ECG should be administered approximately 30 minutes prior to 
dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Record subject’s weight.

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: 
, serum total sTL1A, 
 
, hsCRP.

Stool sample for fecal calprotectin and 
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
Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.

Immunogenicity: ADA, NAb, ADA epitope/affinity.

UC Assessment:  
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Post dose ECG: ECG should be administered approximately one hour post dose (end 
of infusion).

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.6. Visit 6, Week 10/Day 71 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarker: Serum total sTL1A, hsCRP.
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
Pre-dose PK:  PK sample should be collected approximately 30 minutes prior to 
dosing.

Review stool e-diary completion instructions (See Schedule of Activities).

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.7. Visit 7, Week 12/Day 85 (3 Days Based on Day 1 Visit)
Prior to dosing the following procedures will be completed:

Pre-dose ECG: ECG should be administered approximately 30 minutes prior to 
dosing.

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately 30 minutes prior to dosing. 

Record subject’s weight.

Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarker: Serum total sTL1A, hsCRP.
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
Stool sample for fecal calprotectin and 

Pre-dose PK: PK sample should be collected approximately 30 minutes prior to 
dosing.

Immunogenicity: ADA, NAb, ELISpot, ADA epitope/affinity.

UC Assessment:
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Contraception check.

Administer PF-06480605 as described in Section 5.4.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Post dose ECG: ECG should be administered approximately one hour post dose (end 
of infusion).

Measure vital signs including sitting BP and pulse (after 5 minutes of rest) and 
temperature (oral, tympanic or axillary).  Vital sign measurement should occur 
approximately one hour post dose (end of infusion).

Post dose PK: PK sample should be collected approximately one hour post dose (at 
end of infusion).

Monitor subject for AEs and ISRs.  Subjects should be monitored for a minimum of 
2 hours following end of administration of PF-06480605 infusion.
6.2.8. Visit 8, Week 14/Day 99 (3 Days Based on Day 1 Visit)

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).

Complete physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: hsCRP, 
, serum total 
sTL1A, 
, 
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
PK.

Immunogenicity: B-cell isolation.

UC Assessment:

Colonoscopy: The endoscopic report and pathology report must be available in 
the source documents. 

Total Mayo score based on centrally-read endoscopic subscore, stool frequency 
rectal bleeding and physician’s global assessment (See Section 7.3.3 and 
Schedule of Activities).


Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.

Contraception check.
6.2.9. Visit 9, Week 16/Day 113 (7 Days Based on Day 1 Visit)

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).

Record subject’s weight.

Targeted physical examination.

12-Lead ECG.

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: hsCRP, serum total sTL1A.

PK.
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
Immunogenicity: ADA, NAb, ADA epitope/affinity.

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.

Contraception check.
6.2.10. Visit 10, Week 20/Day 141 (7 Days Based on Day 1 Visit)

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).

Record subject’s weight.

Targeted physical examination.

12-Lead ECG.

UC Assessment: 
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: hsCRP, serum total sTL1A.

PK.

Immunogenicity: ADA, NAb, ELISpot, ADA epitope/affinity.

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.

Contraception check.
6.2.11. Visit 11, Week 24/Day 169 (7 Days Based on Day 1 Visit)

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).
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
Targeted physical examination.

Collect blood, urine and/or stool samples for the following laboratory tests:

Urine pregnancy test (WOCBP only).

PD Biomarkers: hsCRP, serum total sTL1A.

PK.

Immunogenicity: ADA, NAb, ADA epitope/affinity.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Review stool e-diary completion instructions (See Schedule of Activities).

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.

Contraception check.
6.2.12. Final On-Site Study Visit: Visit 12, Week 26/Day 183 (7 Days Based on Day 1 
Visit)

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).

Record subject’s weight.

Complete physical examination.

12-Lead ECG.

UC Assessment: 
 and review subject stool e-diary data (See 
Section 7.3.5 and Schedule of Activities).

Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).

PD Biomarkers: hsCRP, serum total sTL1A.

Stool sample for fecal calprotectin and 
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
PK.

Immunogenicity: ADA, NAb, ELISpot, ADA epitope/affinity.

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.  Subjects with AEs as a result of positive ADA/NAbs may 
be requested to return for additional follow-up for up to 3 months after the final on 
site study visit and will have PK samples collected in addition to ADA/NAb samples.  
Other assessments may also be performed during these visits as appropriate 
depending upon the actual AE that is experienced.

Contraception check.
6.3. Subject Withdrawal
Any subject who prematurely withdraws during active treatment (Week 0 through Week 12) 
should return for an early withdrawal visit and then enter the follow up period.  The 
following procedures will be performed at the early withdrawal visit:

Vital signs measurements including sitting blood pressure (BP) and pulse (after 
5 minutes of rest) and temperature (oral, tympanic or axillary).

Record subject’s weight.

Complete physical examination.

12-Lead ECG.

UC Assessment:

Colonoscopy: The endoscopic report and pathology report must be available in 
the source documents. 

Total Mayo score based on centrally-read endoscopic subscore, stool frequency 
rectal bleeding and physician’s global assessment (See Section 7.3.3 and 
Schedule of Activities).



Collect blood, urine and/or stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis.

Urine pregnancy test (WOCBP only).
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
PD Biomarkers: hsCRP, 
, serum total 
sTL1A,
.

Stool sample for fecal calprotectin and 

PK.

Immunogenicity: ADA, NAb, ELISpot, B-cell isolation, ADA epitope/affinity.

Review prior and concomitant medications/treatments, including steroids.

Monitor subject for AEs.

Contraception check.

End of study CRF.
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return for a final visit, if applicable, 
and follow up with the subject regarding any unresolved AEs.
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely fashion.
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7.1. Blood Volume
Total planned blood sampling for an individual subject that completes all currently scheduled 
assessments through the Week 26 visit is approximately 613 mL.  Additional blood samples 
may need to be collected at times not specified in the protocol (eg, replacement of clotted or 
compromised specimens or repeat of clinically significant out of range laboratory results).
7.2. Safety
7.2.1. Laboratory
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities.
Laboratory Tests
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
HbA1ce
FSHd,e
-hCGf
Hepatitis B, C and HIVe
QFT-G or other IGRAe
hsCRP
Stool samplee to detect 
enteric infections and C. 
difficile toxins A and B
Stool sample for fecal 
calprotectin
ADAs
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. In females who are amenorrheic for at least 12 consecutive months. 
e.  Complete at screening.
f.  If serum pregnancy test is borderline positive, the central lab will run a FSH test to confirm menopause.
7.2.2. Pregnancy Testing
For female subjects of childbearing potential, a serum or urine pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed at screening, before IP administration at 
the baseline visit, and at the end of treatment visit.  A negative pregnancy result is required 
before the subject may receive the IP.  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 repeated at all visits and at the end of the study to confirm the 
subject has not become pregnant during the study. Pregnancy tests may also be repeated as 
per request of IRBs/IECs or if required by local regulations. 
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In the case of a positive confirmed pregnancy, the subject will be withdrawn from 
administration of IP but may remain in the study in follow up. 
7.2.3. Purified Protein Derivative (PPD) Tuberculin Test
Subjects may be screened for TB using the PPD Tuberculin Test per local guidelines.  The 
test consists of intracutaneous injection of 5 Tuberculin Units (5 TU) PPD in 0.1 mL of 
solution on the volar aspect of the forearm, using a short beveled 26- or 27- gauge needle 
(Mantoux test).  After the tuberculin test is administered, the test area will be evaluated by a 
qualified healthcare professional, per local guidelines, 48 to 72 hours later to determine if the 
test is positive or negative.  The test is positive if the induration diameter is 25 mm at 48 to 
72 hours post injection.
To be eligible for this study, a negative test response is required during screening unless the 
test was performed and documented negative within 12 weeks prior to screening.  Subjects 
with suspected false positive PPD results, eg, results from suspected BCG vaccination, 
should be further tested with an Interferon Gamma Release Assay (IGRA) assay during 
screening. 
7.2.4. Interferon Gamma Release Assay Tuberculin Test
Subjects may be screened for TB using an IGRA per local guidelines.  IGRA will be tested 
locally where feasible during screening or within 12 weeks prior to screening.  The following 
are acceptable assays:  QuantiFERON-TB Gold test (QFT-G), QuantiFERON-TB Gold 
In-Tube test (QFT-GIT) and T-SPOTTB test.  Blood sampling may include 3 mL up to 
10 mL of blood.  Site personnel should follow the processing and analyses steps based on the 
assay chosen.  Ensure incubation steps are followed as appropriate. 
The sample(s) will be analyzed by the site’s local laboratory where feasible.  Refer to local 
lab for any additional processing information and shipping instructions.
7.2.5. Screening for Clostridium Difficile
Highly sensitive screening tests, with high negative predictive value, should be employed in 
evaluating subjects for eligibility for the study.  The detection of C. difficile by toxigenic 
stool culture [stool culture followed by detection of toxin] is considered the gold standard for 
the diagnosis of the colonization or infection with pathogenic C. difficile.  Comparable 
sensitivity may be achieved by direct testing of stool via point of use rapid membrane 
enzyme immunoassay card for both C. difficile toxin A and B and glutamate dehydrogenase 
(GDH) antigen on a card.  Use of the card for point of care screening is encouraged where 
permitted by local regulation.  Molecular techniques such as polymerase chain reaction 
(PCR) for detection of toxin RNA are also acceptable alternatives. 
Refer to the lab manual for further guidance and instruction for C. difficile screening.
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7.2.6. Vital Signs (Blood Pressure, Pulse Rate, and Temperature)
Single sitting BP, pulse rate, and temperature will be measured at times specified in the 
Schedule of Activities.  Additional collection times or changes to collection times will be 
permitted, as necessary to ensure appropriate collection of safety data.
Sitting blood pressure will be measured with the subject’s arm supported at the level of the 
heart, and recorded to the nearest mm Hg.  It is preferred that the same arm (preferably the 
dominant arm) be used throughout the study.
The same size BP cuff, which has been properly sized and calibrated, will be used to measure 
BP each time.  The use of automated devices for measuring BP and pulse rate are acceptable, 
although, when done manually, pulse rate will be measured in the brachial/radial artery for at 
least 30 seconds.  When the timing of these measurements coincides with a blood collection, 
it is preferred that vital signs be obtained prior to the nominal time of blood collection.
It is preferred that body temperature be collected using tympanic, oral, or axillary methods 
and that the same method be used consistently throughout the study.
7.2.7. Medical History, Physical Examination, Height and Weight
Medical history (including UC and smoking history) will be collected at the Screening visit.
Complete physical examinations must be performed by the investigator, sub-investigator, or 
a qualified healthcare professional per local guidelines.  Complete physical examinations 
consist of 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.
Targeted physical examinations must be performed by the investigator, sub-investigator, or a 
qualified healthcare professional per local guidelines and should include skin, heart, lungs, 
abdomen and examination of body systems where there are symptom complaints by the 
subject. 
Complete and Targeted physical examinations are performed at specified timepoints (See 
Schedule of Activities).
Height and weight will be measured without the subject wearing shoes.  Height (inches or 
centimeters) will be measured and recorded at the Screening visit only and weight (lbs or kg) 
will be measured and recorded at various timepoints (See Schedule of Activities).
7.2.8. Electrocardiogram (ECG)
Twelve (12) lead ECGs should be collected at times specified in the Schedule of Activities.
All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position.  When the timing of these measurements coincides with a 
blood collection, the ECG should be obtained prior to the nominal time of the blood 
collection, BP, and pulse rate.
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To ensure safety of the subjects, a qualified individual (eg, sub-investigator) at the 
investigator site will make comparisons to baseline measurements taken at screening.  A 
copy of the ECG should be available as source documents for review.  ECGs will be read 
locally during the dosing period.  However, all ECGs will be interpreted by a central reader.  
Pfizer and the central ECG vendor will provide sites with the instructions and supplies for 
processing.
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 are placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc 
value is prolonged, repeat measurements may not be necessary if a qualified physician’s 
interpretation determines that the QTc values are in the acceptable range. 
7.2.9. Chest Radiograph
Chest X-ray (posterior-anterior and lateral views are recommended however local guidelines 
should be followed) with no evidence of current, active TB or previous inactive TB, general 
infections, heart failure or malignancy taken at screening or within the 12 weeks prior to 
screening and read by a qualified radiologist.  Documentation of the official reading must be 
located and available in the source documentation.
7.3. Diagnostic and Efficacy Assessments
7.3.1. Colonoscopy
Colonoscopy should be performed within 10 days of baseline, preferably 5 to 7 days prior to 
the baseline to allow total Mayo score calculation.  The endoscopic subscore by the Central 
Reader must be available at 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. 
A colonoscopy is also performed at Visit 8 (Week 14) or at the early withdrawal visit where 
applicable.  Bowel preparation should be conducted as per local routine.  The position of the 
endoscope at the Visit 8 or early withdrawal visit will be based on the length of the 
instrument at various levels of insertion as well as the morphological features of the intestine 
as seen during screening colonoscopy.  The colonoscopy report and any photographs and/or 
video recordings taken during the procedure per local custom should be filed in the subject’s 
chart.  The findings of the colonoscopy component should be completed at the end of the 
procedure to document the endoscopic subscore.
7.3.2. Biopsy Collection from Colonic Mucosa 
Biopsies will be collected at Screening and Week 14 and early withdrawal visit.  The largest 
standard forceps should be used to obtain biopsies during each colonoscopy procedure.  
Biopsies should be taken one at a time, and each should be immediately placed into a 
separate sample collection tube, as specified in the central vendor procedure manual.  During 
each colonoscopy procedure, 12-15 biopsies should be taken from abnormally inflamed 
colonic mucosa, and 3 biopsies should be taken from normal appearing mucosa, resulting in a 
total of 15-18 biopsies from each subject, if possible.  Frankly ulcerated areas should be 
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avoided.  If 15-18 biopsies cannot be collected during colonoscopy, then samples from 
inflamed tissues should be prioritized. Pfizer and the central laboratory vendor will provide 
sites with instructions for the collection, processing, and shipment of biopsy samples.
All pre-treatment biopsies should be obtained in a targeted manner from the most affected 
area 15-30 cm from the anal verge.  During post-treatment colonoscopy, samples should be 
obtained from approximately the same anatomic location as the baseline assessment.  For all 
biopsies collected, record the colonic segment and approximate distance from the anal verge 
for each sample in the source documents.  
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7.3.3. Mayo Score
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 2).

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 subject’s stool frequency and 
any amount of blood in the stool.  The Mayo scores will be calculated based on the subject’s 
stool e-diary data recorded over the 3 consecutive days prior to the endoscopy bowel 
preparation procedure. Investigator sites will be trained on the electronic diary usage and 
will train subjects on use of the e-Diary.  Electronic diary data entered by the subject will be 
reviewed by the site at each visit.  
For baseline endoscopy and post-baseline endoscopy, if there are missing e-diary data, the 
average will be taken from the 3 most recently available days reported within 5 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 3 available days reported within the 5 days prior to the study visit, the 
average will be taken from the limited available data unless there is no diary data reported 
within 5 days. In this case, stool frequency and rectal bleeding subscores will be considered 
as missing.
The endoscopic appearance will be read by the Central Reader.
The physician’s global assessment (PGA) acknowledges the other three criteria, the subject’s 
abdominal discomfort and sense of general well-being.  In addition, the investigator should 
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consider other observations (ie, physical findings) and subject’s performance status when 
making the PGA assessment.  It is preferred that the same physician performs all such 
assessments for a given subject throughout the study.
The Mayo Score at the screening visit must be 6 and 12 with an endoscopic subscore of at 
least 2 and meet all other eligibility criteria to be eligible for the study.  The duration of the 
time between the Mayo endoscopic subscore assessment and baseline should not exceed 
10 days.
7.3.4. Subject Stool Diary
Subjects will use an e-diary in order to record on a daily basis the following information 
during the study:

‘Normal’ number of stools per day (when not having a flare).  This question will be 
asked only at the screening visit. 

Number of times needed to visit the toilet to have a bowel movement (per day).

Presence of blood in the stools (if any).

Description of blood in the stools (if any).
Diary data will be assessed at the clinic, at each study visit from baseline (Day 1) until the 
end of follow up period (Week 26).  The information extracted will be used for calculation of 
Mayo score taking into account the data recorded over the last 3 days prior to each study 
visit.  Three (3) 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 3 most 
recently available days reported within 5 days prior to the endoscopy preparation.  If there 
are less than 3 available days reported within the 5 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 
5 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.
In order to encourage consistent diary recording, subjects should enter diary data 
continuously throughout the study.  Instructions for completing the e-diary will be provided 
to subjects at screening and reviewed at subsequent visits.
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7.4. Pharmacodynamics 
7.4.2. Serum Soluble TL1A
Blood samples (6 mL) to provide approximately 3 mL serum will be collected into 
appropriately labeled glass collection tubes (no additives).  Serum samples will be collected 
and aliquoted for the analysis of total serum sTL1A at times specified in the Schedule of 
Activities. 
Detailed collection, processing, storage, and shipment instructions are provided in the lab 
manual.
7.4.4. High-Sensitivity C-Reactive Protein (hsCRP)
A blood specimen for determination of hsCRP will be obtained at the times specified in the 
Schedule of Activities.  Blood samples for determination of hsCRP will be analyzed at the 
same laboratory performing the safety laboratory analyses. 
7.4.5. Fecal Calprotectin
A stool sample for determination of fecal calprotectin will be obtained at the times specified 
in the Schedule of Activities.
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The study site personnel will provide appropriately labeled containers and instructions to the
subject on how best to collect a sufficient fecal sample.  A sample collected on the day of the 
visit is preferred, however if this is not possible, a sample from the day before or day after 
the visit should be collected. 
Instructions and supplies for the collection, processing and shipment of samples will be 
supplied under separate cover by Pfizer, the designated laboratory vendor, and the vendor 
laboratory manual. 
7.5. Pharmacokinetics
7.5.1. Serum for Analysis of PF-06480605
Blood samples (3 mL) to provide approximately 1.2 mL serum for PK analysis will be 
collected into appropriately labeled tubes at times specified in the Schedule of Activities.
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.  
However, samples obtained within 10 % of the nominal time from dosing will not be 
captured as a protocol deviation, as long as the exact time of the sample collection is noted 
on the source document and data collection tool (eg, CRF).
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.
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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.  
 
  Samples collected for 
this purpose will be retained in accordance with local regulations and, if not used within this 
timeframe, will be destroyed.
7.5.2. Shipment of Serum Samples for Analysis of PF-06480605
The shipment address and contact information for the lab will be provided to the Investigator 
site prior to initiation of the trial.
7.6. Immunogenicity
7.6.1. Serum for Analysis of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies
Blood samples (3 mL) to provide approximately 1.2 mL serum 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 Schedule of Activities. 
A tiered ADA testing strategy will be used: all samples that are positive at baseline will be 
confirmed for antibody specificity.  Confirmed positive samples will be further characterized 
for titer and tested in the NAb assay, if bioanalytically feasible. 
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. 
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. 
 
 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. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the IP will be reported as described in the following sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a SAE
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE.  The investigator is required to assess causality.  Follow-up by the investigator may be 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving IP, through and including 28 calendar days after the last administration of the IP.  
SAEs occurring to a subject after the active reporting period has ended should be reported to 
the sponsor 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 IP are to be 
reported to the sponsor.
AEs (serious and non-serious) should be recorded on the CRF from the time the subject has 
taken at least 1 dose of IP through the subject’s last visit.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to: 

Abnormal test findings;

Clinically significant symptoms and signs;
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
Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF, which is a specific version of the AE page, and on the SAE form when 
appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the IP;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page 
and, if applicable, any associated AE(s) are captured on an AE CRF page.
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
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8.6.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study. All SAEs will be reported by the 
investigator as described in previous sections, and will be handled as SAEs in the safety 
database (see the section on Serious Adverse Event Reporting Requirements).
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events. 
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions.  Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (× ULN) concurrent with a total bilirubin value 2 × ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 × ULN or not available;

For subjects with preexisting ALT OR AST OR total bilirubin values above the 
ULN, the following threshold values should be used in the definition mentioned 
above:

For subjects with 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).
Concurrent with

For subjects with preexisting values of total bilirubin above the normal range: 
Total bilirubin level increased from baseline by an amount of at least 1 × ULN or
if the value reaches 3 × ULN (whichever is smaller).
The subject should return to the investigational 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, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl 
transferase, prothrombin time (PT)/international normalized ratio (INR), and alkaline 
phosphatase.  A detailed history, including relevant information, such as review of ethanol, 
acetaminophen, recreational drug, and supplement consumption, family history, occupational 
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exposure, sexual history, travel history, history of contact with a jaundiced person, surgery, 
blood transfusion, history of liver or allergic disease, and work exposure, should be collected.  
Further testing for acute hepatitis A, B, or C infection and liver imaging (eg, biliary tract) 
may be warranted.  All cases confirmed on repeat testing as meeting the laboratory criteria 
defined above, with no other cause for liver function test (LFT) abnormalities identified at 
the time, should be considered potential Hy’s law cases irrespective of availability of all the 
results of the investigations performed to determine etiology of the abnormal LFTs.  Such 
potential Hy’s law cases should be reported as SAEs.
8.7. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a TB
unit).  An emergency room visit does not necessarily constitute a hospitalization; however, 
the event leading to the emergency room visit should be assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of persistent pretreatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);
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
Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.8. Severity Assessment
If required on the AE CRFs, the investigator will use the adjectives MILD, MODERATE, 
or SEVERE to describe the maximum intensity of the AE.  For purposes of consistency, 
these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the IP caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the IP caused the event, then the event will be 
handled as “related to IP” for reporting purposes, as defined by the sponsor (see the section 
on Reporting Requirements).  If the investigator's causality assessment is "unknown but not 
related to IP," this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
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8.10. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:
1. 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 IP; or the female 
becomes or is found to be pregnant after discontinuing and/or being exposed to the 
IP.
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).
2. A male has been exposed (eg, because of treatment or environmental exposure) to the 
IP prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy.
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the IP, the investigator must submit this information to the 
Pfizer drug safety unit on an 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 subject 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) 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 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 preprocedure 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 as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;
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
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 IP.
Additional information regarding the EDP may be requested by the investigator.  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 study subject with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.11. 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 the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file.
8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page. 
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.13. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject /legally acceptable representative.  In addition, each study subject /legally 
acceptable representative will be questioned about AEs.
8.14. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.14.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.
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In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Nonserious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a statistical analysis plan (SAP), which will be maintained by the 
sponsor.  This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
9.1. Statistical Methods
This study employs Simon’s two-stage design.  Let p be the proportion of subjects achieving 
endoscopic improvement at Week 14 and the following hypotheses will be tested in this 
study:
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H0: p 6% versus H1: p 41%, 
where 6% was the observed placebo endoscopic improvement rate in anti-TNF experienced 
subjects from two tofacitinib Phase 3 induction studies (A3921094 and A3921095) in 
subjects with UC.  In the first stage, it is planned to have 12 evaluable subjects with 
colonoscopy at Week 14.  If no more than 2 subjects have achieved endoscopic improvement
AND no subject has achieved endoscopic remission, then the study will be stopped for 
futility; otherwise, the study will continue to enroll until 36 evaluable subjects complete the 
study with colonoscopy at Week 14.  If at least 9 subjects achieve endoscopic improvement
at Week 14 at the end of the second stage, the null hypothesis H0 will be rejected.
9.2. Sample Size Determination
The sample size was determined based on the primary endpoint of endoscopic improvement
at Week 14 using Simon’s two-stage design.  The operating characteristics of the design 
described in Section 9.1 were assessed through Monte Carlo simulations.  With 12 evaluable 
subjects in the first stage and a maximum total of 36 evaluable subjects and the H0 rejection 
criterion described in Section 9.1, the Simon’s two-stage design has at least 90% power 
under the alternative hypothesis H1 while the type-I error is less than 0.001.  On the other 
hand, the probability of stopping early for futility in the first stage is at least 86% under the 
null hypothesis H0 and an endoscopic remission rate of 1%.
9.3. Efficacy Analysis
9.3.1. Analysis of the Primary Endpoint 
The primary efficacy endpoint, endoscopic improvement at Week 14, will be used to assess 
the efficacy of PF-06480605 under Simon’s two-stage design decision criteria.  The primary 
analysis population will be Per Protocol population, which consists of all subjects who are 
not major protocol violators with all planned doses received and a final colonoscopy at 
Week 14.  The point estimate of the endoscopic improvement rate, 2-sided 95% confidence 
interval and p-value will be calculated using the method described by Koyama and Chen 
(2008)11 according to the actual sample size in the primary analysis population.  Details of 
the methodology will be documented in the SAP. 
The endoscopic improvement rate at Week 14 for All Treated population will also be 
computed with appropriate confidence interval as a sensitivity analysis.  Subjects who drop 
out early from the study without a Week 14 colonoscopy will be considered as failures in the 
sensitivity analysis.
9.3.2. Analysis of Secondary Endpoint
The binary secondary efficacy endpoints, including remission and endoscopic remission at 
Week 14, as defined in Section 2.2.2, will be summarized by point estimates and appropriate 
confidence intervals.  These endpoints will be analyzed separately for All Treated population 
and Per Protocol population.  Subjects who drop out early from the study without a Week 14 
colonoscopy will be considered as failures in the All Treated population analysis. 
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9.4. Analysis of Other Endpoints
9.4.1. Pharmacokinetic Analysis
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06480605 and in whom at least one concentration value is reported.
PK concentrations will be summarized and presented with summary statistics and, if
appropriate, non-compartmental PK parameter estimates will be provided.  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 subjects 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. 
An early PK readout of PF-06480605 serum concentrations will be conducted after at least 
6 subjects have completed the Week 4 visit to confirm that the predicted exposures of 
PF-06480605 in UC patients are consistent with expected values, based on the healthy 
subject PK data.  Following this early PK readout analysis, dose may be modified to match 
the exposures observed in healthy volunteers receiving 500 mg/kg IV (Study B7541001). 
9.4.2. Immunogenicity Analysis
The immunogenicity assessment population is defined as all enrolled subjects who received 
at least one dose of PF-06480605 with at least one post-treatment anti-drug (PF-06480605) 
antibody determination.
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.
 
CCI
CCI
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9.4.4. Pharmacodynamic Analysis
The pharmacodynamic analysis population is defined as all treated subjects who have at least 
one PD assessment.  The PD endpoints will be summarized by time and presented in a 
tabular or graphical form.  Data permitting, the endpoints may be analyzed longitudinally to 
study the effect over time.  Further details will be documented in the SAP.
9.5. Safety Analysis
All clinical AEs, SAEs, TEAEs, withdrawal due to AEs, ECGs, vital signs and safety 
laboratory data will be reviewed and summarized on an ongoing basis during the study to 
evaluate the safety of subjects. 
The safety analysis set will include all subjects who have received at least one dose of IP.  
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.  All safety endpoints will be listed and summarized in 
accordance with Pfizer Data Standards.  Categorical outcomes (eg, AEs) will be summarized 
by subject counts and percentage.  Continuous outcome (eg, BP, heart rate, etc) will be 
summarized using N, mean, median, standard deviation, etc.  Change from baseline in 
laboratory data, ECGs and vital signs will also be summarized.  Subject listings will be 
produced for these safety endpoints accordingly. 
9.5.1. Electrocardiogram Analysis
Descriptive statistics for RR, QRS, QTcF, and HR, and change from baseline in those 
parameters will be summarized by timepoint. Baseline will be defined as the ECG 
measurements at the screening visit.  The number (%) of subjects with maximum post dose 
QTcF values and maximum increases from baseline in the following categories will be 
tabulated: 
Safety QTcF
Borderline (msec)
Prolonged (msec)
Absolute Value
450 - <480
480
Absolute Change
30-<60
60
In addition, the number of subjects with corrected and uncorrected QT values 500 msec will 
be summarized.
9.6. Interim Analysis 
A formal IA is planned at the end of the first stage for futility assessment.  The IA will be 
performed by the study team.  The results and decision of the IA will be reviewed and 
endorsed by sponsor senior management.  The sponsor may conduct ongoing reviews of the 
data during the course of the study for the purpose of safety assessment, facilitating PK/PD 
modeling, and/or to support clinical development.
9.7. Data Monitoring Committee 
This study will not use a data monitoring committee.
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10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
During study conduct and/or after study completion, the study site may be subject to review 
by the institutional review board (IRB)/ethics committee (EC), and/or to quality assurance 
audits performed by Pfizer, or companies working with or on behalf of Pfizer, and/or to 
inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the study site for the inspection and will allow Pfizer or its agent, 
whenever feasible, to be present during the inspection.  The investigator will promptly 
provide copies of the inspection findings to Pfizer or its agent.  Before response submission 
to the regulatory authorities, the investigator will provide Pfizer or its agents with an 
opportunity to review and comment on responses to any such findings.
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.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
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In most cases, the source documents are the hospital's or the physician's subject chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigative site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to the ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
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Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association (1996 & 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by a numerical code based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The study site 
will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed and approved by the sponsor, approved by the IRB/EC before use, and available for 
inspection.
The investigator must ensure that each study subject or his or her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. 
Whenever consent is obtained from a subject’s legally acceptable representative, the 
subject’s assent (affirmative agreement) must subsequently be obtained when the subject has 
the capacity to provide assent, as determined by the IRB/EC.  If the investigator determines 
that a subject’s decisional capacity is so limited he/she cannot reasonably be consulted, then, 
as permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
subject’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study subject does not provide his or her own consent, the source documents
must record why the subject did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the subject’s legally 
acceptable representative, the consent signer’s relationship to the study subject (eg, parent, 
spouse), and that the subject’s assent was obtained, or waived.  If assent is obtained verbally 
it must be documented in the source documents.
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The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legally acceptable representative, before any 
study-specific activity is performed. The investigator will retain the original of each subject's 
signed consent document.
12.4. Subject Recruitment
Advertisements approved by IRBs/ECs and investigator databases may be used as 
recruitment procedures.
Pfizer will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used. 
12.5. 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 
competent 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 IP, Pfizer 
should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV). 
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or IP safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of PF-06480605 at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within 28 days.  As directed by Pfizer, all study
materials must be collected and all CRFs completed to the greatest extent possible.
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15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial 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 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.
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 Pfizer 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are submitted for posting within 1 year of the primary completion date for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations.
Primary completion date is defined as the date that the final subject 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 primary completion date for studies in adult populations or 
within 6 months of the primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has 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.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product.  
However, to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
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publication or other type of disclosure of the results of the study (collectively, “Publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before they are 
submitted for publication or otherwise disclosed. If any patent action is required to protect 
intellectual property rights, the investigator agrees to delay the disclosure for a period not to 
exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all study sites, and that any subsequent publications by the 
principal investigator will reference that primary publication. However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
study at all participating sites, the investigator is free to publish separately, subject to the 
other requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.
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16. REFERENCES
1.
Bamias et al, 2003; Prehn et al, 2004; Yamazakl et al, 2005; Bamias et al, 2006; Barrett 
et al, 2008; Takedatsu et al, 2008; Kakuta et al, 2009; Shih et al, 2009; Kamada et al, 
2010; Meylan et al, 2011; Taraban et al, 2011; Jostins et al, 2012; Yamazaki et al, 2013; 
Shih et al, 2014. 
2.
Molodecky NA, Soon IS, Rabi DM, et al.  Increasing incidence and prevalence of the 
inflammatory bowel diseases with time, based on systematic review.  Gastroenterology. 
Jan 2012;142(1):46-54 e42;quize30.
3.
Betteridge JD, Armbruster SP, Maydonovitch C, Veerappan GR. Inflammatory bowel 
disease prevalence by age, gender, race, and geographic location in the U.S. military 
healthcare population. InflammBowelDis. Jun2013;19(7):1421-1427.
4.
Le, TH, Ulcerative Colitis [http://emedicine, Medscape Web site]. June 28, 2010. 
Available at http://emedicine.medscape.com/article/183084- overview.
5.
Rutgeerts P1, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, 
Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, 
Colombel JF.Infliximab for induction and maintenance therapy for ulcerative colitis. N 
Engl J Med. 2005 Dec 8;353(23):2462-76.
6.
ULTRA-1 Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction 
of clinical remission in moderately to severely active ulcerative colitis: results of a 
randomised controlled trial. Gut. 2011;60:780–787. ULTRA-2 Sandborn WJ, van 
Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in 
patients with moderate-to-severe ulcerative colitis. Gastroenterology. 
2012;142:257-265-e13.
7.
Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van 
Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, 
Parikh A. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N
Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734. GEMINI 1 
Study Group.
8.
Bugelski PJ, Treacy G.  Predictive power of preclinical studies in animals for the 
immunogenicity of recombinant therapeutic proteins in humans.  Curr Opin Mol Ther 
2004 Feb;6(1):10-6.
9.
Gibiansky L and Gibiansky E  Expert Opin Drug Metab Toxicol. 2009 Jul;5(7):803-12.
10.
Dirks NL and Meibohm B Clin. Pharmacokinetics, 2010; 49 (10):633-659.
11.
Koyama T. and Chen H. Proper inference from Simon’s two-stage designs. Stat Med. 
2008 July; 27(16):3145-54.
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12.
Mosli, MH, Feagan BG, Zou G, Sandborn WJ, D’haens G, Khanna R, et al. 
Development and validation of a histological index for UC. Gut [Internet]. 2015Oct16 
[cited 2016Apr28]; Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26475633.
13.
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, 
et al. Second symposium on the definition and management of anaphylaxis: Summary 
report-Second National Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium. Journal of Allergy and Clinical Immunology. 
2006;117(2):391-7.  
14.
Common terminology criteria for adverse events (CTCAE). Bethesda, MD: U.S. Dept. 
of Health and Human Services, National Institutes of Health, National Cancer Institute; 
2009. Version 4.03, Publish Date: 14-June-2010, 
http://ctep.cancer.gov/reporting/ctc.html).
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Appendix 1. Abbreviations 
This is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
ADA
Anti-drug antibody
AE
adverse event
ALT
alanine aminotransferase
ANC
Absolute neutrophil count
5-ASA
5-aminosalicylic acid
AST
aspartate aminotransferase
AUC
Area under the curve
AUCinf
Area under the concentration-time curve from time 0 to infinity
AUCss
Area under the curve at steady state
AUCτ
Area under the curve over the dosing interval 
AZA
azathioprine
BCG
Bacillus Calmette-Guerin
BP
Blood pressure
Cav
Average concentration for the dosing interval
CD
Crohn’s disease
Cmax
Maximum observed concentration
CL
clearance
CL/F
Apparent clearance
CRA
Cytokine release assay
CRF
case report form
CSA
clinical study agreement
CTA
clinical trial application
CTCAE
Common Terminology Criteria for Adverse Events
DAI
dosage and administration instructions
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DR3
Death receptor 3
DcR3
Decoy Receptor 3
EC
ethics committee
ECG
electrocardiogram
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
EOS
End of study
EudraCT
European Clinical Trials Database
F
bioavailability
FIH
First-in-human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GDH
Glutamate dehydrogenase
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Abbreviation
Term
GLP
Good laboratory practice
HCV
Hepatitis C virus
HEENT
Head eyes ears nose throat
HIV
human immunodeficiency virus
hsCRP
High sensitivity c-reactive protein
IA
Interim analysis
IB
investigator’s brochure
IBD
Inflammatory bowel disease
ICH
International Conference on Harmonisation
ID
identification
IGRA
Interferon gamma release assay
IM
intramuscular
IND
investigational new drug application
INR
international normalized ratio
IP
Investigational product
IRB
institutional review board
IRT
Interactive response technology
ISR
Injection site reaction
IUD
intrauterine device
IV
intravenous
LFT
liver function test
LSLV
last subject last visit 
MAD
Multiple ascending dose
msec
milliseconds
MTX
methotrexate
N/A
not applicable
NAb
Neutralizing antibody
NOAEL
No observed adverse effect level
P90
percentage of simulations that resulted in 90% coverage 
PBMC
Peripheral blood mononuclear cells
PD
pharmacodynamic
pEFD
Preliminary embryofetal and developmental
PGA
Physician’s global assessment
PK
pharmacokinetic
PPD
Purified protein derivative
PT
prothrombin time
Rac
Observed accumulation ratio
RBC
Red blood cell
RDW
Red blood cell distribution width
RHI
Robarts Histopathology Index
RNA
ribonucleic acid
SAD
Single ascending dose
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Abbreviation
Term
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SCL
Supply Chain Lead
SoA
Site of action
SOP
standard operating procedure
SRSD
single reference safety document
SSID
Single subject identifier
TB
tuberculosis
sTL1A
Soluble TL1A
T1/2
Terminal half-life
TEAE
Treatment emergent adverse event
TL1A
Tumor necrosis factor-like ligand 1A
Tmax
Time to reach maximum concentration
TMDD
Targeted mediated drug disposition
TNF
Tumor necrosis factor
TPMT
Thiopurine methytransferase
UC
Ulcerative colitis
ULN
upper limit of normal
US
United States
Vss
Volume of distribution at steady state
VZ/F
Apparent volume of distribution
WBC
White blood cells
WOCBP
Women of childbearing potential
WONCBP
Women of non child bearing potential
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Appendix 2. Mayo Scoring System for Assessment of Ulcerative Colitis Activity
The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease.  
Data are from Schroeder et al.
Stool frequency†:
0 = Normal no. of stools for this subject
1 = 1 to 2 stools more than normal
2 = 3 to 4 stools more than normal
3 = 5 or more stools more than normal
Subscore, 0 to 3
Rectal bleeding‡:
0 = No blood seen
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passes
Subscore, 0 to 3
Findings on endoscopy:
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern, mild friability)
2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Subscore, 0 to 3
Physician’s global assessment§:
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
Subscore, 0 to 3
†
Each subject serves as his or her own control to establish the degree of abnormality of the stool frequency.
‡
The daily bleeding score represents the most severe bleeding of the day.
§
The physician’s global assessment acknowledges the three other criteria, the subject’s daily recollection of 
abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and 
the subject’s performance status.
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Appendix 3. France appendix
This appendix applies to study sites located in France.
1. GCP Training
Prior to enrollment of any subjects, the investigator and any sub-investigators will complete 
the Pfizer-provided Good Clinical Practice training course (“Pfizer GCP Training”) or 
training deemed equivalent by Pfizer.  Any investigators who later join the study will 
complete the Pfizer GCP Training or equivalent before performing study-related duties.  For 
studies of applicable duration, the investigator and sub-investigators will complete Pfizer 
GCP Training or equivalent every three years during the term of the study, or more often if 
there are significant changes to the ICH GCP guidelines or course materials.
2. Investigational Product
No subjects or third-party payers will be charged for investigational product.
3. Inspections
The study site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the subject's medical records.  
4. Studies Involving Human Cell, Tissue, and/or Organ Transplants
The investigator agrees to abide by the ethical principles set forth in the World Health 
Organization’s Guiding Principles for Human Cell, Tissue and Organ Transplantation 
(WHA63.22), http://www.who.int/transplantation/en/ with regard to the study.
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SAP_001.pdf: 
Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 
 
Protocol B7541002 
 
 
A PHASE 2A, MULTICENTER, SINGLE ARM, OPEN-LABEL, TWO-STAGE, STUDY TO 
EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS 
OF PF-06480605 IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE 
COLITIS 
 
 
 
Statistical Analysis Plan  
(SAP) 
 
 
 
Version: 
2 
Author:          
    (
) 
Date:  
30-Jan-2017 
 
 
 
 
Page 1 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
TABLE OF CONTENTS  
LIST OF TABLES ...........................................................................................................................3 
1. VERSION HISTORY ..................................................................................................................4 
2. INTRODUCTION .......................................................................................................................4 
2.1. Study Objectives .............................................................................................................4 
 Primary Objectives .............................................................................................4 
2.1.1.
 Secondary Objectives .........................................................................................5 
2.1.2.
 
2.2. Study Design ...................................................................................................................6 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ...................................................................................................................6 
3.1. Primary Endpoint(s) ........................................................................................................6 
3.2. Secondary Endpoint(s) ....................................................................................................6 
 
3.4. Baseline Variables ...........................................................................................................8 
4. ANALYSIS SETS .......................................................................................................................8 
4.1. Full Analysis Set .............................................................................................................8 
4.2. Per Protocol Analysis Set ................................................................................................8 
4.3. Safety Analysis Set ..........................................................................................................8 
4.4. Other Analysis Sets .........................................................................................................8 
5. GENERAL METHODOLOGY AND CONVENTIONS ............................................................9 
5.1. Hypotheses and Decision Rules ......................................................................................9 
5.2. Sample Size Determination .............................................................................................9 
5.3. General Methods ...........................................................................................................10 
5.4. Methods to Manage Missing Data ................................................................................10 
 Efficacy Endpoints ............................................................................................10 
5.4.1.
 PK endpoints .....................................................................................................10 
5.4.2.
6. ANALYSES AND SUMMARIES ............................................................................................11 
6.1. Primary Endpoint(s) ......................................................................................................11 
 TEAEs, withdrawal due to AEs, and SAEs - Safety ........................................11 
6.1.1.
 Endoscopic improvement at Week 14 - Efficacy .............................................12 
6.1.2.
 Primary Efficacy Analysis ..............................................................12 
6.1.2.1.
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 Sensitivity Analysis 1 ......................................................................12 
6.1.2.2.
 Sensitivity Analysis 2 ......................................................................12 
6.1.2.3.
 Sensitivity Analysis 3 ......................................................................12 
6.1.2.4.
6.2. Secondary Endpoint(s) ..................................................................................................13 
 Remission and endoscopic remission ...............................................................13 
6.2.1.
 PF-06480605 serum concentrations .................................................................13 
6.2.2.
 ADAs and NAbs ...............................................................................................16 
6.2.3.
 Biomarkers (Fecal calprotectin, hsCRP) and serum total sTL1A ....................17 
6.2.4.
 
6.4. Subset Analyses .............................................................................................................18 
6.5. Baseline and Other Summaries and Analyses ...............................................................18 
 Demographic Data and Disease Characteristics ...............................................18 
6.5.1.
 Study Conduct and Subject Disposition ...........................................................18 
6.5.2.
6.6. Safety Summaries and Analyses ...................................................................................18 
7. INTERIM ANALYSES .............................................................................................................19 
7.1. Introduction ...................................................................................................................19 
7.2. Interim Analyses and Summaries ..................................................................................19 
8. REFERENCES ..........................................................................................................................19 
9. APPENDICES ...........................................................................................................................20 
 
LIST OF TABLES 
Table 1 Summary of Major Changes in SAP Amendments ............................................................4 
Table 2 PK Parameters to be Derived ............................................................................................15 
Table 3 PK Parameters to be Summarized Descriptively ..............................................................16 
 
APPENDICES 
Appendix 1. STATISTICAL METHODOLOGY DETAILS ........................................................20 
 
 
 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
1. VERSION HISTORY 
This Statistical Analysis Plan (SAP) for study B7541002 is based on the study protocol 
amendment 2 dated  12Jan2017.   
Table 1 Summary of Major Changes in SAP Amendments 
SAP Version Date 
Summary of Major Changes 
2 
30-Jan-2017 
x In Section 3.3, a revision is made to align with 
protocol amendment 2 on the endpoint of clinical 
response.  “Clinical response at Week 14 
(defined as a decrease from baseline in total 
Mayo score by at least 3 points and at least 30%, 
with a decrease in rectal bleeding subscore of at 
least 1 point or an absolute subscore of 0 or 1)”. 
x In Section 4.2, the definitiona of the Per Protocol 
population is revised per team agreement. “This 
set is defined as the Per Protocol Population 
which consists of subjects who are eligible for 
enrolment, not a major protocol violator, with at 
least 6 out of 7 planned doses received and a 
final colonscopy at Week 14.” 
 
1 
20-June-2016 Not applicable (original SAP) 
 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study B7541002.  This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment. 
 
2.1. Study Objectives 
 Primary Objectives 
2.1.1.
x To evaluate the safety and tolerability of PF-06480605 in subjects with moderate to 
severe Ulcerative Colitis (UC). 
x To evaluate the efficacy of PF-06480605 in induction of endoscopic 
improvement (as assessed by Mayo endoscopic subscore) at Week 14 in subjects 
with moderate to severe UC. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 Secondary Objectives 
2.1.2.
x To evaluate the efficacy of PF-06480605 in induction of remission at Week 14 
(defined as a total Mayo score d2 with no individual subscore >1) in subjects with 
moderate to severe UC. 
x To evaluate the efficacy of PF-06480605 in induction of endoscopic remission at 
Week 14 (defined as a Mayo endoscopic subscore of 0) in subjects with moderate to 
severe UC. 
x To describe the PK of PF-06480605 in subjects with moderate to severe UC. 
x To evaluate the immunogenicity of PF-06480605 in subjects with moderate to severe 
UC. 
x To evaluate disease and pathway related biomarkers (ie, high sensitivity C-reactive 
protein [hsCRP] and fecal calprotectin), and serum soluble TL1A (sTL1A). 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
2.2. Study Design 
This is a Phase 2a, single arm study in subjects with moderate to severe UC.  All subjects 
will receive 500 mg of PF-06480605 intravenously every 2 weeks (Q2W) for a total of 
7 doses.  The Simon’s two-stage design is adopted for the study. At the end of the first stage 
(12 evaluable subjects with a Week 14 colonoscopy), an interim analysis (IA) will be 
performed for an early efficacy assessment.  Enrollment in the second stage will be stopped if 
the futility criteria are met and any ongoing subjects in the second stage will be moved to the 
follow-up period.  Otherwise, recruitment will continue in the second stage until 
approximately 36 total evaluable subjects complete the study with a final colonoscopy at 
week 14 for final efficacy assessment. Details of the decision criteria are documented in 
Section 5.1.  
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint(s) 
x Safety and tolerability of PF-06480605: treatment emergent adverse events (TEAEs), 
withdrawal due to adverse events (AEs), and serious adverse events (SAEs) will be 
reported. 
x Endoscopic improvement at Week 14 (defined as a Mayo endoscopic subscore of 0 
or 1, and without friability). 
3.2. Secondary Endpoint(s) 
x Remission at Week 14 (defined as a total Mayo score d2 with no individual subscore 
>1). 
x Endoscopic remission at Week 14 (defined as a Mayo endoscopic subscore of 0). 
x PF-06480605 plasma concentrations. 
x Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies 
(NAbs).  
x Change from baseline in fecal calprotectin. 
x Change from baseline in hsCRP. 
x Change from baseline in serum total sTL1A. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 
3.4. Baseline Variables 
Demographics and medical history will be collected only at baseline. These baseline values 
will be summarized descriptively.  
  
4. ANALYSIS SETS 
4.1. Full Analysis Set 
The Full Analysis Set (FAS) is defined as the All Treatment Population which consists of 
subjects who have received at least one dose of PF-06480605.  This is the primary analysis 
population for the safety and treatment compliance. This population will also be used to 
analyze efficacy endpoints in sensitivity analyses.  
 
4.2. Per Protocol Analysis Set  
The Per Protocol Analysis Set (PPAS) will be a subset of the FAS dataset.  This set is 
defined as the Per Protocol Population which consists of subjects who are eligible for 
enrolment, not a major protocol violator, with at least 6 out of 7 planned doses received and a 
final colonscopy at Week 14. The Per Protocol Population is the primary analysis population 
for efficacy in this study.   
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in 
Per Protocol analysis population prior to receiving the Week 14 colonscopy results from 
Robarts and classifications will be documented per standard operating procedures. 
4.3. Safety Analysis Set 
The Safety analysis set is same as the FAS. This analysis set is the primary analysis 
population for treatment compliance and safety. Subjects who are not treated will be 
excluded from the safety analyses.   
4.4. Other Analysis Sets 
The PK concentration population is defined as all enrolled subjects who received at least one 
dose of PF-06480605 and in whom at least one concentration value is reported. 
The PK parameter population is defined as all enrolled subjects who received at least one 
dose of PF-06480605 and had at least one derived value of a specific PK parameter. 
The immunogenicity assessment population is defined as all enrolled subjects who received 
at least one dose of PF-06480605 with at least one post-treatment anti-drug (PF-06480605) 
antibody determination. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
The biomarker analysis population is defined as all enrolled subjects who received at least 
one dose of PF-06480605 with at least one biomarker assessment. 
5. GENERAL METHODOLOGY AND CONVENTIONS 
5.1. Hypotheses and Decision Rules 
This study employs Simon’s two-stage design.  Let p be the proportion of subjects achieving 
endoscopic improvement at Week 14 and the following hypotheses will be tested in this 
study: 
H0: p d 6% versus H1: p t 41%,  
where 6% was the observed placebo endoscopic improvement rate in anti-TNF experienced 
subjects from two tofacitinib Phase 3 induction studies (A3921094 and A3921095) in 
subjects with UC.  In the first stage, it is planned to have 12 evaluable subjects with 
colonoscopy at Week 14.  If no more than 2 subjects have achieved endoscopic improvement 
AND no subject has achieved endoscopic remission, then the study will be stopped for 
futility; otherwise, the study will continue to enroll until 36 evaluable subjects complete the 
study with colonoscopy at Week 14.    
The point estimate of endoscopic improvement rate, 2-sided 95% confidence interval and p-
value will be calculated using the method described in Koyama and Chen (2008) and Jung 
and Kim (2004) according to the actual sample size in the primary analysis population. 
Details of the methodology is documented in the Appendix 1.   
A p-value of less than 0.05 corresponds to a statistically significant result; however, to 
establish a clinically significant result, it is required to have at least 9 subjects achieve 
endoscopic improvement at Week 14 out of 36 evaluable subjects (i.e. at least 25% of 
evaluable subjects achieveing endoscopic improvement at Week 14) at the end of the second 
stage. If the actual number of evaluable subjects in the Per Protocol population is different 
from 36 at the end of the second stage, then it is required to have at least 25% subjects 
achieve endoscopic improvement at Week 14 for rejection of the null hypothesis H0 
clinically. 
5.2. Sample Size Determination 
The sample size was determined based on the primary endpoint of endoscopic improvement 
at Week 14 using Simon’s two-stage design.  The operating characteristics of the design 
described in Section 5.1 were assessed through Monte Carlo simulations.  With 12 evaluable 
subjects in the first stage and a maximum total of 36 evaluable subjects and the H0 rejection 
criterion described in Section 5.1, the Simon’s two-stage design has at least 90% power 
under the alternative hypothesis H1 while the type-I error is less than 0.001.  On the other 
hand, the probability of stopping early for futility in the first stage is at least 86% under the 
null hypothesis H0 and an endoscopic remission rate of 1%. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
5.3. General Methods  
This is a single-arm study without treatment comparisons. All the study endpoints will be 
summaried using descriptive statistics. For binary endpoints, summary statistics including the 
numbers, percentages and confidence intervals will be presented. For continuous endpoints, 
descriptive statistics (n, mean, median, standard deviation, minimum and maximum) will be 
presented, by each planned measurement time point if applicable. Inter-quartile ranges and 
95% confidence intervals may be provided where meaningful. Geometric mean and 
coefficient of variation (CV) may be provided as necessary for certain PK parameters.   
5.4. Methods to Manage Missing Data 
 Efficacy Endpoints 
5.4.1.
Subjects who don’t have a final colonscopy performed at Week 14 will be excluded from the 
primary efficacy analysis; the non-responder imputation method will be applied for these 
subjects in FAS population anlaysis.  
The Mayo scores will be calculated based on the subject’s diary data recorded over the 
3 prior consecutive days prior to the endoscopy bowel preparation procedure. For baseline 
endoscopy and post-baseline endoscopy, if there are missing diary data, the average will be 
taken from the 3 most recently available days reported within 5 days prior to the endoscopy 
preparation.  
If there are less than 3 available days reported within the 5 days prior to the study visit, the 
average will be taken from the limited available data unless there is no diary data reported 
within 5 days.  In this case, stool frequency and rectal bleeding subscores will be considered 
as missing. 
For Mayo score related endpoints (remission, endoscopic remission, symptomatic remission, 
deep remission, histologic remission, clinical response), the non-responder imputation 
method will be applied for FAS population anlaysis. 
 PK endpoints 
5.4.2.
 
In all data presentations (except listings), PF-06480605 concentrations below the limit of 
quantification (BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, 
where LLQ will be replaced with the value for the lower limit of quantification.) 
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if one of the following cases is true: 
1. A concentration has been collected as ND (ie not done) or NS (ie no sample), 
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
Note that PK summary statistics will not be presented at a particular time point if more than 
50% of the PK data are missing. 
If data permits, PK parameters may be derived from the PF-06480605 serum concentrations 
in which case the actual PK sampling times will be used in the derivation of these PK 
parameters. If a PK parameter cannot be derived from a particular subject’s concentration 
data, the parameter will be coded as NC (ie not calculated). (Note that NC values will not be 
generated beyond the day that a subject discontinues.) 
In PK summary tables, statistics will be calculated by setting NC values to missing; and 
VWDWLVWLFVZLOOEHSUHVHQWHGIRUDSDUWLFXODUGRVHZLWKHYDOXDEOHPHDVXUHPHQWV If an 
individual subject has a known biased estimate of a PK parameter (due for example to an 
unexpected event such as vomiting before all the compound is adequately absorbed in the 
body), this will be footnoted in summary tables and will not be included in the calculation of 
summary statistics or statistical analyses. 
Immunogenicity assay titers will be used to determine incidence for ADA and NAb. If a titer 
value is missing data imputation will not occur and missing values will be represented by 
NC. Data permitting, descriptive statistics will be provided. 
For other endpoints, statistical analyses will be based on available data. Missing data will not 
be imputed.  
6. ANALYSES AND SUMMARIES 
All analyses and summaries will be performed following Pfizer data standards.  
6.1. Primary Endpoint(s) 
 TEAEs, withdrawal due to AEs, and SAEs - Safety 
6.1.1.
o Definition: A treatment-emergent adverse event (TEAE) is defined as an event 
that emerges during treatment having been absent pre-treatment, or worsens 
relative to the pre-treatment state. 
o Analysis population:  FAS  
o Analysis methodology:  descriptive statistics    
o Supporting objective: Primary Objective 
o Reporting results: 
x The sample size, number of events, number of subjects with event and 
percentage of subjects with event  
 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 Endoscopic improvement at Week 14 - Efficacy 
6.1.2.
 Primary Efficacy Analysis 
6.1.2.1.
o Analysis population:  PPAS  
o Analysis time points: Week 14 
o Analysis methodology:  See Appendix 1  
o Supporting objective: Primary Objective 
o Decision rule: Simon’s design decision rule (Section 5.1) 
o Reporting results: 
x The sample size, number of subjects with endoscopic improvement,   
x Endoscopic improvement rate point estimate (UMVUE), p-value, 95% 
confidence interval – Appendix 1 
x Maximum likelihood estimate (MLE) of endoscopic improvement rate, 
95% Clopper-Pearson confidence interval 
 
To support the interpretation of the primary efficacy endpoint, the following sensitivity 
analyses will be performed if the study proceeds to the stage 2: 
 Sensitivity Analysis 1 
6.1.2.2.
o Analysis population:  FAS  
o Analysis time points: Week 14 
o Analysis methodology: Descriptive statistics 
o Method of imputation for missing data: non-responder imputation    
o Reporting results: 
x The sample size, number of subjects with endoscopic improvement, 
endoscopic improvement rate (MLE), 95% Clopper-Pearson confidence 
interval 
 
 Sensitivity Analysis 2 
6.1.2.3.
o Analysis population:  subjects in FAS with a final colonscopy at Week 14  
o Analysis time points: Week 14 
o Analysis methodology: Descriptive statistics 
o Reporting results: 
x The sample size, number of subjects with endoscopic improvement, 
endoscopic improvement rate (MLE), 95% Clopper-Pearson confidence 
interval 
 
 Sensitivity Analysis 3 
6.1.2.4.
o Analysis population:  subjects in FAS with all planned dose received and a final 
colonscopy at Week 14 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
o Analysis time points: Week 14 
o Analysis methodology: Descriptive statistics 
o Reporting results: 
x The sample size, number of subjects with endoscopic improvement, 
endoscopic improvement rate (MLE), 95% Clopper-Pearson confidence 
interval 
 
6.2. Secondary Endpoint(s) 
 Remission and endoscopic remission 
6.2.1.
o Analysis population:  PPAS and FAS  
o Analysis time points: Week 14 
o Analysis methodology:  descriptive statistics    
o Method of imputation for missing data: non-responder imputation    
o Supporting objective: Secondary Objective 
o Reporting results: 
x The sample size, number of subjects with remissions, remission rate 
estimates (MLE), 95% Clopper-Pearson confidence intervals  
 PF-06480605 serum concentrations 
6.2.2.
o Analysis populations:  PK concentration population.  
o Analysis time points:  all visits with PK samples taken 
o Analysis methodology:  summary statistics will be provided for plasma 
concentrations.  
o Supporting objective: Secondary Objective 
o Reporting results: 
x Presentations for PF-06480605 concentrations will include: 
o a listing of all concentrations sorted by subject ID, cohort, and 
nominal time post-dose.  The concentration listing will also include 
the actual times.  Deviations from the nominal time will be given 
in a separate listing. 
o a summary of concentrations by nominal time post-dose, where the 
set of statistics will include n, mean, median, standard deviation, 
coefficient of variation (CV), minimum, maximum, and the 
number (percentage) of concentrations above the lower limit of 
quantification (LLQ).  
o median concentrations time plots (on both linear and semi-log 
scales) against nominal time post-dose  
o mean concentrations time plots (on both linear and semi-log 
scales) against nominal time post-dose 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
o individual concentration time plots by subject (on both linear and 
semi-log scales) against actual time post-dose (there will be 
separate plots for each subject per scale). 
The length of time used for the x-axes of these plots will be decided on 
review of the data, and will depend on how long PF-06480605 
concentration is quantifiable in the matrix. For summary statistics, median 
and mean plots by sampling time, the nominal PK sampling time will be 
used, for individual subject plots by time, the actual PK sampling time will 
be used. 
o If data permits, non-compartmental PK parameters in Table 2 below may be 
derived from the PF-06480605 serum concentrations.  
x PK parameters will be summarized by visit or dosing day and will include 
the set of summary statistics as specified in the Table 3. 
x Analysis population: PK parameter population. 
 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
Table 2 PK Parameters to be Derived 
Parameter 
Definition 
Method of Determination 
$8&Ĳ 
Area under the concentration-time profile from 
WLPH]HURWRWLPHWDXĲWKHGRVLQJLQWHUYDO
where tau = 14 days  
Linear/Log trapezoidal method 
AUClast 
Area under the concentration-time profile from 
time zero to the time of the last quantifiable 
concentration (Clast). 
Linear/Log trapezoidal method 
Tlast 
Time of last quantifiable concentration (Clast) 
Observed directly from data  
AUCinf 
Area under the concentration-time profile from 
time zero extrapolated to infinite time. 
AUClast + (Clast*/kel), where Clast* is the 
predicted serum concentration at the last 
quantifiable time point estimated from the log-
linear regression analysis. 
Cmax 
Maximum serum concentration during the 
dosing interval 
Observed directly from data 
Tmax 
Time for Cmax 
Observed directly from data as time of first 
occurrence 
t½ 
Terminal half-life 
Loge(2)/kel, where kel was the terminal phase 
rate constant calculated by a linear regression 
of the log-linear concentration-time curve.   
CL 
Clearance 
'RVH$8&Ĳ 
MRT 
Mean residence time 
AUMCinf/AUCinf where AUMCinf is the area 
under the first moment curve derived using the 
linear/log trapezoidal method 
Cmin 
Lowest concentration observed during the 
dosing interval 
Observed directly from data 
Cav 
Average concentration 
$8&ĲĲ 
Rac 
Observed accumulation ratio 
Day 85 $8&Ĳ'D\$8&Ĳ 
Rac,Cmax 
Observed accumulation ratio for Cmax 
Day 85 Cmax / Day 1 Cmax 
PTR 
Peak-to-trough Ratio 
(Cmax/Cmin) 
Vss 
Volume of distribution at steady state (IV 
Dose) 
CLxMRT 
 
 
 
 
 
 
 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
Table 3 PK Parameters to be Summarized Descriptively 
Parameter 
Summary Statistics 
AUCĲ AUCinf*, AUClast, Cmax, 
Cmin, Cav, CL, Vss Rac, Raccmax, 
PTR, MRT 
N, arithmetic mean, median, cv%, standard deviation, minimum and 
maximum. Also geometric mean and cv(%) if no BLQ. 
Tmax, Tlast 
N, median, minimum, maximum 
t1/2 
N, arithmetic mean, median, cv%, standard deviation, minimum, maximum 
 
There will be one summary table presenting all PK parameters.  Supporting data from the 
estimation of t½ and AUCinf will be listed by visit or dosing day where applicable:  terminal 
phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2); the percent 
of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of time points 
used in the estimation of kel.  This data may be included in the clinical study report. 
 
 ADAs and NAbs 
6.2.3.
o Analysis population:  immunogenicity assessment population 
o Analysis time points:  all visits with samples taken 
o Analysis methodology:  summary statistics   
o Supporting objective: Secondary Objective 
o Reporting results: The incidence of development of ADA NAb against PF-
06480605 will be presented.  Presentations for immunogenicity will include:  
x Summary of ADA and Nab analysis by sample 
x Summary of ADA and Nab analysis by Subject 
x Summary of cumulative incidence of ADA and NAb over time 
x Summary of ADA and NAb incidence over time 
x Data permiting PK parameters by ADA and NAb status 
x Endoscopic improvement, remission and endoscopic remission endpoints 
by ADA and NAb status 
x Listing of individual level ADA and NAb response 
Additionally, data permitting the following figures may be provided: 
x Impact of ADA and NAb status of PF-06480605 concentrations  
x Impact of ADA and NAb status on biomarkers 
x Impact of ADA and NAb status on endoscopic improvement, remission 
and endoscopic remission endpoints 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
 Biomarkers (Fecal calprotectin, hsCRP) and serum total sTL1A 
6.2.4.
o Analysis population:  biomarker analysis population 
o Analysis time points:  all visits with samples taken  
o Analysis methodology:  summary statistics   
o Supporting objective: Secondary Objective 
o Reporting results: 
x Change from baseline: The sample size, mean, standard deviation, median, 
minimum and maximum by visit 
x Absolute values: The sample size, mean, standard deviation, median, 
minimum and maximum by visit 
o Presentations for biomarker concentrations will also include: 
x a listing of all concentrations sorted by subject ID, cohort, and nominal 
time post-dose.  The concentration listing will also include the actual 
times.  Deviations from the nominal time will be given in a separate 
listing. 
x a summary of concentrations by nominal time post-dose, where the set of 
statistics will include n, mean, median, standard deviation, CV, minimum, 
maximum and the number of concentrations above the lower limit of 
quantification. 
x median concentrations time plots (on both linear and semi-log scales) 
against nominal time post-dose  
x mean concentrations time plots (on both linear and semi-log scales) 
against nominal time post-dose 
x individual concentration time plots by subject (on both linear and semi-log 
scales) against actual time post-dose (there will be separate plots for each 
subject per scale). 
The length of time used for the x-axes of these plots will be decided on review of 
the data, and will depend on how long the respective biomarker concentration is 
quantifiable in the matrix. For summary statistics, median and mean plots by 
sampling time, the nominal biomarker sampling time will be used, for individual 
subject plots by time, the actual biomarker sampling time will be used. 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
6.4. Subset Analyses  
Subgroup analyses for subjects who had prior use of conventional UC therapy (steroids, TNF 
inhibitors, immunosuppresants, or integrin inhibitors) will be performed descriptively for 
primary and secondary efficacy endpoints specified in Section 3.1 and 3.2, respectively. 
 
6.5. Baseline and Other Summaries and Analyses 
The baseline value is defined as the last non-missing measurement collected prior to 
administration of the first dose of PF-06480605 on day 1. If there are multiple measurements 
at baseline, then the average of the multiple measurements will be used as baseline value. 
 Demographic Data and Disease Characteristics 
6.5.1.
A breakdown of all subjects will be provided by demographic characteristics (age, race, 
weight, body mass index, and height), extent of disease (proctitis, procto-sigmoiditis, left-
sided colitis, extensive colitis, pancolitis) and prior use of conventional therapy for UC 
(steroids, TNF inhibitors, immunosuppresants, integrin inhibitors) in accordance with Pfizer 
data standards. Baseline Mayo scores (total and partial) and each domain score will be 
summaried descriptively. 
 Study Conduct and Subject Disposition 
6.5.2.
Subject evaluation groups will show end of study subject disposition and will show which 
subjects were analyzed for PK, PD, as well as for safety (adverse events and laboratory data).  
Frequency counts will be supplied for subject discontinuation(s) by treatment.  
6.6. Safety Summaries and Analyses 
All safety endpoints will be summarized descriptively in tabular and/or graphical format and 
listed, where appropriate, in accordance with Pfizer data standards. 
The analysis population for safety is described in Section 4.3. Safety and tolerability will be 
assessed by clinical review of all relevant parameters including adverse events (AEs) and 
laboratory tests.  
 
In addition to the analyses described for the safety endpoints in Section 6.1.1 (TEAEs, 
withdrawl due to AEs and SAEs) and Section 6.2.3 (ADAs and NAbs), summary statistics 
will be provided for the laboratory parameters, vital sign and ECG data. Absolute values and 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
change from baseline in laboratory safety parameters, vital signs and ECG parameters will be 
summarized descriptively. The incidence of laboratory test abnormalities will also be 
summarized if applicable.  
7. INTERIM ANALYSES 
7.1. Introduction 
A formal interim analysis (IA) is planned at the end of the first stage for futility assessment 
when 12 evaluable subjects complete the study with the Week 14 colonoscopy. The IA will 
be performed by the study team. The results and decision of the IA will be reviewed and 
endorsed by sponsor senior management.  
An early PK readout of PF-06480605 serum concentrations will be conducted after at least 6 
subjects have completed the Week 4 visit. This analysis will be done by the team clinical 
pharmacologist to confirm that the observed median Cav of PF-06480605 in UC patients after 
two doses of PF-06480605 are within a 2-fold range of the  expected Cav value of 154.8 
ug/mL (Study B7541001 healthy volunteer data).  Following this early PK readout analysis, 
if a greater than 2-fold difference in Cav is observed, then dose may be modified to match the 
exposures observed in healthy volunteers receiving 500 mg/kg IV (Study B7541001).  The 
results of the analysis will be documented in a memo and archived.  
The sponsor may conduct ongoing reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating PK/PD modeling, and/or support clinical 
development. 
7.2. Interim Analyses and Summaries 
This SAP will also serve as the IA analysis plan.  The delivery for IA will consist of analyses 
and summaries specified in this SAP in Sections 5 and 6 for the first stage data. The analysis 
approach prespecified for the first stage data will be used for IA. Futility assessment at IA 
will be performed using futility criteria specified in the Section 5.1.  
8. REFERENCES  
Jung SH. and Kim KM. [2004]. On the estimation of the binomial probability in multistage 
clinical trials. Stat Med. 23(6): 881-96. 
Koyama T. and Chen H. [2008]. Proper inference from Simon’s two-stage designs. Stat Med. 
27(16):3145-54. 
 
 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
9. APPENDICES  
Appendix 1. STATISTICAL METHODOLOGY DETAILS  
This appendix is based on the methodology in Jung and Kim (2004) for point estimation and 
Koyama and Chen (2008) for p-value and confidence interval.  
Let the null hypothesis be H0ʌ  ʌ0. A Simon’s two-stage design is usually indexed by four 
numbers that represent the stage 1 sample size  (n1), stage 1 criterial value (r1), final sample 
size (nt) and final critical value (rt). In stage 1, a sample size n1 is taken. If the number of 
successes X1 in stage 1 satifies X1U1, the trial is stopped for futility; otherwise, an additional 
sample of size n2 = nt – n1 is taken. Let X2 be the number of successes in stage 2 and let 
Xt=X1+X2. If Xtrt, futility is concluded; otherwise efficacy is concluded by rejecting H0.  
Let m be the stopping stage and S be the total number of successes accumulated up to 
stopping stage. That is, S=X1 when m=1 and S=Xt when m=2. If m=2 then let ݊ଶ
כ be the 
actual stage 2 sample size. Let x1 and x2 be the actual observed numbers of successes at stage 
1 and stage 2 (if m=2), respectively. Let s be the total number of successes observed at the 
end of the trial. 
Point Estimate: 
The maximum likelihood estimator (MLE) – ߨො௠௟௘  
ߨො௠௟௘= ൞
ݔଵ
݊ଵ
                            ݉= 1
ݔଵ+ ݔଶ
݊ଵ+ ݊ଶ
כ                   ݉= 2
 
The MLE estimator is unbiased when m=1. However, it is biased when m=2 and the 
following UMVUE estimator is unbiased and preferred (Jung and Kim, 2004). 
The uniformly minimum variance unbiased estimator (UMVUE) –  ߨො௨௠௩௨௘  
ߨො௨௠௩௨௘=
ە
ۖ
۔
ۖ
ۓ
ݔଵ
݊ଵ
                                                                     ݉= 1
σ
ቀ௡భିଵ
௫భିଵቁቀ௡మכ
௦ି௫భቁ
௦ٿ௡భ
௫భୀ(௥భାଵ)ڀ(௦ି௡మכ)
σ
ቀ௡భ
௫భቁቀ௡మכ
௦ି௫భቁ
௦ٿ௡భ
௫భୀ(௥భାଵ)ڀ(௦ି௡మכ)
           ݉= 2
 
where ܽٿܾ= min (ܽ, ܾ) and ܽڀܾ= max (ܽ, ܾ).  
P-value: 
If m=1 then the p-value is ݌= ܲగబ(ܺଵ൒ݔଵ). 
 
 
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Protocol B7541002 (PF-06480605)                                                                                    Statistical Analysis Plan 
 
If m=2 and the actual sample size in stage 2 is the same as the planned (i.e. ݊ଶ
כ = ݊ଶ), then 
the p-value is computed as 
݌=
෍
ܲగబ[ܺଵ= ݔଵ]ܲగబ[ܺଶ൒ݔଶ|ܺଵ= ݔଵ]
௡భ
௫భୀ௥భାଵ
 
Where ܺଶ~ܤ݅݊݋݈݉݅ܽ(݊ଶ, ߨ଴).  
If m=2 and the actual sample size in stage 2 is different from the planned (i.e. ݊ଶ
כ ്݊ଶ), then 
the p-value is computed as  
݌=
෍
ܲగబ[ܺଵ= ݔଵ]ܣ(ݔଵ, ݊ଶ, ߨכ),
௡భ
௫భୀ௥భାଵ
 
where ܣ(ݔଵ, ݊ଶ, ߨ) = ܲగ[ܺଶ൒ݎ௧െݔଵ|݊ଶ] = σ
ቀ௡మ
௫మቁ
௡మ
௫మୀ௥೟ି௫భାଵ
ߨ௫మ(1 െߨ)(௡మି௫మ) is the 
conditional power function at the second stage and ߨכ is the solution of  
ܣ(ݔଵ, ݊ଶ, ߨכ) = ܲగబ[ܺଶ
כ ൒ݔଶ|݊ଶ
כ], 
where ܺଶ
כ~ܤ݅݊݋݈݉݅ܽ(݊ଶ
כ, ߨ଴). 
 
Confidence interval 
If m=1, the exact 95% confidence interval will be computed using Clopper-Pearson method.  
If m=2, we can compute a p-value using the approach described above for testing H0ʌ  ʌ0 
IRUDQ\ʌ0.  A 2-sided 95% FRQILGHQFHLQWHUYDOLVDFROOHFWLRQRIʌ0 such that the 
corresponding p-value is within [0.025, 0.975]  
 
 
 
 
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