Conditions: Ulcerative Colitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 20
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine if PF-06687234 is effective and safe as add-on therapy to infliximab in subjects with active ulcerative colitis who are not in remission.

Detailed description:
This is a Phase 2a, double-blind, placebo-controlled, parallel group study in subjects with active ulcerative colitis and a non-remission (partial) response to infliximab. All enrolled subjects must have been on infliximab for a minimum of 14 weeks with last dose 8 weeks prior to the date of randomization. Subjects will be randomly assigned to 1 of 2 treatment arms (PF-06687234 or placebo) administered subcutaneously every week for a total of 12 doses. Blood, stool and tissue samples will be collected at various time points throughout the study to evaluate efficacy, safety, tolerability, pharmacokinetics and immunogenicity. Duration of participation for subjects will be approximately 6 months.

Arms:
arm 1: PF-06687234 subcutaneous (SC) weekly (QW) x 12 doses arm 2: PF-06687234 matched Placebo SC QW x 12 doses

Interventions: intervention 1: PF-06687234 intervention 2: Placebo
Intervention descriptions: intervention 1: SC QW intervention 2: SC QW

Protocol document:
Prot_000.pdf: 
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A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND 
PHARMACOKINETICS OF PF-06687234 AS ADD-ON THERAPY TO INFLIXIMAB 
IN ACTIVE ULCERATIVE COLITIS SUBJECTS WHO ARE NOT IN REMISSION
(BUILD UC)
Investigational Product Number:
PF-06687234
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug Application (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2017-002108-28
Protocol Number:
B7581002
Phase:
2A
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
CCI


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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 4
(US only)
10 April 2020

Section 9.1 and 9.5: Modified the interim 
analysis for futility to be performed with
approximately 20% and 40% randomized 
subjects for 12-week treatment.
Rationale: The early interim analysis for futility
with approximately 20% randomized subjects
was added to enable early internal decision 
making.
Amendment 3
30 August 2018

Schedule of Activities, Section 2, 7.5.1, 7.5.2
and 7.5.3: Changed to reflect serum PK
sampling for PF-06687234.
Rationale: Serum sample rather than plasma will 
be used for PF-06687234 PK assay.

Schedule of Activities footnote v, Section 3.2, 
and 6.4: Added text for subject discontinuation
in the presence of detectable NAb against IL-10 
portion of PF-06687432.
Rationale: Clarified immunogenicity monitoring 
process for early withdrawal of subjects due to 
detectable NAb against IL-10 portion of 
PF-06687432.

Section 4.3: Changed to state “Subjects will have 
up to 4 weeks after the first screening visit to 
complete all screening procedures prior to 
randomization.”
Rationale: Clarified randomization criteria to be 
consistent with Section 6.1.

Section 6.2.1: Widened the interval from 
approximately 1 hour to ‘approximately 1 hour 
but not exceed 3 hours’ between infliximab 
infusion completion and IP dosing.
Rationale: Allowing more time for a subject to 
travel from an infusion center (if applicable) to a 


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study site.

Section 7.6.1: Clarified to state “The positive 
samples will be further characterized in the NAb 
assays, if bioanalytically feasible”.
Rationale: To clarify that positive ADA samples 
will be further tested for NAb.

Schedule of Activities footnote h: Added text 
“The total Mayo score at Week 0 will be 
calculated based stool frequency, rectal bleeding 
and endoscopy performed during screening 
period and PGA obtained at baseline.”
Rationale: To clarify the procedure for 
calculation of total Mayo score.

Section 1.3.1 Study Rationale: Inserted a 
paragraph to recognize the changes to standard 
of care that use alternative dosing intervals of 
infliximab to manage UC subjects in clinical 
practice.  
Rationale: To provide rationale, references, and 
practice guidance to allow infliximab dosing 
every 6 weeks in the protocol.

Schedule of Activities, footnote y, Section 4, 
inclusion criterion 7, and exclusion criterion 6, 
Section 6.2.8, 6.2.15, and 6.2.17: Changed to 
allow subjects on infliximab dosing interval of 
every 6 weeks into the study and clarified the 
time requirement for study eligibility after
change of infliximab regimen (dosage and 
dosing interval).
Rationale: Optimizing infliximab dosing 
(adjusting either dosage or dosing intervals other 
than every 8 weeks in maintenance) is an 
evidence-based recommendation for managing
patients to achieve treatment target.  Clinical 
data support dose escalation and adjusting 
administration intervals to improve treatment 
efficacy. Based on new UC treatment 
guidelines, infliximab maintenance dosing 


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intervals more frequent than every 8 weeks are 
commonly prescribed in clinical practice as part 
of standard of care.  As infliximab is a 
background treatment in this study, allowing 
subjects on an infliximab dosing interval of 
every 6 weeks (in addition to subjects on an 
infliximab dosing interval of every 8 weeks) into 
the study will better align subject eligibility to 
current standard of care.  

Section 4.1, inclusion criterion 7: deleted “a 
maximum two years” limitation for background 
infliximab therapy for an eligible subject.
Rationale: There is no evidence to support the 
exclusion of subjects on background infliximab 
therapy for more than 2 years if they meet other 
eligibility criteria for study entry.

Section 3.1, and 9.1: Changed estimated sample 
size from 98 to 76 with estimated evaluable size 
of 32 in each group (64 in total) with 
15% dropout rate.
Rationale: The sample size has been revised 
based on likely dropout rate of 15% and 
one-sided alpha=0.05 type 1 error rate using 
organizational experience from recent clinical 
trials in ulcerative colitis (UC).

Schedule of Activities, Section 6.2.1: Added 
collection of infliximab ADA samples at 
baseline visit and at other study visits when 
administration of infliximab occurs. Added 
collection of infliximab trough samples at study 
visits when administration of infliximab occurs. 
Rationale: To establish baseline infliximab ADA
status and infliximab trough level for potential
inclusion in efficacy analyses.

Section 4.1, inclusion criterion 5: Modified the 
criterion to state “Subjects who have partial 
response to anti-TNF (infliximab) and active UC 
as defined by (via screening endoscopy) a total 
Mayo Score 4 but 9 and an endoscopic 


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subscore 2.
Rational: To widen the entry total Mayo score 
inclusion criterion allowing the inclusion of a 
wider, more representative sample of subjects 
with active UC. 

Section 4.1, inclusion criterion 6: Changed to 
state: “UC extending at least 15 cm proximal to 
the anal verge at the time of the screening 
endoscopy.”
Rationale: Modification will allow the inclusion 
of subjects with disease severity consistent with 
other inclusion criteria whilst still excluding 
subjects with isolated proctitis.

Section 4.2, exclusion criterion 4: Clarified the 
exclusion criterion to state: “Subjects with 
extensive colitis for at least 8 years who have not 
had a colonoscopy with surveillance biopsies 
within 2 years of the baseline visit.”
Rationale: To clarify that a colonoscopy is 
required for subjects with extensive colitis and 
without surveillance colonoscopy within 2 years
and that this surveillance can be performed 
during the screening colonoscopy if necessary.

Section 4.2, exclusion criterion 5: Clarified the 
exclusion criterion that subjects with prior 
history of adenomatous polyps will be eligible if 
the polyps have been completely removed and 
pathology is negative. 
Rationale: To clarify subject eligibility.

Section 4.2, exclusion criterion 24: Changed the
exclusion criterion eGFR to
<60 mL/min/1.73 mm2 based on age appropriate
calculation.
Rationale: No renal risk has been identified for 
PF-06687234 (or for rhIL-10 from the literature). 
Significant numbers of subjects with UC could 
have renal function that would place them in 


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Chronic Kidney Disease (CKD) stage II. The 
amended eGFR exclusion criterion will 
potentially allow the inclusion of a more 
representative population of UC without 
introducing a safety risk.

Section 4.2 exclusion criterion 13: Changed 
exclusion criterion to state: “Current evidence of 
active TB or latent TB infection or inadequately 
treated TB infection demonstrated by chest 
x-ray, a positive Mantoux (purified protein
derivative [PPD]) tuberculin skin test or a 
positive Interferon Gamma Release Assay 
(IGRA to be tested at the site’s local lab) during 
screening or within 12 weeks prior to
randomization. “ 
Rationale: As a standard of care, all UC patients 
need to receive a TB test for latent TB infection
and have adequate antimycobacterial treatment 
prior to initiation of infliximab therapy.  The 
revised exclusion criterion is to exclude subjects 
with evidence of active TB or latent TB patients 
without adequate treatment into the study. 

Section 1.2.1.1 Non-Clinical Safety and 
Section 1.3.2 Dosing Rationale: Updated the 
section with study results from 6-month toxicity 
study in mice and revised the safety margin to 
3.2x compared with a clinical dose of 
0.5 mg/kg/week on a body surface area basis in 
mice and 5.8x compared with a clinical dose of 
0.5 mg/kg/week on a body surface area basis in 
cynomolgus monkeys. 
Rationale: Updated with newly available 
6 months toxicity data in mice and revised the 
safety margin based on clinical dose of 
0.5 mg/kg/week.

Several additional minor changes and sentence 
revisions were made throughout the document.
Rationale: Revisions were made for the purpose 
of clarification and to correct any minor


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grammatical or spelling errors.
Amendment 2
06 March 2018

Section 1.2.2.1 Subject Disposition: Updated 
ongoing Philogen Dekavil study in RA subjects. 
Rationale: Updated enrollment and safety 
information in Philogen Dekavil RA study.

Section 4.1 Inclusion Criteria: Deleted “or 
legally acceptable representative” in Criterion #1
and in Sections 8.1.2 and 12.3.
Rationale: Global change to comply with 
regulatory feedback received not allowing 
inclusion of subjects who are unable to give the 
consent.

Section 4.1 Inclusion Criteria:  Modified the 
inclusion criterion #3 to add “weight >40 kg” as 
part of inclusion criterion.
Rationale: To exclude subjects with weight 
40 kg to avoid IP exposure >600 g/kg/week.

Section 4.2 Exclusion Criteria: Added exclusion 
criterion #30: “Known history of 
hypersensitivity, intolerance, or allergic reaction 
to PF-06687234 or any constituent of the IP”.
Rationale: To exclude subjects who had known 
history of hypersensitivity, intolerance or allergic 
reaction to PF-6687234 or any constituent of the 
IP.

Section 4.2 Exclusion Criteria: Updated the 
exclusion criterion #18 to “Exposure to a live 
(attenuated) vaccine within 30 days prior to 
screening or anticipated need for any live 
(attenuated) vaccine during the study.”
Rationale: To protect safety of the study 
participants and comply with regulatory request.

Section 4.4.1 Contraception: Removed ‘using 
male or female condom plus spermicide as a 
highly effective method of contraception’ and 
modified the contraception requirement to ‘2 


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methods of contraception (at least one of which 
is considered to be highly effective)’. 
Rationale: To comply with Clinical Trial 
Facilitation Group (CTFG) guidance of the 
Heads of Medicines Agency (HMA) which does 
not allow condom plus spermicide as a highly 
effective method.

Section 4.4.1 Contraception: Added “Male 
subjects must refrain from sperm donation for 
the duration of the active treatment period and 
until Week 16 or 28 days after the last dose of 
the investigational product.”
Rationale: For safety reasons and to comply with 
regulatory request. 

Added a new subsection 5.11 Rescue Medication 
with the following text: “Rescue therapy should 
be provided by the investigator as deemed 
clinically appropriate.  Subjects requiring rescue 
medication prior to the end of the study will be 
discontinued from IP (PF-06687234 or placebo) 
and will enter the follow-up period.  Subjects 
requiring rescue medication after Week 11 (after 
last IP administration) should also complete the 
follow-up period.” 
Rationale: To provide clarification that rescue 
therapy should be provided by investigators as 
deemed clinically appropriate and that subjects 
requiring rescue medication will be discontinued 
from the study. 

Section 5.2 Breaking the Blind: To clarify that if 
the immediate unblinding is necessary, the 
discussion between investigator and the member 
of study team member is not required in advance 
of unblinding.
Rationale: To protect the subject’s safety.

Section 5.4.3 Preparing and Dispensing, Section 
5.5 Administration: To clarify that IP and 
placebo are prepared by qualified unblinded site 


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staff and administration of prepared IP or 
placebo to subjects is performed by qualified 
blinded site staff.
Rationale: To clarify the process that preparation 
of IP and placebo are performed by unblinded 
site staff and administration of IP or placebo is
performed by blinded site staff. 

Section 6.4 Guidance for Monitoring and 
Discontinuation: Added a discontinuation 
criterion that a subject with detected neutralizing
antibody against IL-10 domain will be 
discontinued from the treatment and the study.
Rationale: To protect the safety of the study 
participants. 

References: Replace the reference #22 with 
“Chan ISF., Zhang Z. Test-based exact 
confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999; 55: 
1201–1209.”
Rationale: To provide the correct reference as the 
reference noted in earlier versions of the protocol 
was incorrect.

Several additional minor changes were made in 
the document.
Rationale: Revisions were made for the purpose 
of correcting any minor errors. 
Amendment 1
06 September
2017

Throughout the protocol modified language to 
allow the use of specific infliximab biosimilars. 
Rationale: To allow more flexibility for subjects 
who are currently treated with an infliximab 
biosimilar and minimize need to switch off of 
pre-study biosimilar to Remicadeduring the 
study.

Added Appendix 5 Protocol Specific Infliximab 
Biosimilars.
Rationale: To clarify in the protocol the 


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infliximab biosimilars that subjects will be 
allowed to be treated with during the study. Only 
listed biosimilars (in addition to Remicade) will 
be used, in order to allow for validated 
infliximab trough levels and anti-drug antibodies 
to be completed in timely fashion during the 
study.

Schedule of Activities and Sections 6.2.9 and 
6.2.10: Changed the collection of the serum 
infliximab concentration and ADA against 
infliximab from Visit 8 Week 7 to Visit 9 
Week 8.
Rationale: To more accurately capture the trough 
levels of infliximab and concurrent ADA 
immediately before dosing.

Section 4.1 Inclusion criteria:  Modified 
inclusion criterion #7 “Must be on a stable dose 
5-10 mg/kg of Remicade, Inflectraor 
Remsimafor a minimum of 14 weeks (4 doses) 
and a maximum of two years prior to study entry 
with no anticipation of need for change in 
infliximab treatment regimen throughout the 
study (no switches from pre-study infliximab 
version to a different infliximab version will be 
permitted).”
Rationale: To provide further clarification 
regarding the infliximab treatment regimen that 
is required at study entry and throughout the 
study.

Section 4.2 Exclusion criteria:  Exclusion criteria 
#24 modified hemoglobin level from 95 g/L 
(9.5 g/dL) to 100 g/L (10.0 g/dL).
Rationale: The minimum hemoglobin exclusion 
criterion was raised so as to not conflict with 
inclusion criteria #11.

Section 5.10.3 Prohibited Medications: Modified
from stating “Any iTNF treatment or biologic 
therapy other than Remicade12 weeks prior to 
screening and through Week 16” to stating “Any 


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non-infliximab iTNF treatment or biologic 
therapy within 24 weeks of screening visit.”
Rationale: To further clarify and cover the 
timeframe that iTNF treatment or biologic 
therapy other than infliximab iTNF treatment 
that would be prohibited during the study.

Section 5.10.3 Prohibited Medications: Modified 
from stating “Any investigational procedures(s) 
or product(s), such as immunomodulators used 
in transplantation (eg, mycophenolate mofetil, 
cyclosporine, rapamycin, or tacrolimus) or live 
(attenuated) vaccine within 30 days prior to 
baseline and through Week 16” to stating “Any 
investigational procedures(s) or product(s), such 
as immunomodulators used in transplantation 
(eg, mycophenolate mofetil, cyclosporine,
rapamycin, or tacrolimus)”.
Rationale: This is to correct a typographical 
error and duplicative language since live 
(attenuated) vaccine within 30 days prior to 
baseline and through Week 16 is already listed 
as a prohibited medication.

Section 6.2.15 Week 12/Early Withdrawal Visit: 
Modified from stating “PK: Plasma 
PF-06687234 concentration sample should be
collected approximately 30 minutes prior to 
dosing” to stating “PK: Plasma PF-06687234 
concentration sample should be collected”.  
Rationale: This is to correct a typographical 
error and to be consistent with the Schedule of 
Activities for the Week 12/Early Withdrawal 
visit during which there is no dosing of 
PF-06687234.

Section 6.4 Guidelines for Monitoring and 
Discontinuations: Removed the mandatory 
retesting of hemoglobin.
Rationale: Removed automatic hemoglobin
retesting criteria to limit the number of blood 
draws and leave it up to discretion of 


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investigator regarding retesting necessity and 
timing.

Section 6.4 Guidelines for Monitoring and 
Discontinuations: Added individual subject 
discontinuation criteria for specific AST or ALT 
result when co-occurring with specific 
symptoms.
Rationale: To provide additional guidance to 
regulators and investigators on individual subject 
discontinuation criteria for specific AST or ALT 
results when co-occurring with specific 
symptoms.

Section 6.4 Guideline for Monitoring and 
Discontinuations: Added the following specific 
language: In the event that 2 subjects on IP
develop the same AE MEDRA Preferred Term 
graded as severe intensity as defined in 
Section 8.3 or if 1 patient develops an SAE as 
defined in Section 8.2.3, and the event(s) are 
assessed as potentially causally related to the IP 
and not clearly related to the underlying disease 
process or other causes, an ad-hoc IRC meeting 
will be convened. At this time the IRC will 
make recommendations to the study team.  
These recommendations will be to stop the 
study, continue with modifications or continue 
with the study unchanged.
In addition, the sponsor will notify relevant 
regulatory authorities that such an ad-hoc IRC
meeting has been convened and will provide 
case details to relevant regulatory authorities 
within 15 days of making the determination to 
convene the IRC meeting.
Rationale: To further protect patient safety and 
to establish requirement for prompt ad-hoc IRC 
review meetings in setting where a severe AE or 
an SAE is assessed as potentially causally
related to the investigational product have been 
met and the required notification to relevant 
regulatory authorities regarding the ad-hoc IRC 


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meeting and relevant case details.

Appendix 2: Added Reference: Schroeder KW, 
Tremaine WJ and Listrup DM. NEJM 
1987;24;317(26) 1625-1629.
Rationale: To correct administrative error from 
original protocol.
Original 
protocol
22 May 2017
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................19
LIST OF FIGURES .................................................................................................................19
APPENDICES .........................................................................................................................19
PROTOCOL SUMMARY.......................................................................................................20
SCHEDULE OF ACTIVITIES................................................................................................24
1. INTRODUCTION ...............................................................................................................33
1.1. Mechanism of Action/Indication.............................................................................33
1.2. Background and Rationale ......................................................................................35
1.2.1. Drug Development Rationale .....................................................................35
1.2.1.1. Non-Clinical Safety...................................................................36
1.2.2. Previous Human Experience.......................................................................38
1.2.2.1. Subject Disposition ...................................................................38
1.2.2.2. Pharmacokinetic Results ...........................................................39
1.2.2.3. Immunogenicity Results............................................................40
1.2.2.4. Safety Results in Clinical Trials................................................40
1.3. Rationale..................................................................................................................42
1.3.1. Study Rationale...........................................................................................42
1.3.2. Dose Rationale............................................................................................43
1.3.3. Summary of Benefit and Risks...................................................................44
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................47
3. STUDY DESIGN.................................................................................................................48
3.1. Study Overview.......................................................................................................48
3.1.1. Additional Pharmacokinetic Sampling.......................................................49
3.2. Duration of Subject Participation............................................................................49
3.3. Approximate Duration of Study..............................................................................50
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................50
4.1. Inclusion Criteria.....................................................................................................50
4.2. Exclusion Criteria....................................................................................................52
4.3. Randomization Criteria ...........................................................................................57
4.4. Lifestyle Requirements ...........................................................................................57
4.4.1. Contraception..............................................................................................57


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4.5. Sponsor’s Qualified Medical Personnel..................................................................58
5. STUDY TREATMENTS.....................................................................................................59
5.1. Allocation to Treatment ..........................................................................................59
5.2. Subject Compliance.................................................................................................59
5.3. Breaking the Blind ..................................................................................................59
5.4. Investigational Product Supplies.............................................................................60
5.4.1. Dosage Form(s) and Packaging..................................................................60
5.4.2. Remicadeor Protocol Specific Infliximab Biosimilar Label 
Instructions.......................................................................................................60
5.4.3. Preparation and Dispensing........................................................................60
5.5. Administration.........................................................................................................61
5.6. Injection/Infusion Discontinuation..........................................................................61
5.7. Investigational Product Storage ..............................................................................63
5.8. Investigational Product Accountability...................................................................64
5.8.1. Destruction of Investigational Product Supplies ........................................64
5.9. Prior Medication(s) .................................................................................................64
5.10. Concomitant Medication(s) and Treatment(s) ......................................................64
5.10.1. Oral Corticosteroids Taken During the Study ..........................................64
5.10.2. Permitted Medications..............................................................................64
5.10.3. Prohibited Medications.............................................................................65
5.11. Rescue Medication ................................................................................................66
6. STUDY PROCEDURES .....................................................................................................66
6.1. Screening.................................................................................................................66
6.2. Study Period ............................................................................................................68
6.2.1. Baseline – Day 1.........................................................................................69
6.2.2. Additional PK Sampling Day 1, Day 2 and Day 4.....................................71
6.2.3. Week 1 (2 days)........................................................................................71
6.2.4. Week 2 (2 days)........................................................................................72
6.2.5. Week 3 (2 days)........................................................................................73
6.2.6. Week 4 (2 days)........................................................................................74
6.2.7. Week 5 (2 days)........................................................................................75
6.2.8. Week 6 (2 days)........................................................................................76


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6.2.9. Week 7 (2 days)........................................................................................77
6.2.10. Week 8 (2 days)......................................................................................78
6.2.11. Week 9 (2 days)......................................................................................80
6.2.12. Week 10 (2 days)....................................................................................81
6.2.13. Week 11 (2 days)....................................................................................82
6.2.14. Additional PK Sampling Week 11 (Day 78), Day 79 and Day 81...........83
6.2.15. Week 12 (2 days)/Early Withdrawal Visit .............................................83
6.2.16. Week 16 Onsite Follow-up (+2 days).......................................................85
6.2.17. If applicable, Week 18 (2 day) for Subjects on Infliximab Dosing 
Every 6 Weeks .................................................................................................86
6.2.18. Week 22 Telephone Contact (+2 days) ....................................................86
6.3. Subject Withdrawal.................................................................................................87
6.3.1. Withdrawal of Consent...............................................................................87
6.3.2. Lost to Follow-up .......................................................................................87
6.4. Guidelines for Monitoring and Discontinuations....................................................88
7. ASSESSMENTS..................................................................................................................90
7.1. Blood Volume .........................................................................................................90
7.2. Safety.......................................................................................................................90
7.2.1. Infections ....................................................................................................90
7.2.2. Laboratory...................................................................................................90
7.2.3. Pregnancy Testing ......................................................................................91
7.2.4. Purified Protein Derivative (PPD) Tuberculin Test....................................92
7.2.5. Interferon Gamma Release Assay Tuberculin Test....................................92
7.2.6. Screening for Clostridium Difficile............................................................93
7.2.7. Vital Signs (Blood Pressure, Pulse Rate, and Temperature) ......................93
7.2.8. Medical History, Physical Examination, Height and Weight.....................93
7.2.9. Electrocardiogram (ECG)...........................................................................94
7.2.10. Chest Radiograph......................................................................................94
7.3. Diagnostic and Efficacy Assessments.....................................................................95
7.3.1. Endoscopy...................................................................................................95
7.3.2. Biopsy Collection from Colonic Mucosa for Histology, RNA, 
Epigenetic, Tissue Concentration PF-06687234 and Tissue Protein...............95


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7.3.3. Mayo Score.................................................................................................96
7.3.4. Subject Bowel Movement Diary ................................................................97
7.3.5. Partial Mayo Score .....................................................................................98
7.3.6. Geboes Score ..............................................................................................98
7.3.7. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ........................98
7.4. Pharmacodynamics..................................................................................................98
7.4.1. Exploratory Serum Protein Biomarkers......................................................99
7.4.2. Exploratory Biomeasurement Immune Cells..............................................99
7.4.3. High-Sensitivity C-Reactive Protein (hsCRP)............................................99
7.4.4. Fecal Calprotectin.......................................................................................99
7.4.5. Stool Samples for Exploratory Biomarkers (Microbiome) ........................99
7.5. Pharmacokinetics ..................................................................................................100
7.5.1. Serum for Analysis of PF-06687234 and Serum for Analysis of 
Infliximab.......................................................................................................100
7.5.2. Additional PK Sampling...........................................................................101
7.5.3. Shipment of Serum Samples for Analysis of PF-06687234 and 
Serum for Analysis of Infliximab ..................................................................101
7.6. Immunogenicity ....................................................................................................101
7.6.1. Plasma for Analysis of Human Anti-Fusion Antibodies (HAFA), 
Neutralizing Antibodies (NAb) Against PF-06687234 and Anti-Drug 
Antibodies Against Infliximab.......................................................................101
7.7. Pharmacogenomics................................................................................................102
7.7.1. Gene Expression Analysis ........................................................................102
7.8. Banked Biospecimens ...........................................................................................103
7.8.1. Additional Research..................................................................................104
8. ADVERSE EVENT REPORTING....................................................................................104
8.1. Requirements.........................................................................................................104
8.1.1. Additional Details on Recording Adverse Events on the CRF.................105
8.1.2. Eliciting Adverse Event Information........................................................105
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)..........................................................................106
8.1.4. Time Period for Collecting AE/SAE Information....................................106
8.1.4.1. Reporting SAEs to Pfizer Safety.............................................106


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8.1.4.2. Recording Non-serious AEs and SAEs on the CRF ...............106
8.1.5. Causality Assessment ...............................................................................106
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................107
8.2. Definitions.............................................................................................................107
8.2.1. Adverse Events.........................................................................................107
8.2.2. Abnormal Test Findings ...........................................................................108
8.2.3. Serious Adverse Events ............................................................................108
8.2.4. Hospitalization..........................................................................................109
8.3. Severity Assessment..............................................................................................110
8.4. Special Situations ..................................................................................................110
8.4.1. Protocol-Specified Serious Adverse Events.............................................110
8.4.2. Potential Cases of Drug-Induced Liver Injury..........................................110
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................112
8.4.3.1. Exposure During Pregnancy....................................................112
8.4.3.2. Exposure During Breastfeeding ..............................................113
8.4.3.3. Occupational Exposure ...........................................................114
8.4.4. Medication Errors .....................................................................................114
8.4.4.1. Medication Errors....................................................................114
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................115
9.1. Sample Size Determination...................................................................................115
9.2. Efficacy Analysis ..................................................................................................115
9.2.1. Analysis of the Primary Endpoint.............................................................115
9.2.2. Analysis of Secondary Endpoints.............................................................116
9.3. Analysis of Other Endpoints .................................................................................116
9.3.1. Pharmacokinetic Analysis ........................................................................116
9.3.2. Immunogenicity Analysis.........................................................................117
9.4. Safety Analysis......................................................................................................117
9.5. Interim Analysis ....................................................................................................117
9.6. Data Monitoring Committee (Internal Review Committee) .................................118
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................118
11. DATA HANDLING AND RECORD KEEPING ...........................................................119


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11.1. Case Report Forms/Electronic Data Record .......................................................119
11.2. Record Retention.................................................................................................119
12. ETHICS............................................................................................................................120
12.1. Institutional Review Board/Ethics Committee....................................................120
12.2. Ethical Conduct of the Study ..............................................................................120
12.3. Subject Information and Consent........................................................................120
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................121
13. DEFINITION OF END OF TRIAL.................................................................................121
13.1. End of Trial in a Member State...........................................................................121
13.2. End of Trial in All Other Participating Countries...............................................121
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................121
15. PUBLICATION OF STUDY RESULTS........................................................................122
15.1. Communication of Results by Pfizer ..................................................................122
15.2. Publications by Investigators ..............................................................................122
16. REFERENCES ................................................................................................................124
LIST OF TABLES
Table 1.
Overview of F8IL10 and PF-06687234 Clinical Program (June 2018) ...............38
Table 2.
Laboratory Tests ...................................................................................................91
LIST OF FIGURES
Figure 1.
Structural Diagram of PF-06687234 ....................................................................20
Figure 2.
Structural Diagram of PF-06687234 ....................................................................34
Figure 3.
Study Design Schematic.......................................................................................49
APPENDICES
Appendix 1. Abbreviations....................................................................................................127
Appendix 2. Mayo Scoring System for Assessment of Ulcerative Colitis Activity..............131
Appendix 3. Glossary of Terms for Mayo Score Used in B7581002 Study..........................132
Appendix 4. Clinical Criteria for Diagnosing Anaphylaxis Guidance30................................133
Appendix 5. Protocol Specific Infliximab Biosimilars..........................................................134


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PROTOCOL SUMMARY
Background and Rationale:
Pfizer has exclusively in-licensed F8IL10 (Dekavil) from Philogen S.pA., Siena, Italy, for 
development in inflammatory disorders.  In nonclinical or clinical studies sponsored by 
Philogen or conducted using Philogen manufactured material, the product is identified as 
F8IL10.  In nonclinical and clinical studies conducted by or for Pfizer using Pfizer 
manufactured material, the investigational product is identified as PF-06687234.
PF-06687234 is comparable to F8IL10.
Interleukin-10 (IL-10) is a pleiotropic cytokine with wide-ranging effects on the anti and 
pro-inflammatory functions of both the innate and adaptive arms of the immune system.  
IL-10 can enhance T regulatory cell function, block dendritic cell maturation, and induce 
down-regulation of Th1 cytokines and major histocompatibility complex (MHC) class II 
antigens, and increase B cell survival, proliferation, and antibody production.  At the 
molecular level, IL-10 can modulate the NF-κB and janus kinase signal transducers and 
activators of transcription (JAK-STAT) signaling pathways.  A critical role for IL-10 in 
inflammatory bowel disease (IBD) pathophysiology is strongly supported by human genetics, 
as complete loss of IL10, IL10RA and IL10RB results in severe early onset IBD.4  Taken 
together, IL-10-based therapies could have significant utility in treatment of IBD.
PF-06687234 is a fully human single chain variable fragment (scFv)-cytokine fusion protein 
consisting of the scFv F8 (specific to the Extra-Domain A of fibronectin, selectively 
expressed in newly formed blood vessels during inflammatory responses) fused to the 
anti-inflammatory cytokine IL-10.  PF-06687234 is designed to enrich IL-10 delivery to 
inflamed tissues, potentially leading to higher local concentrations, greater clinical efficacy, 
and decreased systemic toxicity and is currently being investigated in subjects with ulcerative 
colitis (UC). 
Figure 1.
Structural Diagram of PF-06687234


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Objectives and Endpoints:
Primary Efficacy Objective(s):
Primary Efficacy Endpoint(s):

To evaluate the efficacy of PF-06687234 in induction 
of clinical remission in subjects with UC and a partial 
response to anti-TNF-.

Proportion of subjects in clinical remission at 
Week 12 (as defined by a modified total Mayo Score 
with a traditional endoscopic subscore 1, stool 
frequency subscore 1 and rectal bleeding 
subscore = 0).a
Primary Safety Objective(s):
Primary Safety Endpoint(s):

To evaluate the safety and tolerability of PF-06687234 
in subjects with UC and a partial response to 
anti-TNF-.

Incidence and severity of adverse events, serious 
adverse events and withdrawals due to adverse 
events, ECGs, vital signs and safety laboratory tests.
Secondary Objective(s):
Secondary Endpoint(s):

To evaluate the efficacy of PF-06687234 in induction 
of endoscopic improvement in subjects with UC and 
partial response to anti-TNF-.

To evaluate histological improvement in subjects with 
UC and partial response to anti-TNF-.

To evaluate the efficacy of PF-06687234 in induction 
of clinical response in subjects with UC and a partial 
response to anti-TNF-.

To describe the PK of PF-06687234 in subjects with 
UC.

To evaluate the immunogenicity of PF-06687234 in 
subjects with UC.

Proportion of subjects with endoscopic improvement 
at Week 12 (defined as decrease of 1 point in a 
modified endoscopic subscore or an absolute 
endoscopy score of 1).b

Mean change from baseline at Week 12 in Geboes
histology score.

Proportion of subjects with a clinical response at 
Week 12 defined with a decrease from baseline of at 
least 3 points in total Mayo score with at least 
30% change, accompanied by at least one point 
decrease or absolute score of 0 or 1 in rectal bleeding 
subscore.

Proportion of subjects with change from baseline in 
partial Mayo Score of 2 with no individual subscore 
>1 at Weeks 2, 4, 6, 8, 12.

Serum concentrations of PF-06687234.

Incidence of the development of HAFAs and Nabs
against PF-06687234.
Exploratory Objective(s):
Exploratory Endpoint(s):

To collect banked biospecimens and additional 
non-banked samples (eg, intestinal biopsies, stool for 
microbiome analysis, serum and plasma for analysis of 
proteins, whole blood for RNA analysis and 
epigenetics and/or cytometry) for exploratory research, 
unless prohibited by local regulations or ethics 
committee decision.

To evaluate disease pathway and related biomarkers 
(ie, hsCRP and fecal calprotectin).

To describe the full PK profile in a subgroup of 
subjects.

To evaluate tissue concentrations of PF-06687234 in 
biopsy samples.

Collection of banked biospecimens and additional 
non-banked samples (eg, intestinal biopsies, stool for 
microbiome analysis, serum and plasma for analysis 
of proteins, whole blood for RNA analysis and 
epigenetics and/or cytometry) unless prohibited by 
local regulations or ethics committee decision.  
Additional information on collection and potential 
use is provided in the Banked Biospecimens section.

Change from baseline in fecal calprotectin at 
Weeks 4, 8, 11.

Change from baseline in hsCRP at Weeks 4,8,11.

AUC(0-Tau), Cmax, Tmax, t1/2, CL/F, Vz/F.

PF-06687234 tissue concentration in inflamed and 
non-inflamed biopsies.


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PFIZER CONFIDENTIAL
Page 22
a.
The assessment of clinical remission will utilize the current definition of the traditional Mayo endoscopic subscore, 
which allows for assessment of mild friability in the subscore of 1. 
b.
The Central Readers for endoscopy Mayo subscores will also employ an assessment as to the presence or absence of 
any friability (including mild).  In this assessment the presence of any friability (including mild) will be scored as 2
(modified endoscopic subscore).  
Apparent clearance (CL/F), Apparent volume of distribution (Vz/F), Area under the concentration-time curve to the end 
of the dosing period (AUC(0-Tau)), Anti-tumor necrosis factor-(anti-TNF-), maximum observed concentration (Cmax) 
electrocardiogram (ECG), human anti-fusion antibody (HAFA), neutralizing antibodies (NAbs), pharmacokinectic (PK), 
ribonucleic acid (RNA), time to reach maximum concentration (Tmax), terminal half-life (t1/2).
Study Design and Treatments:
This is a Phase 2A, randomized, double-blind, placebo-controlled, parallel group, multicenter 
study in subjects with active UC and a non-remission response to infliximab.  Each subject 
will be randomly assigned to 1 of 2 treatment arms (1 active; 1 placebo) with approximately 
76 subjects in total (38 subjects per arm) enrolled for the study to achieve a total of 
64 evaluable subjects. 
Using the Mayo scoring definitions in Appendix 2 and Appendix 3, clinical remission in this 
protocol is defined as those subjects with a traditional endoscopic subscore of 0 or 1, stool 
frequency subscore of 0 or 1 and rectal bleeding subscore of 0.
Eligible subjects for enrollment will meet criteria for partial response to infliximab but in 
non-remission during screening, despite at least 14 weeks after initiation of infliximab 
therapy for active ulcerative colitis prior to study entry.
The duration of participation for eligible subjects will be approximately 26 weeks.  This will 
include a 4-week screening period, a 12-week investigational product treatment period, a 
4-week follow-up period and a telephone contact conducted 6-weeks after the follow-up 
visit.  During the treatment period subjects will visit the clinic every week (2 days) for 
subcutaneous (SC) administration of 20 mg of the investigator product (IP) for a total of 
12 visits.  In addition, all subjects enrolled in the study will be continuing treatment with 
their infliximab therapy as a background therapy during the study.  Subjects will be 
administered their infliximab therapy by intravenous (IV) administration at the clinic on 
Day 1, and subsequent doses appropriately at study visits based on the subject’s background 
dosing interval for infliximab.
Subjects will be required to return to the clinic for one visit 4 weeks after the last visit during 
the treatment period to evaluate for safety which will constitute an onsite follow-up visit.  
Subjects on infliximab every 8 weeks will also be administered infliximab therapy at this 
visit.  Subjects on infliximab every 6 weeks will require an additional site visit for 
administration of infliximab at Week 18.
There will be a telephone contact at Week 22 to confirm any serious adverse events (SAEs) 
have been reported to the sponsor and to provide results of Week 16 immunogenicity testing.


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Subjects with no detectable HAFA or NAb against IL-10 portion of PF-06687234 by the 
Week 16 visit will not require further follow-up beyond the Week 22 telephone contact.  
However, subjects with detectable HAFA or NAb against the IL-10 portion of PF-06687234 
at Week 16 will be informed of their immunogenicity status at the Week 22 telephone 
contact.  These subjects will be required to return for an onsite visit at Week 28 for repeat 
immunogenicity testing.  If these subjects have detectable HAFA or NAb against the IL-10 
portion of PF-06687234 from the immunogenicity sample collection at Week 28, they will 
require one additional follow-up collection 3 months after Week 28 at approximately 
Week 40.  
Statistical Methods:
This study employs a randomized parallel design with one treatment arm and one placebo 
arm.  The primary endpoint is clinical remission defined by the modified total Mayo score
with subscores of stool frequency 1, endoscopy scores 1 and rectal bleeding score of=0.  
The placebo and the treatment arm are assumed to have the remission rates as 22% and 52%.  
With one-sided alpha=0.05, to detect a treatment difference 30% in clinical remission 
64 (32*2) samples are needed to have 80% power.  Assuming 15% dropout rate, total 
76 subjects will be recruited in the trial.  Based on the recruitment rates, an interim analysis 
for futility based on conditional power less than 10% may be performed.
The primary endpoint will be analyzed using exact Chan and Zhang method22 and all other 
endpoint data will be analyzed using either the linear mixed model or the generalized linear 
mixed model.


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PFIZER CONFIDENTIAL
Page 24
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 table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
Enrollment Procedures
Informed consent
X
Inclusion/Exclusion 
Criteria
X
X
Demographics & 
Medical historyc
X
Vital Signs
Weight (lbs or kgs)d
X
X
X
X
X
X
Height (in or cm)d
X
BP and Pulse (after 
sitting for 
approximately 
5 minutes)e
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Temperature 
(C or F)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Medical Procedures
Complete Physical 
Examf
X
X
X
Targeted Physical 
Examf
X
X
X
X
X
X
ECG (12-lead)
X
X
X
X
Chest X-ray
X


PF-06687234
B7581002
Final Protocol Amendment 4, 10 April 2020
PFIZER CONFIDENTIAL
Page 25
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
Video Flexible 
Sigmoidoscopy or 
Colonoscopyg
X
X
Endoscopic tissue 
biopsies for 
exploratory mRNA, 
tissue protein, tissue 
concentration 
(PF-06687234), 
epigenetics and/or 
cytometry/microbiom 
and tissue histology 
(central reader)r
X
X
Disease Activity Assessments
Total Mayo Scoreh
X
X
Partial Mayo Scoreh
X
X
X
X
X
X
Bowel Movement 
eDiary Instructions 
and/or Reminder
X
X
X
X
X
X
X
X
X
X
X
X
X
Bowel Movement 
Diary Data (eDiary)i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Geboes score
X
X
UCEIS
X
X
Laboratory Assessments
Safety laboratory: 
Hematology, 
chemistry, UA
X
X
X
X
X
X
X
X
X
X
PT, PTT/INR
X
X
X
Serum pregnancy test 
or FSHj
X
Urine pregnancy testj
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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B7581002
Final Protocol Amendment 4, 10 April 2020
PFIZER CONFIDENTIAL
Page 26
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
Stool specimen for 
enteric pathogens to 
include C-Diff 
toxinsk
X
X
Serology: HIV, 
HBsAg, total 
HBcAb, HCVAb 
confirmed by HCV 
RNAl
X
Tuberculosis: PPD or 
IGRA per local 
guidelines (assayed 
at local lab if 
feasible)m
X
HbA1c
X
Pharmacodynamic (PD)
Serum for 
exploratory protein 
biomarkers
X
X
X
Blood for epigenetic 
testing of immune 
cells
X
X
X
Stool sample for 
fecal calprotectinq
X
X
X
X
Blood for gene 
expression profiling
X
X
X
X
Stool sample for 
exploratory 
biomarkers 
(microbiome)q
X
X
X
hsCRP
X
X
X
X


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Final Protocol Amendment 4, 10 April 2020
PFIZER CONFIDENTIAL
Page 27
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
Genomic banked 
biospecimens Prep 
D1n
X
Other 
exploratory/banked 
biospecimens (Prep 
B1.5, Prep B2.5, 
Prep R1)n
X
X
X
X
X
Pharmacokinetics (PK) and Immunogenicity
Serum PF-06687234 
concentrationo
X
X
X
X
X
X
X
Serum infliximab 
concentration for 
subjects on 
infliximab every 
8 weekst
Xs
Xt
Serum infliximab 
concentration for 
subjects on 
infliximab every 
6 weekst
Xs
Xt
Xt
HAFA and Nab 
against
PF-06687234p
X
X
X
X
X
X
Xv
ADA against 
infliximab for 
subjects on 
infliximab every 
8 weeksu
X
X


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Final Protocol Amendment 4, 10 April 2020
PFIZER CONFIDENTIAL
Page 28
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
ADA against
Infliximab for 
subjects on 
infliximab every 
6 weeksu
X
X
X
Treatment Procedures
Contraception check 
X













X
Randomization (after 
all screening 
procedures complete 
and eligibility 
confirmed)
X
Administration of 
PF-06687234 or 
Placeboy
X
X
X
X
X
X
X
X
X
X
X
X
Administration of 
Remicadeor 
protocol specific 
infliximab 
biosimiliar if on an 
every 8 week dosing 
interval for 
infliximab (See 
Appendix 5) 
Intravenous Infusiony
X
X
X


PF-06687234
B7581002
Final Protocol Amendment 4, 10 April 2020
PFIZER CONFIDENTIAL
Page 29
Screening
(-28 to -1)
Treatment Period
Follow-up
Study Visita
Screening
1
2
3
4
5 
6
7
8
9
10
11
12
13
14
15y (if 
applicable)
Telephone 
Contact
Study Week
Week -1 to 
-4
Week 
1
Week 
2
Week 
3
Week 
4
Week 
5
Week 
6
Week 
7
Week 
8
Week 
9
Week 
10
Week 
11
Week 
12/EWb
Week 
16
Week 
18
Week 
22
Study Day
-28 to -1
1
8
15
22
29
36
43
50
57
64
71
78
85
113
127
155
Visit Window
N/A
N/A
2 days based on Day 1x
Adminstration of 
Remicadeor 
protocol specific 
infliximab biosimilar 
if on an every 6 week 
dosing interval for 
infliximab (See 
Appendix 5) 
Intravenous Infusiony
X
X
X
X
Dispense Stool 
Collection Kit for 
Stool Specimen
X
X
X
X
X
Prior and 
Concomitant 
Medication(s) & 
Treatment(s)
X
X













Serious and 
non-serious adverse 
event monitoring
X















Xw
Disposition 
(Subject Status)
X
Abbreviations: ADA = anti-drug antibodies; BP = blood pressure; CRF = case report form; ECG = electrocardiogram; EW = Early Withdrawal; FSH = follicle 
stimulating hormone; IHC = immunohistochemistry; HAFA = Human Anti Fusion Antibody; 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; HEENT = head, eyes, ears, nose, 
throat; HIV = human immunodeficiency virus; hsCRP = high-sensitivity C-reactive protein; IGRA = interferon gamma release assay; INR = international 
normalized ratio; ISRs = Injection site reactions; PD = Pharmacodynamic; PK = Pharmacokinetics; PPD = purified protein derivative; PT = promthrombin time; 
PPT = partial thromboplastin time; SAE = serious adverse event; UA = urinalysis; UC = ulcerative colitis; WOCBP = woman of childbearing potential.
a.
Day relative to start of study treatment (Day 1).
b.
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.
c.
To include UC and smoking history.


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d.
Height and weight measured without shoes.
e.
At Day 1 and Week 1 BP and pulse will be collected approximately 30 minutes prior to dosing, approximately 30 minutes post dosing and approximately 
1 hour post dosing.  If subject experiences no safety issues (eg, severe injection site reactions, severe elevations BP and/or pulse) at Weeks 2-12 BP and 
pulse will be collected approximately 30 minutes prior to dosing and approximately 30 minutes post dosing.
f.
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.
g.
Flexible sigmoidoscopy or colonoscopy to be completed for a subject within approximately 14 days (preferably 5 to 7 days) prior to baseline visit 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.  The Partial 
Mayo score will be based on stool frequency, rectal bleeding and physician’s global assessment (refer to Appendix 2 and Appendix 3).  The total Mayo score 
at Week 0 will be calculated based on stool frequency, rectal bleeding and endoscopy performed during screening period and PGA obtained at baseline.
i.
The subject bowel movement diary to collect stool frequency and rectal bleeding should be collected daily using an electronic diary (e-Diary).
j.
Serum pregnancy testing at screening and urine pregnancy testing at other scheduled visits are required only for WOCBP.  FSH test to be performed at 
screening to confirm postmenopausal status in female subjects who have been amenorrheic for at least 12 consecutive months.  Note: If serum pregnancy test 
(for WOCBP) is borderline positive, the central lab will run an FSH test as a reflex test.
k.
To be performed locally if feasible 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 alternative.  During the treatment period only testing for C. difficile will be conducted at Week 12 visit.
l.
As per local regulations and 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.
m. To be assayed locally (IGRA assayed locally if feasible).  A documented negative PPD test within 12 weeks before screening is acceptable.  IGRA official 
reading and method of test must be located in the source documentation.
n.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a subject 
visit.
o.
Samples for serum PF-06687234 concentration should be collected approximately 30 minutes prior to dosing. See Section 6.2.11 for further details.
p.
Samples for HAFA and Nab against PF-06687234 will be collected prior to dosing for all the selected time points.
q.
Collection of stool for microbiome and fecal calprotectin analyses must be prior to administration of any bowel prep for endoscopy.
r.
At each biopsy collection time point, the 14 biopsies should be taken for the analyses described: 11 from abnormally inflamed colonic mucosa and 3 from 
normal appearing colonic mucosa in a targeted manner from the most affected area 15-30 cm from the anal verge in the colon.  See Section 7.3.2 for 
additional details.
s.
A sample will be collected for infliximab serum concentration at any time during the first screening visit.


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t.
Samples for trough serum infliximab concentration should be collected approximately 30 minutes prior to infliximab dosing. See Sections 6.2.8, 6.2.10, 
6.2.15 for additional details.
u.
Samples for ADA against infliximab will be collected prior to infliximab dosing.
v.
Subjects with no detectable HAFA or NAb against the IL-10 portion of PF-06687234 by Week 16 will not require further follow up beyond Week 22 
telephone contact.  Subjects with detectable HAFA or NAb against the IL-10 portion of PF-06687234 from the sample collection at Week 16 will be 
informed of their immunogenicity status at the Week 22 telephone contact and will be required to return for an onsite visit at Week 28 for repeat 
immunogenicity sample collection.  If these subjects have detectable HAFA or NAb against the IL-10 portion of PF-06687234 from Week 28 sample 
collection, they will require one additional follow up collection 3 months after Week 28 sample collection at approximately Week 40.  For early withdrawal 
subjects with detectable NAb against IL-10 of PF-06687432 and HAFA during the treatment period, their immunogenicity tests will be repeated at the 
Follow-up visit and approximately every three months for a maximum of 6 months from the follow-up visit until the level of NAb against the IL-10 portion 
of PF-06687432 and HAFA return to baseline level, or for 6 months, or stabilize at a level acceptable to the investigator and sponsor. At the discretion of 
the sponsor, the subjects with positive NAb against IL-10 may be tested for immunogenicity at shorter intervals (<3 months) or followed for longer than 
6 months duration.  
w.
Only SAEs will be collected on the CRF at the Week 22 telephone contact.
x.
At no point during the study can consecutive IP administration be given less than 4 consecutive days apart.  During the course of the study consecutive IP 
administrations within the same calendar week are not permitted on more than 3 occasions.
y.
Monitor for AEs and injection site reaction (ISRs).  Subjects should be monitored during and post Remicadeor protocol specific infliximab biosimilar (See 
Appendix 5) administration as per local standard of care and for a minimum of 1 hour following administration of PF-06687234 or placebo.  Subjects on an 
every 6 week infliximab dosing schedule will be administrated infliximab at Baseline, Week 6, Week 12 and Week 18. Administration of infliximab at 
Week 12 must be performed after all study safety and efficacy assessments are completed.  Subjects on an every 8 week infliximab dosing schedule will be 
administered infliximab at Baseline, Week 8, and Week 16. If applicable, Visit 15 (Week 18) is only for subjects on an every 6 week infliximab dosing 
schedule and not required for subjects on an every 8 week infliximab dosing schedule. Subjects may use infusion centers outside of study sites for 
administration of infliximab; however, they should report any AE or ISR related to infliximab infusion to the designated study site personnel.


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SCHEDULE OF ACTIVITIES Additional Pharmacokinetic Sub-study
Screening
Treatment Period
Follow-up
Study Visit
Screening
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Telephone 
Contact
Study Week 
Week -1 
to -4
Week
1
Week
2
Week 
3
Week
4
Week 
5
Week 
6
Week
7
Week
8
Week
9
Week
10
Week
11
Week
12/EWb
Week
16
Week 
22
Study Day
-28 to -0
1
1  
2
4
8 
15 
22 
29 
36 
43 
50 
57 
64 
71 
78
78 
79
81
85
113
155
Hours Post Last Dose
0
6 
(15 
min)
24
(3 
hr)
72
(7 
hr)
0
6 
(15 
min)
24 
(3 
hr)
72 
(7 
hr)
168 
Visit Window
Pharmacokinetics (PK) and Immunogenicity
Serum PF-06687234 
concentration
Xa
X
X
X
Xa
Xa
Xa
Xa
X
X
X
X
X
a.
Samples to be taken predose.
b.
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.


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1. INTRODUCTION
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal 
tract that affects five million people worldwide with considerable variability in incidence and 
prevalence by region.  The prevalence of IBD is highest in the second and third decade of life 
with another peak between 60 to 70 years of age.1 Ulcerative colitis (UC), one of two major 
phenotypes; the other is Crohn’s disease (CD), is characterized by continuous superficial 
mucosal inflammation that is localized to the colon and rectum.  UC involves a relapsing and 
remitting clinical course characterized by bloody diarrhea (with or without mucus), urgency, 
tenesmus, abdominal pain and weight loss, but can also present with variable extra intestinal
manifestations in the eye, skin, and joint compartments.2 There is also an increased risk of 
colorectal cancer in UC patients compared to the general population.  Given the chronic 
nature of the condition, patients experience poor health-related quality of life, and the direct 
and indirect costs of clinical management represent a significant economic burden to society.
The goal of current treatments is to achieve resolution of signs and symptoms of active 
disease (clinical remission) in the short term and to decrease the frequency of subsequent 
disease flares in the long term.  In the setting of moderate to severe UC, the treatment 
algorithm includes 5-aminosalicylates, corticosteroids, immunomodulators (primarily 
azathioprine and 6-mercaptopurine), and monoclonal antibodies against tumor necrosis factor 
(TNF)-or 47 integrin.  Anti-TNF-therapies (infliximab, adalimumab, and golimumab) 
are the most commonly used biologic agents to treat UC.  However, some patients do not 
achieve clinical remission with anti-TNF-therapy, and up to 50% will develop loss of 
response over time.3  In these patients, a dose escalation strategy with therapeutic drug 
monitoring (TDM) may be used to ensure adequate serum drug levels needed to achieve 
efficacy.  Another strategy is to explore the potential for additive benefit with the addition of 
another immunosuppressant as seen with the combination of infliximab with azathioprine in 
UC.15 However, such combinations targeting immune suppression are not without increased 
risk of serious infections and malignancies.  Consequently, safer and more efficacious 
approaches that combine other mechanisms of immune modulation are needed to improve 
therapeutic outcomes of existing therapies, offer additional options, and delay the need for 
surgical intervention, particularly in those with moderate to severe disease inadequately 
managed or refractory to standard treatments.
1.1. Mechanism of Action/Indication
Pfizer has exclusively in-licensed F8IL10 (Dekavil) from Philogen S.pA., Siena, Italy, for 
development in inflammatory disorders.  In nonclinical or clinical studies sponsored by 
Philogen or conducted using Philogen manufactured material, the product is identified as 
F8IL10.  In nonclinical and clinical studies conducted by or for Pfizer using Pfizer 
manufactured material, the investigational product is identified as PF-06687234.  
PF-06687234 is comparable to F8IL10.


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PF-06687234 is a fully human single chain variable fragment (scFv)-cytokine fusion protein 
comprised of the antibody fragment F8 and the anti-inflammatory cytokine interleukin-10 
(IL-10).  F8 is the scFv antibody fragment, which selectively binds to the splice variant of 
fibronectin Extra-Domain A (EDA), which is primarily expressed in newly formed blood 
vessels during inflammation.  The bioactive component of PF-06687234, IL-10, is a 
pleiotropic cytokine with wide-ranging effects on the anti - and pro-inflammatory functions 
of both the innate and adaptive immune system.  IL-10 can enhance T regulatory cell 
function, block dendritic cell maturation, and induce down-regulation of Th1 cytokines and 
MHC class II antigens, and increase B cell survival, proliferation, and antibody production.  
At the molecular level, IL-10 can modulate the critical NF-κB and JAK-STAT signaling 
pathways.  A critical role for IL-10 in IBD pathophysiology is strongly supported by human 
genetics, as complete loss of IL10, IL10RA and IL10RB results in severe early onset IBD.4  
Taken together, IL-10-based therapies could have significant utility in treatment of IBD. 
Figure 2.
Structural Diagram of PF-06687234
In fact, recombinant human (rh) IL-10 (Tenovil) has been examined in multiple autoimmune 
disorders, including CD.5 In the CD trial, Tenovil demonstrated clinical response, but not 
clinical remission, which could be attributed to the short half-life of Tenovil (~1.5 hours), 
insufficient tissue penetration, and/or short treatment duration.  Furthermore, dose-related
anemia and thrombocytopenia may have prevented exploration of potentially higher 
efficacious doses.
Unlike Tenovil however, PF-06687234 is designed (not yet proven clinically) to enrich IL-10 
delivery to inflamed tissues (eg, areas of active colitis), potentially leading to higher local 
concentrations and prolonged pharmacology, greater clinical efficacy, and decreased 
systemic toxicity.  The targeted IL-10 mechanism, intended to drive or restore 
anti-inflammatory pathways, presents a novel approach suitable for addition to existing 
treatments such as anti-TNF-agents that inhibit pro-inflammatory pathways but with 
limited benefit. 


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1.2. Background and Rationale
1.2.1. Drug Development Rationale
The etiology of UC remains complex and multifactorial, involving immune dysregulation, 
genetics, environmental factors, and microbiota.  Unlike conventional treatments such as 
corticosteroids and thiopurines that target broad immune suppression, current available 
biologic therapies target specific pro-inflammatory mediators - cytokines and integrins, to 
provide therapeutic benefit in some UC patients. 
Studies have shown that a large proportion of UC patients will not achieve remission or loss 
of remission to anti-TNF-therapy6,7,8 over time (secondary nonresponse).  In secondary 
nonresponders, dose adjustment through dose escalation or more frequent administration32-36
and combination with other agents have been considered to optimize response to treatment.  
Indeed, increased efficacy of infliximab has been shown in the UC SUCCESS study when 
used concurrently with azathioprine, in part likely due to the effect of an immunomodulator 
on anti-drug antibodies and therapeutic drug concentrations.9
Even with advances in biologic therapies for UC, a substantial proportion of moderate to 
severe UC patients do not achieve sustained clinical remission on these therapies, because of 
intolerance, lack of efficacy, and/or loss of efficacy.  There still remains a critical medical 
need for alternative treatments, approaches, and regimens to increase the proportion of 
patients with moderate to severe UC who can achieve long-term clinical remission, including 
complete mucosal healing.
The targeted pharmaco-delivery of cytokines by means of antibody cytokine fusion proteins
(ie, antibody-cytokine fusion proteins) has the potential to enhance therapeutic activity at the 
site of disease while sparing healthy tissues.  This approach has been extensively studied for 
various indications including different types of cancer but also chronic inflammatory 
conditions. 
The bioactive component of PF-06687234, IL-10, is a cytokine mainly produced by activated 
monocytes and T cells, which is deeply involved in the regulation of inflammatory responses 
and immune reactions. IL-10 has been considered an attractive candidate for therapeutic use 
in patients suffering from IBD. In fact, IL-10 seems to play a key role in these diseases, 
since IL-10 knock-out mice develop chronic enterocolitis.  Large multicenter trials in CD, 
testing multiple rhIL-10 (ilodecakin, Tenovil) dosages have been reported in subjects with 
mild/moderate or therapy-refractory CD,10,11 as well as in patients undergoing surgery to 
prevent postoperative recurrence.12 rhIL-10 treatment did not result in significantly higher 
remission rates or clinical improvement compared with placebo treatment13 and the 
development of rhIL-10 as a therapeutic drug for IBD was discontinued.  The authors 
concluded that the therapeutic action of systemically administered rhIL-10 is limited by 
pro-inflammatory effects of the cytokine and that this problem may be overcome by 
approaches that result in effective mucosal delivery without causing an increase in systemic 
IL-10 concentrations.14


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Consequently, the conjugation of IL-10 to the antibody fragment F8 potentially allows for the 
selective delivery of the cytokine to sites of inflammation.  In a mouse model of IBD, a 
significantly higher colon accumulation of 125I-F8IL10 was observed as compared with 
normal mice 24 hours after systemic administration demonstrating clear selective localization 
at sites of inflammation.
Unlike anti-TNF-biologic therapies, which rely on direct inhibition of pro-inflammatory 
cytokines, PF-06687234 is likely to exert beneficial clinical effects based on direct agonist 
effect through binding to IL-10 receptors by modulation of the innate and adaptive immune 
system towards restoring immune homeostasis.  In preclinical animal models, an additive 
and/or synergistic effect has been shown after concomitant administration of anti-TNF-and 
F8IL10, viral IL10 or rhIL-10.15,17,24 Therefore, additive or synergistic beneficial clinical 
effects may be possible with “add on” therapy of PF-06687234 to existing anti-TNF-
therapies. 
1.2.1.1. Non-Clinical Safety
The nonclinical toxicity studies were conducted with F8IL10 (Philogen sponsored) and 
PF-06687234 (Pfizer sponsored) in accordance with ICH S6(R1).  All pivotal studies in 
accordance with Good Laboratory Practice (GLP) were conducted in an Organization for 
Economic Co-operation and Development (OECD) mutual acceptance of data (MAD) 
compliant member state. As described in the current Investigator’s Brochure (IB), mice and 
cynomolgus monkeys were chosen as the nonclinical species based on their comparable
pharmacological properties to human. 
Nonclinical toxicity studies conducted with F8IL10 (Philogen sponsored) and PF-06687234 
(Pfizer sponsored) included repeat-dose studies with once or twice/weekly subcutaneous 
(SC) injection administration up to 8 weeks in duration in cynomolgus monkeys and up to 
6 months duration in mice with a 5 week recovery period.  PF-06687234 and its associated 
vehicle were tolerated when administered to rabbits as a single intravenous (IV) or peripheral 
venous (PV) dose (at 20.6 and 1 mg, respectively) followed by a 3-day observation period.  
There were no local irritation, macroscopic, or microscopic findings.  As is standard for 
therapeutic proteins, no genetic toxicity studies were conducted.  Safety pharmacology 
endpoints evaluated in mouse and cynomolgus monkey toxicity studies did not identify 
effects on the cardiovascular, central nervous or respiratory systems. 
To investigate safety effects related to serious infections, PF-06687234 (Dekavil) and 
PF-06410293, an anti-TNF-monoclonal antibody (adalimumab), were tested in panel of in 
vitro human immune function assays.  No additive or synergistic effect was observed in any 
assay when PF-06687234 and PF-06410293 were used in combination, relative to each 
investigational product alone.
Preliminary embryo fetal development studies up to 100 mg/kg/dose (200 mg/kg/week) of 
F8IL10 in pregnant mice and rabbits demonstrated no evidence of teratogenicity.


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Target organs were similar in mice and monkeys.  The predominant direct adverse effects 
(attributed to IL-10 pharmacology) were decreases in red blood cells (RBC) parameters 
(RBC count, hemoglobin, and hematocrit) and platelet counts.  Similar effects were observed 
previously with rhuIL-10 in monkeys.  At higher doses these hematological effects were 
associated with secondary effects related to systemic hypoxia and hemorrhage.  In monkeys, 
these hematologic findings increased in severity when the same total weekly dose was 
administered with a twice weekly dosing regimen versus once weekly dosing.  The 
hematological values returned to the normal range in both mice and monkeys at the end of 
the recovery phase.  Findings in the toxicity studies also comprised several investigational 
product-related effects attributed to an immunogenic response to a foreign protein.  These 
included a high incidence of anti-drug antibodies (ADAs) in mice (82-100%) and monkeys
(60-100%), associated with adverse clinical signs and mortality in mice consistent with 
anaphylaxis, injection site reactions, and microscopic findings in mice and monkeys 
consistent with immune complex deposition (ICD).  The latter included glomerulopathy and 
inflammatory cell infiltrates in multiple tissues characteristic of ICD including liver, 
epididymis, synovium, choroid plexus, and various other tissues.  ADA titers were still 
measurable after the recovery period and there was a range of full to partial recovery of 
effects attributed to ICD.
The no-observed-adverse-effect level (NOAEL) in mice in the 3 month study was 
20 mg/kg/week (twice weekly).  Excluding AEs secondary to immunogenicity, the 
20 mg/kg/week was the highest dose in the 6-month mouse study without adverse findings 
attributed directly to PF-06687234 and was associated with a safety margin of 3.2x compared 
to a clinical dose of 0.5 mg/kg/week on a body surface area basis.  The NOAEL in 
cynomolgus monkeys in the 8-week study was 9 mg/kg/week (weekly) and was associated 
with a safety margin of 5.8x compared to a clinical dose of 0.5 mg/kg/week on a body 
surface area basis.
In the toxicology studies, PF-06687234 serum concentrations were measurable on Day 1 but 
due to immunogenicity, limited serum PF-06687234 concentrations were detected after 
repeat administration.  Therefore, exposure obtained on Day 1 at the NOAEL doses in the 
above toxicity studies were considered as the NOAEL exposures.  In mice and cynomolgus 
monkeys the NOAEL exposures were associated with Cmax values of 5.51 g/mL and 
14.0 g/mL respectively.  The corresponding NOAEL Cav values were 0.913 g/mL and 
9.67 g/mL, respectively. 
The nonclinical safety program performed for this investigational product supports chronic 
dosing in clinical trials with inclusion of women of childbearing potential.
Please refer to the IB for more details on non-clinical safety information with PF-06687234.


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1.2.2. Previous Human Experience
Table 1.
Overview of F8IL10 and PF-06687234 Clinical Program (June 2018)
Study Protocol
Description
Study Duration
Dose/Regimen
Phase 0
11/203 
(Investigator-initiated 
research study by 
VUMC, Amsterdam)
Positron emission 
tomography (PET) study
Single dose
124I-F8IL10:
0.4 mg IV
Phase 1
PH-F8IL10-02/08
(Philogen-sponsored 
study)
Open label, 
uncontrolled, dose 
escalation, safety and 
pharmacokinetic study 
in RA subjects on 
background of MTX
8 weeks (4 weeks of 
mandatory and 
4 weeks of optional 
dosing)
F8IL10:
Weekly SC doses of 6, 15, 
30, 60, 110, 160, 210, 
300,450 and 600 g/kg 
(ie, 0.4 to 40 mg)
B7581001
(Pfizer-sponsored study)
Placebo-controlled, dose 
escalation, safety, 
tolerability, 
pharmacokinetic, and 
immunogenicity study in 
healthy adult subjects
Single dose
PF-06687234:
2 or 20 mga
(ie, 30 or 300 g/kg)
B7581003
(Ongoing Pfizer-
sponsored study)
Open-label, single IV 
dose of 
[124I]IB-PF-06687234 
and concurrent 
non-radiolabeled 
PF-06687234, PET-CT 
assessment in moderate 
to severe UC subjects
Single dose
PF-06687234: 7.4 mg
[124I]IB-PF-06687234: 1mg
Phase 2
PH-F8IL10-03/13
(Ongoing 
Philogen-sponsored 
study)
Placebo-controlled , 
double blind, efficacy 
and safety study in RA 
subjects on background 
of MTX
8 weeks
F8IL10:
Weekly SC dose of30 or 
160 g/kg
MTX = Methotrexate; RA = Rheumatoid arthritis; SC = Subcutaneous.
a. Doses >20 mg were not explored in healthy subjects in agreement with US FDA (as noted in 
Section 1.2.2.1).
1.2.2.1. Subject Disposition
As of June 2018, 48 subjects (including 8 healthy subjects, 38 rheumatoid arthritis (RA) and 
2 IBD subjects) have received at least one dose of either F8IL10 or PF-06687234 up to a 
maximum dose of 600 g/kg. Of these 48 subjects, 3 RA and 2 IBD subjects received a 
single tracer dose of 125I-F8IL10.


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Weekly doses of F8IL10 have been tested in RA subjects for up to 8 weeks 
(PF-F8IL10-02/08).  The formulation utilized in current Philogen studies is comparable to 
the formulation utilized in the Pfizer Phase 1 study.  This includes 5 subjects (3 RA and 
2 IBD) who received a single tracer dose of 125I-F8ILl10 in a PET study conducted at VU 
University Medical Center in Amsterdam (11/203). 
In the Philogen Phase 1 study (PH-F8IL10-02/08), RA subjects on background of 
methotrexate (MTX) were administered F8IL10 doses of 6, 15, 30, 60, 110, 160, 210, 
300,450 and 600 g/kg (ie, 0.4 to 40 mg) as a SC injection.  Thirty-five (35) RA subjects 
received at least one dose and 33 of 35 completed the mandatory 4 weekly cycles of
treatment.  One subject from the 450 g/kg cohort was discontinued from treatment due to 
purpura of lower limbs.  Twenty-four (24) out of 35 treated subjects completed the 
mandatory 4 weeks cycles and the 4 weeks of optional cycles, for a total of 8 weeks of 
exposure to the study drug.  
In the ongoing Philogen Phase 2 double-blind study in RA subjects on a background of MTX 
(PH-F8IL10-03/13) as of June 2018, 26 subjects have been enrolled and randomized to 
once-weekly 30 or 160 g/kg dose of F8IL10 or placebo.  The treatment duration for the 
study is 8 weeks.  Based on preliminary data, as provided by Philogen as of June 2018,
neither suspected unexpected serious adverse reactions (SUSARs) nor serious adverse events 
(SAEs) have been reported to date in this study. Immunogenicity assessment has been 
completed for the first 20 study subjects and did not reveal an antibody response specific to 
F8IL10. 
In the Pfizer Phase 1 study in healthy subjects (B7581001), 10 subjects received a single dose 
of either placebo (2 subjects), 2 mg (4 subjects) or 20 mg (4 subjects) of PF-06687234. All 
subjects completed the 28 day trial.  In this study, the US Food and Drug Administration
(FDA) only permitted dosing of healthy subjects up to a single SC dose of 20 mg of 
PF-06687234 due to the potential for neutralizing antibodies against endogenous IL-10, 
which places healthy subjects at risk to developing chronic enterocolitis.  Following 
determination that the risk-benefit did not support further dosing in healthy subjects, the 
Pfizer Phase 1 study (B7581001) was prematurely terminated per agreement with FDA and 
subsequent dosing planned in Phase 2 studies in UC subjects. It should be noted that no 
neutralizing antibodies against IL-10 have been observed with PF-06687234 to date.
1.2.2.2. Pharmacokinetic Results
PK profiles following F8IL10 and PF-06687234 have been characterized in RA 
(PH-F8IL10-02/08 Protocol) subjects and healthy subjects (B7581001). 
Following SC administration, the PK profiles of F8IL10 in RA subjects (n=3 per cohort) 
were atypical with a high degree of variability especially between 6 and 300 g/kg/week
(PH-F8IL10-02/08).  The PK exposures could not be characterized due to limited sampling 
time points, however Week 4 plasma trough samples were quantifiable for F8IL10 
suggesting a half-life (t½) longer than recombinant IL-10. 


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Additional PK samples were taken for the 450 (n=6) and 600 (n=3) g/kg/week cohorts 
Geometric mean of the maximum concentration (Cmax) and Cav (calculated as the area under 
the concentration curve from zero to 168 hours AUC0-168/168) on Week 1 for 
450 g/kg/week were 0.026 and 0.006 g/mL and for Week 4 were 0.014 and 0.0005 g/mL, 
respectively.  Similarly for the 600 g/kg/week dose level the Cmax and Cav for Week 1 were 
0.062 and 0.01 g/mL respectively and for Week 4 were 0.023 and 0.001 g/mL 
respectively.
The free IL-10 plasma profiles following PF-06687234 in healthy subjects (n=5, 4 active, 
1 placebo) were different from a typical SC route of administration for a non-targeted 
molecule but also showed a high degree of variability especially at the 2 mg dose.  Only one 
subject in the 2 mg dose cohort showed the typical profile expected from a SC administration 
with a half-life of approximately 48 hours.  The exposures following 20 mg PF-06687234 
were generally less variable compared to 2 mg.  The exposures showed a less than dose 
proportional increase between 2 and 20 mg.  The mean t½ for the 20 mg dose cohort was 
49.4 hours.  The observed Cmax and Cav (calculated as AUClast/168) for the 20 mg dose were 
0.0056 g/mL and 0.0027 g/mL, respectively, and well below the PK stopping limits of 
Cmax of 5.51 g/mL and Cav of 0.913 g/mL (NOAEL exposures for mice after single dose).  
Pharmacokinetic data should be interpreted with caution given limitations of the 
corresponding bioanalytical assay, as is described in the current Investigator’s Brochure (IB).
1.2.2.3. Immunogenicity Results
In RA subjects on the background of MTX (PH-F8IL10-02/08), using two different assays 
the total incidence rate for Human Anti Fusion Antibody (HAFA) was 17.6% (6 out of 
34 subjects).  No further testing was conducted for domain specificity and neutralizing 
antibodies.
In healthy subjects (B7581001), the HAFA incidence rate was 12.5% (1 out of 8 subjects).  
In this subject, HAFA developed at Day 28 post injection.  Another subject showed HAFA at 
pre-dose but did not show any treatment boosting following PF-06687234 administration.  
The HAFA for both subjects were non-neutralizing and were against the F8 portion of the 
molecule and not against IL-10. 
In the B7581001 study, there were no neutralizing antibody safety signals or dose-related 
laboratory abnormalities. 
1.2.2.4. Safety Results in Clinical Trials
IL-10, the bioactive moiety contained in the F8IL10 fusion protein, has been investigated 
extensively in clinical trials in healthy volunteers at single doses up to 100 g/kg 
administered IV27 and subjects suffering from several chronic inflammatory disorders, 
including psoriasis and CD.24,28
Please refer to the IB for more details on clinical safety information with PF-06687234.


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1.2.2.4.1. Safety Summary Philogen Phase 1 Study (PH-F8IL10-02/08)
In this study, there were no SAEs assessed as related to study drug, no SUSARs and no 
deaths reported, and no pattern of clinically significant vital sign changes.
Mild local injection site reactions (60%, 21 subjects) and anemia (5.7%, 2 subjects) were the 
most common adverse events (AEs) reported.  All of the injection site reactions were 
considered mild and disappeared (spontaneously or after a minor local treatment) within a 
few weeks after the end of treatment.  One non-study drug related SAE (hospitalization for 
moderate dyspnea) was reported in an RA subject dosed with 2 weekly doses of F8IL10 at 
450 g/kg concurrently with weekly 10 mg MTX subcutaneous injections.  In addition, this 
subject developed purpura on both legs (moderate severity and assessed as study drug 
related) which was classified as a dose limiting toxicity, per protocol, this same also 
developed thrombocytopenia with platelet count of 120,000/microliter (from 313,000 at 
baseline, assessed as study drug related) and increased alanine aminotransferase (ALT) (from 
21 IU/L at baseline to 112 IU/L at Week 3, assessed as study drug related).  This subject was 
hospitalized for 2 days and study treatment discontinued.  During the hospitalization, the 
investigator started treatment with methylprednisolone 20 mg twice daily and the subject was 
discharged from the hospital in good, general clinical condition with purpuric lesions 
considerably regressed and clear reduction of the subjective dyspnea.  Purpura, dyspnea, 
increased ALT and thrombocytopenia all resolved within 1 week after hospital discharge.
Three (3) patients (1 each in the 110 g/kg, 160 g/kg, and 450 g/kg cohorts) discontinued 
treatment due to persistence of injection site reaction; Grade 3 anemia and Grade 2 anemia 
respectively.  In addition, one patient was withdrawn from the study after Grade 2 dyspnea 
requiring hospitalization, which was assessed by the investigator as not related to the 
treatment and purpura which was assessed as possibly related to study treatment.
Anemia was reported as an AE in two subjects treated at the dosage of 160 g/kg and 
450 g/kg.  One (1) case of anemia was severe (decrease from baseline HGB of 2.1-2.9 g/dl 
or HGB <8, >7 g/dl) and the other moderate (decrease from baseline of 1.5-2.0 g/dl). In both 
of the anemia cases designated as an AE the events spontaneously resolved within 3-4 weeks 
after the interruption of study drug.
In 24/35 (68%) of the subjects a non-dose dependent HGB drop of at least 1 g/dl from 
baseline was observed.  In 9/35 (25.7%) of the subjects a moderate hemoglobin decrease 
from baseline was observed (1.5-2.0 g/dl) and in 7/35 (20%) of the subjects a severe decrease 
(2.1-2.9 g/dl from baseline or HGB <8, >7 g/dl) was observed.
1.2.2.4.2. Safety Summary Pfizer Phase 1 Study (B7581001)
PF-06687234 has been investigated in a double blind, placebo controlled, third party open 
(subject blind, investigator blind, sponsor open) Phase 1 study in healthy subjects 
(Protocol B7581001).  This study was designed to provide safety, tolerability, PK, and 
immunogenicity data by evaluating single SC dose, multiple SC dose and a single IV dose 
regimen of PF-06687234 in healthy subjects.  In the 2 completed single dose regimen cohorts 
(2 mg and 20 mg) with 4 active and 1 placebo treated subjects in each cohort, no SAEs were 


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reported.  Two subjects had mild headache (one in 2 mg cohort, one in placebo) and two 
subjects had mild injection site reactions (one treated with 2 mg, one with 20 mg).  No 
clinically significant trends in lab results were observed.  None of the subjects withdrew from 
study for treatment related AEs. 
1.3. Rationale
1.3.1. Study Rationale
This multicenter, two arm, Phase 2A study will be the first to assess PF-06487234 as add-on 
therapy to existing anti-TNF-(infliximab, IV) regimen in subjects with active UC.  The 
objectives of this study are to evaluate the efficacy (based on a modified Mayo score), safety, 
PK, immunogenicity, and tolerability of PF-06687234 at 20 mg SC administered once 
weekly for a total of 12 doses in subjects already being treated with infliximab infusions.
As previously noted (Section 1.2.1), optimizing infliximab dosing (adjusting either dosage 
and/or frequency) is an evidence-based recommendation for managing UC patients32-35 to 
achieve treatment targets.  Reducing the dosing interval to every 6 weeks has been shown to 
be safe and efficacious and is recommended36 to restore clinical response in UC patients in 
whom clinical benefit is attenuated after an initial response to infliximab. Routine clinical 
practice often employs a more frequent infliximab regimen than the every 8 weeks contained 
in the labeling for infliximab to keep UC patients in clinical response prior to switching to an 
alternative biologic if needed.  To align with current standard clinical practice, this study will 
allow subjects to continue on their stable existing infliximab regimen of either every 6 weeks 
or every 8 weeks as background infliximab treatment for UC.  The use of the every 6 week
regimen, consistent with current medical practice in the target population, does not alter the
risk:benefit in the study because:

Eligible participants continue on their stable background therapy, and 

No PK interaction affecting exposures is expected, and 

Close surveillance of the study participant for the duration of the study is part of the 
ongoing monitoring for an enrolled subject, and

Safe use of an every 6 week regimen has precedent in the label of infliximab for other
inflammatory conditions, such as ankylosing spondylitis.
The primary endpoint chosen is clinical remission based on a modified total Mayo score,
consistent with regulatory expectations for assessment of signs and symptoms using a 
patient-reported outcome and endoscopy.25,26  However, in this initial efficacy study,
assessment of clinical remission will utilize the current definition of the Mayo endoscopic 
subscore, which allows for assessment of mild friability in subscore of 1. 


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Preclinical studies in mice have indicated a potential additive or synergistic effect when an 
IL-10 fusion protein was combined with soluble TNF receptor15 (compared with either agent 
alone) in a murine model of arthritis.17,24  The combination of TNF-blocking agent and 
IL-10 has not been studied in a murine model of IBD. In earlier studies, recombinant mouse 
IL-10 or adenovirus encoding viral IL-10 and TNF-blocking agents were studied alone and 
in combination.  IL-10 in combination with an anti-TNF-antibody produced an additive 
therapeutic effect which demonstrated a greater duration of efficacy in a murine model of 
arthritis.24 Significant synergism was observed with the combination of vIL-10 and soluble 
tumor necrosis factor receptor immunoglobulin (sTNFR-Ig) in the collagen induced arthritis 
murine model utilized in this study.17 Collectively, these data suggest the potential for an 
additive or synergistic beneficial therapeutic effect on inflammation for IL-10 as add on 
therapy in humans under anti-TNF-.  A benefit-risk assessment is provided in Section 1.3.3. 
The current non-clinical toxicology package will support up to a 12-week treatment period
for the B7581002 study.  All sigmoidoscopy/colonoscopy videos will be read remotely by
central readers who will be blinded to study treatment.  A treatment period of 12 weeks of 
PF-06687234 or placebo dosing in addition to ongoing anti-TNF-regimen was chosen to 
allow for sufficient time for mucosal healing and symptom remission in the study population.  
Following completion of dosing at 12 weeks, the subjects will be followed for an additional 
4 weeks for further evaluation of safety.
During endoscopic evaluations, colon biopsies will be obtained and interrogated to provide 
evidence for pharmacologic modulation of the IL-10 pathway and to define parameters that 
might 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 the colon biopsies.
1.3.2. Dose Rationale
The proposed dosage for Study B7581002 is weekly SC administration of 20 mg 
(~300 g/kg) PF-06687234 for 12 weeks.  This dose level has been previously administered 
in the first in human (RA) study. 
F8IL10 or PF-06687234 has not been previously administered to UC subjects and currently 
no placebo-controlled efficacy data are available in RA.  Therefore, the dosage for Study 
B7581002 was selected on the basis of Tenovil (rhIL-10) data in CD with certain 
assumptions. In CD subjects, a non-monotonic dose response was observed for Tenovil 
where in a lower dose level showed clinical signals unlike the highest dose.10,11 Specifically, 
Tenovil administration at 5 g/kg/day10 for 28 days demonstrated clinical and endoscopic 
remission.  In another study in CD subjects, Tenovil administration at 8 g/kg/day11 for 
28 days showed clinical improvement.  In both studies the highest dose of 20 g/kg/day did 
not show the efficacy signals.  Tenovil administration in CD subjects led to dose related 
decreases in hematocrit and hemoglobin.5 The greatest decrease was observed at the 
20 g/kg/day dose. 


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Based on PK data from CD patients10 the estimated Cav in terms of free IL-10 concentrations 
following Tenovil administration at 5 g/kg/day and 10 g/kg/day were approximately 
0.5 and 2.0 ng/mL respectively.  Assuming that these concentrations associated with an 
efficacy response in CD subjects translate to UC subjects, the efficacious concentration range 
in UC was predicted as 0.5 to 2.0 ng/mL.  Assuming linearity in exposure for Tenovil 
between 10 and 20 g/kg/day doses, the corresponding IL-10 Cav for the 20 g/kg/day dose 
would be approximately 4.0 ng/mL.  The dosage for study B7581002 was therefore selected 
to achieve the target free IL-10 plasma concentrations between 0.5 and 2.0 ng/mL and avoid 
sustained concentrations above 4.0 ng/mL.  Observed plasma concentration data with 
F81L10 (PH-F8IL10-02/08 Protocol) and simulations using plasma data from the healthy 
subjects (Study B7581001) suggests that 20 mg SC (~300 g/kg to ~500 g/kg) administered 
weekly to UC subjects with weight >40 kg may achieve the targeted free IL-10 
concentrations. 
In summary, a weekly 20 mg (~300 g/kg to ~500 g/kg) PF-06687234 SC dose in subjects 
with weight >40 kg is: (a) expected to achieve concentrations equivalent to those observed to 
be efficacious with Tenovil, (b) anticipated to not be associated with significant decreases in 
hematocrit and hemoglobin levels, (c) has already been tested in humans (single dose healthy 
subjects and multiple dose in RA subjects) and is less than the highest dose level deemed safe 
and tolerated as monotherapy, albeit in a limited number of RA subjects, (d) has a 3.2-fold 
and 5.8-fold safety margin compared to the NOAEL doses from two mice studies (3 and 
6-month studies) and an 8-week cynomolgus monkey study compared with a clinical dose of 
0.5 mg/kg/week on a body surface area basis, and (e) is a reasonable target based on evidence 
of a non-monotonic dose response with Tenovil, which suggests a higher dose may not be 
necessarily beneficial. 
It is not expected that infliximab and PF-06687234 would have any significant 
pharmacokinetic drug-drug interaction requiring dosing adjustments.  Also in vivo, IL-10 did 
not have any significant effect on cytochrome activity and therefore PF-06687234 is not 
expected to have a drug-drug interaction with the concomitant medications31 expected in this 
study.
1.3.3. Summary of Benefit and Risks
IBD is a chronic inflammatory disease of the gastrointestinal tract.  The need for safer and 
more efficacious approaches that combine other mechanisms of immune modulation are 
needed to improve therapeutic outcomes of existing therapies and offer additional options, 
particularly in those who do not achieve clinical remission despite treatment.  IL-10 is a 
pleiotropic cytokine with wide-ranging effects on the anti- and pro-inflammatory functions of 
both the innate and adaptive arms of the immune system.  The rationale for IL-10 to treat 
IBD is supported by genetic evidence that complete loss of IL-10R1 and IL-10R2 causes 
severe colitis.20 In addition, genetic variation in other pathway members supports the IL-10 
agonist hypothesis as 17% of CD subjects have two (NOD2) mutations18,19 that can lead to 
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In vitro, PF-06687234 demonstrates potent IL-10 agonist activity in whole blood STAT1/3 
phosphorylation assays and shows potent inhibition of pro-inflammatory cytokine 
production.  In vivo, F8IL10 protected from weight loss and increases stool scores in a T-cell 
transfer mouse model of IBD and decreased disease related gene expression in the colon and 
pro-inflammatory cytokine levels in the serum.  Therapeutic treatment of F8IL10 in a mouse 
collagen induced arthritis model was able to stabilize clinical features of arthritis.  
Furthermore, in line with previous reports17,24 the combination of F8IL10 with a tumor 
necrosis factor (TNF) blocking agent (muTNFR-Fc) provided an additive and/or synergistic 
therapeutic effect on disease progression,15 providing a rationale for the use of PF-06687234 
as an add-on anti-TNF-biologics. The in vitro and in vivo nonclinical profiling supports 
the rationale that PF-06687234 is able to modulate disease activity and markers of 
inflammation and will represent a novel anti-inflammatory approach for the treatment of 
IBD.
Additional information for PF-06687234 may be found in the single reference safety 
document (SRSD), which for this study is the current Investigator’s Brochure. 
F8IL10 has been tested in a Phase 1 study (PH-F8IL10-02/08) at a maximum dose of 
600 g/kg/wk in RA subjects.  The active dose (approximately 300 g/kg or flat dose of 
20 mg SC) in this study is two-fold lower than the highest dose studied in RA Phase 1 high 
dose cohorts. This selected dose is expected to yield plasma concentrations between 0.5 and 
2.0 ng/ml. Due to the “leakiness” in the gut the plasma exposure of PF-06687234 in UC is 
not expected to be greater than that in RA.  Further IL-10 has been also administered as 
recombinant IL-10 (Tenovil) in CD and as pegylated IL-10 in cancer patients where mean 
serum IL-10 concentrations as of 6 ng/mL and 50 ng/mL have been reported respectively. 
Based on this data and clinical studies conducted to date, the dose of 300 to 500 g/kg/wk is 
expected to be well-tolerated. Further, no pharmacokinetic interaction is expected between 
infliximab and PF-06687234 that could lead to an increase in the exposure of either agent.  
Based on the evidence provided above for additive and/or synergistic therapeutic effect on 
disease progression, for the combined use of PF-06687234 with anti-TNF-biologics, the 
pharmacodynamics interaction between infliximab and PF-06687234 is hypothesized to be 
favorable.
While efficacy of PF-06687234 has yet to be investigated in clinical trials with UC subjects
(alone or as add on therapy to anti-TNF-standard treatment), recombinant human IL-10 
(Tenovil) as monotherapy demonstrated efficacy on secondary endpoints in trials with CD 
subjects.10,11  In addition, preclinical and genetic evidence provide a theoretical rationale that 
there is the potential for benefit in the UC patient population.
This study is investigating the administration of PF-06687234 concurrent to treatment with 
infliximab.  Combinations of biologics in a prior study with another anti-TNF-therapy, 
etanercept21 for treatment of RA resulted in higher rates of serious infections than in either 
individual biologic regimen.  In view of these data, the combination of infliximab with other 
biological therapeutics used to treat the same conditions as infliximab is not recommended in 
the labeling for infliximab.  However, it should be noted that unlike the previous intent to test 
combination of two immunosuppressive agents,21 in this study, the potential benefit of 


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PF-06687234 that is expected to modulate the innate and adaptive immune system towards 
restoring immune homeostasis (based on direct agonist effect through binding to IL-10 
receptors) will be explored in those who have not achieved clinical remission despite targeted 
immunosuppressive therapy with infliximab.  Although in vitro human immune function 
assays (viral T cell responses, monocyte/granulocyte phagocytosis and natural killer (NK)
cell assays) did not show any additive or synergistic effects with addition of PF-06687234 to 
adalimumab (another anti-TNF-agent) relative to each agent alone, the potential for 
additive or synergistic infection or other unexpected risks in the clinic cannot be completely 
excluded. 
It should be noted that in RA clinical trials to date conducted by Philogen, combination of 
weekly MTX, a broad immunosuppressant and weekly F8IL10 injections has not resulted in 
serious safety signal with dosing up to 8 weeks in duration. 
Further, in this study (B7581002), subjects will be required to come for weekly visits during 
the entire 12 week study active dosing period.  These frequent visits will allow for close 
monitoring including, weekly hematological parameters, targeted exams and vital sign 
assessments.  The protocol also includes immediate stopping rules for predefined criteria
(Section 6.4).  Randomized subjects with serious infections will be immediately discontinued 
from the study.  An internal review committee (Section 9.6), independent of the study team 
will also review the accumulating safety data and propose protocol changes to ensure subject 
safety.
Banked biospecimens will be collected for the purpose of conducting research; specific uses 
are described in the Banked Biospecimens section.  Comparing the deoxyribonucleic acid 
(DNA), ribonucleic acid (RNA), protein, and metabolite variation patterns of subjects who 
respond well and those who respond poorly to treatment may help to better define the most 
appropriate group of subjects in which to target a given treatment.  Collecting biospecimens 
for exploratory pharmacogenomic/genomic/biomarker analyses and retaining them in the 
Biospecimen Banking System (BBS) make it possible to better understand the investigational 
product’s mechanism of action and to seek explanations for differences in, for example, 
exposure, tolerability, safety, and/or efficacy not anticipated prior to the beginning of the 
study. 
Banked biospecimens retained in the BBS also can be used in research on IBD and other 
inflammatory diseases.
Providing these biospecimens is a required study activity for study sites and subjects, unless 
prohibited by local regulations or ethics committee (EC) decision. 
In summary, PF-06687234 has been generally safe and well tolerated in clinical studies to 
date.  While the therapeutic benefit has not been investigated, there is preclinical evidence 
that suggests subjects with UC may benefit from treatment with an IL-10 agonist added on to 
preexisting anti-TNF-therapy.  Potential risks of PF-06687234 include injection site 
reactions, anemia and thrombocytopenia.  Risks specific to combining PF-06687234 with 
infliximab at this time are not fully understood and may include increased risk of serious 


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infections.  Appropriate monitoring and stopping rules are proposed to manage and mitigate 
potential risks to subjects.  None of these effects preclude the continued exploration of safety, 
tolerability, PK, pharmacodynamics (PD) and efficacy in the intended patient population.
2. STUDY OBJECTIVES AND ENDPOINTS
Primary Efficacy Objective(s):
Primary Efficacy Endpoint(s):

To evaluate the efficacy of PF-06687234 in induction 
of clinical remission in subjects with UC and a partial 
response to anti-TNF-.

Proportion of subjects in clinical remission at 
Week 12 (as defined by a modified total Mayo Score 
with a traditional endoscopic subscore 1, stool 
frequency subscore 1 and rectal bleeding 
subscore = 0).a
Primary Safety Objective(s):
Primary Safety Endpoint(s):

To evaluate the safety and tolerability of PF-06687234 
in subjects with UC and a partial response to 
anti-TNF-.

Incidence and severity of adverse events, serious 
adverse events and withdrawals due to adverse 
events, ECGs, vital signs and safety laboratory tests.
Secondary Objective(s):
Secondary Endpoint(s):

To evaluate the efficacy of PF-06687234 in induction 
of endoscopic improvement in subjects with UC and 
partial response to anti-TNF-.

To evaluate histological improvement in subjects with 
UC and partial response to anti-TNF-.

To evaluate the efficacy of PF-06687234 in induction 
of clinical response in subjects with UC and a partial 
response to anti-TNF-.

To describe the PK of PF-06687234 in subjects with 
UC.

To evaluate the immunogenicity of PF-06687234 in 
subjects with UC.

Proportion of subjects with endoscopic improvement 
at Week 12 (defined as decrease of 1 point in a
modified endoscopic subscore or an absolute 
endoscopy score of 1).b

Mean change from baseline at Week 12 in Geboes 
histology score.

Proportion of subjects with a clinical response at 
Week 12 defined with a decrease from baseline of at 
least 3 points in total Mayo score with at least 
30% change, accompanied by at least one point 
decrease or absolute score of 0 or 1 in rectal bleeding 
subscore.

Proportion of subjects with change from baseline in 
partial Mayo Score of 2 with no individual 
subscore >1 at Weeks 2, 4, 6, 8, 12.

Serum concentrations of PF-06687234.

Incidence of the development of HAFAs and Nabs
against PF-06687234.
Exploratory Objective(s):
Exploratory Endpoint(s):

To collect banked biospecimens and additional 
non-banked samples (eg, intestinal biopsies, stool for 
microbiome analysis, serum and plasma for analysis of 
proteins, whole blood for RNA analysis and 
epigenetics and/or cytometry) for exploratory research, 
unless prohibited by local regulations or ethics 
committee decision.

To evaluate disease pathway and related biomarkers 
(ie, hsCRP and fecal calprotectin).

To describe the full PK profile in a subgroup of 
subjects.

To evaluate tissue concentrations of PF-06687234 in 

Collection of banked biospecimens and additional 
non-banked samples (eg, intestinal biopsies, stool for 
microbiome analysis, serum and plasma for analysis 
of proteins, whole blood for RNA analysis and 
epigenetics and/or cytometry) unless prohibited by 
local regulations or ethics committee decision.  
Additional information on collection and potential 
use is provided in the Banked Biospecimens section.

Change from baseline in fecal calprotectin at 
Weeks 4, 8, 11.


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biopsy samples.

Change from baseline in hsCRP at Weeks 4,8,11.

AUC(0-Tau), Cmax, Tmax, t1/2, CL/F, Vz/F.

PF-06687234 tissue concentration in inflamed and 
non-inflamed biopsies.
a.
The assessment of clinical remission will utilize the current definition of the traditional Mayo endoscopic subscore, 
which allows for assessment of mild friability in the subscore of 1. 
b.
The Central Readers for endoscopy Mayo subscores will also employ an assessment as to the presence or absence of 
any friability (including mild).  In this assessment the presence of any friability (including mild) will be scored as 2
(modified endoscopic subscore).  
Apparent clearance (CL/F), Apparent volume of distribution (Vz/F), Area under the concentration-time curve to the end 
of the dosing period (AUC(0-Tau)), Anti-tumor necrosis factor-(anti-TNF-), maximum observed concentration (Cmax)
electrocardiogram (ECG), human anti-fusion antibody (HAFA), neutralizing antibodies (Nabs), pharmacokinectic (PK), 
ribonucleic acid (RNA), time to reach maximum concentration (Tmax), terminal half-life (t1/2).
3. STUDY DESIGN
3.1. Study Overview
This is a Phase 2A, randomized, double-blind, placebo-controlled, parallel group, multicenter 
study in subjects with active UC and a non-remission (partial) response to anti-TNF-
therapy.  Each subject will be randomly assigned to 1 of 2 treatment arms (1 active; 
1 placebo) with approximately 76 subjects in total (38 subjects per arm) enrolled for the 
study to achieve a total of 64 evaluable subjects. 
Using the Mayo scoring definitions in Appendix 2 and Appendix 3, clinical remission in this 
protocol is defined as those subjects with a traditional endoscopic subscore of 0 or 1, stool 
frequency subscore of 0 or 1 and rectal bleeding subscore of 0.
Eligible subjects for enrollment will meet criteria for partial response to infliximab but in 
non-remission during screening, despite at least 14 weeks after initiation of infliximab 
therapy for active UC prior to study entry.
Women of childbearing potential (WOCBP) will be eligible for this study provided these 
women use two methods of contraception, as outlined in Section 4.4.1.


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Figure 3.
Study Design Schematic
3.1.1. Additional Pharmacokinetic Sampling
For most subjects participating in Study B7581002 a sparse PK sampling scheme will be 
followed.  As the PK of PF-06687234 in UC subjects has not been characterized, to better 
understand the PK of PF-06687234, a more extensive PK sampling scheme may be used in a 
subgroup of approximately 12 subjects who provide consent from any investigational site.  
For specific details refer to Section 7.5.2 regarding the additional PK sampling.
3.2. Duration of Subject Participation
The duration of participation for eligible subjects will be approximately 26 weeks.  This will 
include a 4-week screening period, a 12-week treatment period, a 10-week follow-up period 
which will include a telephone contact conducted 6-weeks after the onsite follow-up visit.  
During the treatment period subjects will visit the clinic every week (2 days) for SC 
administration of 20 mg of the investigator product (IP) or placebo for a total of 12 visits.  In 
addition, all subjects enrolled in the study will be continuing treatment with their infliximab 
therapy as a background therapy during the study. Subjects will be administered their 
infliximab at the baseline visit on study Day 1 and subsequent doses given at appropriate
study visits based on subject’s background dosing interval for infliximab.
Subjects will be required to return to the clinic for one visit 4 weeks after the last visit during 
the treatment period to evaluate for safety which will constitute an onsite follow-up visit.  
Subjects on infliximab every 8 weeks will also be administered their infliximab therapy at 
this visit.  Subjects on infliximab every 6 weeks will require an additional site visit for 
administration of their infliximab at Week 18. There will be a telephone contact conducted 
at Week 22 to confirm any SAEs have been reported to the Sponsor and to provide results of 
Week 16 immunogenicity testing.


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Subjects with no detectable HAFA or NAb against IL-10 portion of PF-06687234 by the 
Week 16 visit will not require further follow-up beyond the Week 22 telephone contact.  
However, subjects with detectable HAFA or NAb against the IL-10 portion of PF-06687234 
at Week 16 will be informed of their immunogenicity status at the Week 22 telephone 
contact.  These subjects will be required to return for an onsite visit at Week 28 for repeat 
immunogenicity testing.  If these subjects have detectable HAFA or NAb against the IL-10 
portion of PF-06687234 from the immunogenicity sample collection at Week 28, they will 
require one additional follow-up collection 3 months after Week 28 at approximately 
Week 40.  For early withdrawal subjects with detectable NAb against IL-10 of PF-06687432
and HAFA during the treatment period, their immunogenicity tests will be repeated at the 
Follow-up visit, and approximately every three months for a maximum of 6 months from the 
follow-up visit until the level of NAb against the IL-10 portion of PF-06687432 and HAFA
return to baseline level, or for 6 months, or stabilize at a level acceptable to the investigator 
and sponsor. At the discretion of the sponsor, the subjects with positive NAb against IL-10 
may be tested for immunogenicity at shorter intervals (<3 months) or followed for longer 
than a 6 month duration.
3.3. Approximate Duration of Study
Study enrollment is estimated to be completed in approximately 19 months.  The completion 
of the study is estimated to occur in approximately 26 months.
4. SUBJECT ELIGIBILITY CRITERIA
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.
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
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. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
3. Male and/or female subjects 18 years to 75 years of age and weight >40 kg at the 
time of informed consent. For subjects in South Korea: male and/or female 19 years 
to <70 years of age and weight >40 kg at the time of informed consent.


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4. A diagnosis of active UC (histologic) for 4 months.  A biopsy report supporting the 
diagnosis prior to the baseline visit must be available in the source documents.  In 
addition, a report documenting disease duration and extent of disease 
(eg, proctosigmoiditis, left-sided colitis, or pancolitis) based upon prior endoscopy 
must also be available in the source documentation.
5. Subjects who have partial response to anti-TNF (infliximab) and active UC as defined 
by (via screening endoscopy) a total Mayo Score 4 but 9 and an endoscopic 
subscore 2. Endoscopy (flexible sigmoidoscopy or colonoscopy), should be 
performed within 14 days of baseline (Day 1).  The endoscopic Mayo subscore 
assessed by the Central Reader must be available at the baseline visit.  The
assessment by the Central Reader will be used to derive the total Mayo score to 
determine study eligibility. Primary non-responder to anti-TNF therapy should be 
excluded.
6. UC extending at least 15 cm proximal to the anal verge at the time of the screening
endoscopy.  
7. Must be on a stable dose 5 to 10 mg/kg of Remicade, or protocol specified 
infliximab biosimilars (see Appendix 5) for a minimum of 14 weeks prior to study 
entry with no anticipation of need for change in infliximab treatment regimen
throughout the study (no switches from infliximab version at baseline to a different 
infliximab version will be permitted through Week 12).  For a subject who has 
recently switched dose or dosing intervals of infliximab during maintenance therapy, 
the subject must be on the same dose and dosing interval for at least two treatment 
cycles (minimum 12 weeks) before study entry. Subject must maintain the same
infliximab regimen of every 6 weeks or every 8 weeks throughout the study.  
8. Subjects currently receiving the following treatment for UC are eligible provided they 
have been on stable doses as described below:

Oral 5-aminosalicylic acid derivative (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 date of total 
Mayo Score assessment.

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 date of total Mayo Score assessment.  Decreases in steroid use due to AEs 
are allowed.

6-MP, azathioprine (AZA) (2.5 mg/kg), or MTX stable dose for 8 weeks prior to 
baseline. 


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9. Male subjects able to father children and female subjects of childbearing potential and 
at risk for pregnancy must agree to use two methods of contraception throughout the 
study and until the Week 16 visit (or 28 days after the last dose of IP). 

Women of childbearing potential (WOCBP) will be eligible provided these 
women use two methods of contraception throughout the study and until the 
Week 16 visit (or 28 days after the last dose of IP), as outlined in Section 4.4.

Female subjects of nonchildbearing potential must meet at least 1 of the following 
criteria:

Achieved postmenopausal status, defined as follows: cessation of regular 
menses for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed with a serum 
follicle-stimulating hormone (FSH) level confirming the postmenopausal 
state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure. 
All other female subjects (including female subjects with tubal ligations) are 
considered to be of childbearing potential. 
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and 
female subjects of childbearing potential who are unwilling or unable to use 
2 methods of contraception as outlined in this protocol for the duration of the study 
(Week 16 visit) or for at least 28 days after the last dose of investigational product.
2. Subjects with a diagnosis or documented history of total colectomy and/or pouchitis, 
indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation 
colitis, and diverticular disease associated with colitis, or clinical findings suggestive 
of Crohn’s disease (eg, fistulae, granulomas on biopsy).
3. Subjects considered in imminent need for surgery or with major elective surgery
(requiring general anesthesia) scheduled to occur during the study. 
4. Subjects with extensive colitis for at least 8 years who have not had a colonoscopy 
with surveillance biopsies within 2 years of the baseline visit.


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5. Subjects with history of or at screening endoscopy, biopsy documented colonic 
dysplasia or neoplasia.  Subjects with prior history of adenomatous polyps will be 
eligible if the polyps have been completely removed and pathology is negative.
6. Subjects who require infliximab dosing interval other than every 6 weeks or every
8 weeks during this study.
7. Subjects displaying clinical signs of fulminant colitis or toxic megacolon. 
8. Subjects with primary sclerosing cholangitis.
9. Subjects with known colonic stricture, or history of colonic or small bowel 
obstruction or resection.
10. Subjects with history of or current colonic or small bowel stoma.
11. History of known cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or 
any history of chronic anemia (HGB <10 g/dL) which is judged by the investigator to 
have an unclear specific etiology or is non self-limiting.
12. 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. 
13. Current evidence of active TB or latent TB infection or inadequately treated TB 
infection demonstrated by chest x-ray, a positive Mantoux (purified protein derivative 
[PPD]) tuberculin skin test or a positive Interferon Gamma Release Assay (IGRA to 
be tested at the site’s local lab) 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 should be used 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. 


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
If the results of the IGRA are indeterminate, the test may be repeated, and if a 
negative result is obtained, enrollment may proceed.  A positive test on repeat 
is exclusionary.

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).
14. Presence of active enteric infections (positive stool culture and sensitivity).  The 
presence of Clostridium difficile infection (reference C. diff section) or 
pseudomembranous colitis or history of recurrent Clostridium difficile infection.  
Known active invasive fungal infections such as histoplasmosis or parasitic 
infections. 
15. 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 and as per local regulations. 
16. Presence of transplanted organ; skin grafts are allowed. 
17. Previous severe hypersensitivity reaction to infliximab (Remicadeor infliximab 
biosimilar) or known hypersensitivity to inactive components of infliximab 
(eg, Remicadeor infliximab biosimilar) or to any murine protein.
18. Exposure to a live (attenuated) vaccine within 30 days prior to screening or 
anticipated need for any live (attenuated) vaccine during the study.
19. Significant concurrent medical condition at the time of baseline visit, including but 
not limited to the following:

Any major illness/condition or evidence of an unstable clinical condition 
(eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, 
pulmonary, immunologic [eg, Felty’s syndrome], neurologic 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.

Clinically significant infections within 6 months of baseline (eg, those requiring 
hospitalization or parenteral antimicrobial therapy, or opportunistic infections), 
history of any infection requiring antimicrobial therapy within 2 weeks of
baseline, or a history of any infection otherwise judged by the investigator to have 
the potential for exacerbation by participation 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).


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
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
(>450 msec in males and >470 msec in females).

Class III or Class IV heart failure.
20. 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.

Anti-integrin inhibitors (eg, vedolizumab) within 14 weeks prior to baseline.

Any prior use of natalizumab.

Interferon therapy within 8 weeks prior to baseline.

Subjects with prior treatment with lymphocyte-depleting agents/therapies 
(eg, CamPath[alemtuzumab], alkylating agents [eg, cyclophosphamide or 
chlorambucil], total lymphoid irradiation, etc).

Subjects who have received rituximab or other selective B lymphocyte-depleting 
agents within 1 year prior to baseline.

Subjects previously receiving leukocyte apheresis, including selective 
lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 
6 months of baseline. 

JAK inhibitors within 3 months prior to baseline.

Other investigational procedures(s) or product(s), such as immunomodulators
used in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or 
tacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.
21. Subjects with significant trauma or major surgery within 4 weeks of screening.
22. Prior evidence of liver injury or toxicity due to methotrexate.
23. History of sensitivity to heparin or heparin-induced thrombocytopenia. 
24. Abnormality in hematology and/or chemistry profiles during screening:


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
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) are excluded.  
Subjects with false positive anti-HBc may be enrolled based upon consultation 
with hepatologist confirming no infection with hepatitis B.

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; subjects with a history of Gilbert’s 
syndrome may have a direct bilirubin measured and would be eligible for this 
study provided the direct bilirubin is ULN.

HGB level 100 g/L (10.0 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 3.0 x 109/L (3000 cells/mm3) or absolute 
neutrophil count (ANC) <1200 cells/mm3 or absolute lymphocyte count of 
<0.5 x 109/L (<500 cells/mm3).

Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 based on the age 
appropriate calculation.

Glycosylated hemoglobin (HbA1C) >10%

Subjects with HbA1C > ULN without a diagnosis of diabetes mellitus should be 
evaluated prior to randomization for confirmation of diagnosis.

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. 
25. Donation of blood in excess of 500 mL within 8 weeks prior to baseline.
26. History of alcohol or drug abuse with less than 6 months of abstinence prior to 
baseline.
27. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
subjects who are Pfizer employees, including their family members, directly involved 
in the conduct of the study.
28. Participation in other studies involving investigational drug(s) within 30 days, or 
5 half-lives of investigational product (IP) (whichever is greater), prior to study entry 
and/or during study participation.


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29. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
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.
30. Known history of hypersensitivity, intolerance, or allergic reaction to PF-06687234 or
any constituent of the IP.
4.3. Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject eligibility 
criteria.  Subjects will have up to 4 weeks after the first screening visit to complete all 
screening procedures prior to randomization. 
A computer-generated randomization schedule will be used to assign subjects to the 
treatment groups.
4.4. Lifestyle Requirements
4.4.1. Contraception
All fertile male subjects and female subjects who are of childbearing potential as applicable 
to the study who are, in the opinion of the investigator, sexually active and at risk for 
pregnancy with their partner(s) must agree to use 2 methods of contraception (at least one of 
which is considered to be highly effective) consistently and correctly for the duration of the 
active treatment period and until Week 16 or 28 days after the last dose of investigational 
product.  The investigator or his or her designee, in consultation with the subject, will 
confirm that the subject has selected 2 appropriate methods of contraception for the 
individual subject and his or her partner from the permitted list of contraception methods and 
will confirm that the subject has been instructed in their consistent and correct use.  At time 
points indicated in the Schedule of Activities, the investigator or designee will inform the 
subject of the need to use 2 methods of contraception consistently and correctly and 
document the conversation and the subject’s affirmation in the subject’s chart (subjects needs 
to affirm their consistent and correct use of at least 2 of the selected methods of 
contraception).  In addition, the investigator or designee will instruct the subject to call 
immediately if 1 or both of the selected contraception methods is discontinued or if 
pregnancy is known or suspected in the subject or the partner. 
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:


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1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal) provided the subject or 
male subject’s female partner 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) or intrauterine system 
(IUS).
3. Male sterilization with absence of sperm in the post vasectomy ejaculate.
4. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
All sexually active male subjects must agree to prevent potential transfer to and exposure of 
partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for the duration of the active 
treatment period and until Week 16 or 28 days after the last dose of PF-06687234.
Male subjects must refrain from sperm donation for the duration of the active treatment 
period and until Week 16 or 28 days after the last dose of the investigational product.
4.5. 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.
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 product identifiers, subject study numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study. The contact number can also be used by investigator
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.


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5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator 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).
For this study, the investigational product is PF-06687234.
5.1. Allocation to Treatment
Allocation of subjects to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR].  The unblinded 
dispensing personnel will be required to enter or select information including but not limited 
to the user’s identification (ID) and password, the protocol number and the subject number.  
The unblinded dispenser will then be provided with a randomization number, treatment
assignment, and dispensable unit (DU) or container number when investigational product is 
being supplied via the IRT system.  The IRT system will provide a confirmation report 
containing the subject number, randomization number, and DU or container number 
assigned.  The confirmation report must be retained by the unblinded dispenser in the 
unblinded site files. 
The study specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system. 
5.2. Subject Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site.
5.3. Breaking the Blind 
The study will be subject, investigator and sponsor blinded.
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes should be 
broken only in exceptional circumstances when knowledge of the actual treatment code is 
essential for further management of the subject. If an investigator believes that immediate 
unblinding is necessary and time and circumstances allow, he/she is encouraged to discuss 
unblinding with a member of the study team.  However, discussion with a member of the 
study team in advance of unblinding is not required. When the blinding code is broken, the 
reason must be fully documented and entered on the case report form (CRF).


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5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
PF-06687234 will be supplied by Pfizer as a sterile lyophilized powder for solution for
injection.  Lyophilized investigational product vials contain a white uniform cake.  
PF-06687234 investigational product will be provided in dosage strength of 20 mg/vial in
single-use, sterile vials.  Placebo for PF-06687234 will also be provided by Pfizer as a sterile
liquid solution in single-use, sterile vials.
PF-06687234 and placebo are supplied in a 6 mL glass vial with a stopper and aluminum
overseal.  PF-06687234 investigational product is designed to be reconstituted with 1.3 mL
of sterile Water for Injection resulting in approximately 1 mL of extractable solution at
20 mg/mL.  The reconstituted solution for PF-06687234 has a nominal volume of 1.0 mL.  
PF-06687234 and placebo sterile vials will be supplied as individual vials for subsequent unit 
dosing preparation.  Both the IP and placebo vials will be provided to the site with open label 
packaging.
Infliximab allowed in this study is the innovator product REMICADEor protocol specific 
infliximab biosimilar approved for treatment of UC in the relevant geographic region (See 
Appendix 5).  Infliximab (REMICADEor protocol specific infliximab biosimilar) may be 
supplied by Pfizer (from commercial source) or by the clinical site conducting the study. All 
ancillary supplies, including sterile water for injection, used to prepare and administer doses 
will be provided by the clinical site conducting the study.
5.4.2. Remicadeor Protocol Specific Infliximab Biosimilar Label Instructions
All instructions, warnings and precautions, and adverse reactions associated with using 
infliximab can be found in the relevant geographic region RemicadePackage Insert or 
protocol specific infliximab biosimilar Package Insert (See Appendix 5).
5.4.3. Preparation and Dispensing
PF-06687234 lyophilized powder will be reconstituted using sterile water for injection.  The
PF-06687234 and placebo investigational products will be prepared at the investigational site
by two operators, both of whom are fully trained and experienced in aseptic technique and 
preparation and administration of solutions for subcutaneous use. Dose preparation must be 
performed with locally accepted aseptic handling technique.
See the Investigation Product (IP) Manual for instructions on how to prepare the
investigational products for administration. 
PF-06687234 and placebo will be prepared by qualified unblinded site personnel according 
to the IP manual.  
The investigational product will be administered in blinded fashion to the subject by the 
blinded site personnel. 


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5.5. Administration
IP dose may be temporarily withheld for a maximum of 14 consecutive days once during the 
treatment period at the discretion of the investigator. However, at no point during the study 
can consecutive IP administration be given less than 4 consecutive days apart.  During the 
course of the study consecutive IP administrations within the same calendar week are not 
permitted on more than 3 occasions.
During the study, Remicadeor protocol specific infliximab biosimilar (See Appendix 5) 
approved for treatment of UC will be administered as an IV infusion using a calibrated 
infusion pump by investigator site personnel on Day 1, Week 8 and Week 16 for a total of 
three doses for subjects on infliximab every 8 weeks, and Day 1, Week 6, Week 12 and 
Week 18 for subjects on infliximab every 6 weeks. Remicadeor protocol specific 
infliximab biosimilar administration should occur following most study procedures (except 
PF-06687234 administration) and must not be administered as an IV push or bolus.  The start 
and stop time of the infusion will be recorded on the CRF. No dose adjustment during the 
study will be permitted.
PF-06687234 will be administered as a 20 mg SC injection by the blinded investigator site 
personnel on Day 1, Week 1 (Day 8), Week 2 (Day 15), Week 3 (Day 22), Week 4 (Day 29), 
Week 5 (Day 36), Week 6 (Day 43), Week 7 (Day 50), Week 8 (Day 57), Week 9 (Day 64), 
Week 10 (Day 71) and Week 11 (Day 78) for a total 12 doses.  IP administration should 
occur following most study procedures as outlined in Schedule of Activities (SOA). 
The preferred body location for the SC injection is the abdomen: the 5 cm area around the 
navel should be avoided.  If abdominal injections are not possible, arm or thigh locations 
may also be used.  If an arm is used for the SC injection, the opposite arm should be used for 
the PK blood sample collections. 
Subjects should remain at the study site for a minimum of 1 hour for observation following 
PF-06687234 administration.  For subjects in the additional PK substudy, on Study Day 1 
and Study Day 78, the subject will remain at the site for a minimum of 1 hour for observation 
following PF-06687234 administration. After the 1 hour observation period, the subject may 
leave the study site as long as the subject agrees to return 5 hours later for collection of the
6 hour post investigational product PK sample.  
5.6. Injection/Infusion Discontinuation
Treatment of subjects with biologics 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 Remicadeor protocol 
specific infliximab biosimilar (See Appendix 5) as per standard of care and PF-06687234, for 
a minimum 1 hour after administration.


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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 criteria for further guidance regarding the 
diagnosis of anaphylaxis reactions (See Appendix 4).
If a subject experiences anaphylaxis, Remicadeor protocol specific infliximab biosimilar 
(See Appendix 5) and/or PF-06687234 administration (when possible) should be 
discontinued immediately and permanently (See Section 6.4).
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/injection should be 
stopped. 
In the event that symptoms are mild or minor in severity, at the discretion of the investigator, 
the infusion/injection may be restarted at a slower rate if symptoms are resolved within 
1 hour after the stop of infusion/injection.  If symptoms return, IP should be discontinued 
immediately and permanently. 
In the event that there is an infusion interruption, the entire duration of Remicadeor 
protocol specific infliximab biosimilar 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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5.7. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the label. 
See the IP manual for storage conditions of the product both prior to and following 
reconstitution.
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
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 investigational product receipt throughout the study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order. 
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery. The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer 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 products are briefly out of the temperature range described in the labeling are not 
considered excursions.


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5.8. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies, as the co-medication (Remicadeor 
protocol specific infiximab biosimilar).  All investigational products will be accounted for 
using a drug accountability form/record.
5.8.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.9. Prior Medication(s)
Any prior history (any time prior to signing the informed consent document (ICD) with no 
limitations of time) of corticosteroids, immunosuppressives (AZA, 6-MP, and MTX), and 
anti-TNF-biologics and anti-integrins will be recorded on the CRF.
Any prior UC medications taken within 90 days prior to screening must be recorded on the 
CRF.
All other medications taken within 4 weeks before the first dose of IP will be documented as 
prior medication(s).
5.10. Concomitant Medication(s) and Treatment(s)
All concomitant medication(s) and treatment(s) administered/taken during the study must be 
recorded with the indication, daily dose, start and stop dates of administration.  All subjects 
will be questioned about concomitant medication and treatment at each site visit.
Medication(s) administered/taken following the first dose of IP will be documented as 
concomitant medication(s).
5.10.1. Oral Corticosteroids Taken During the Study
Any oral corticosteroid(s) taken during the screening and treatment periods of the study will 
be captured on the appropriate CRF.
5.10.2. 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 total Mayo score assessment and through Week 16.  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 assessment.  Decreases in dose are 
allowed if due to AEs.


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
A stable dose of oral corticosteroid treatment (prednisone/equivalent up to 
20 mg/day; budesonide up to 9 mg/day) for at least 2 weeks prior to total Mayo score 
screening assessment and through Week 16.  If oral corticosteroids have been 
recently discontinued, they must have been stopped at least 2 weeks prior to total 
Mayo score screening assessment.  Decreases in steroid use due to AEs are allowed.

A stable dose of immunomodulators (6-MP, MTX or AZA 2.5 mg/kg) from baseline 
and through Week 16.  Decreases due to AEs are permitted.
5.10.3. Prohibited Medications
The following medications are prohibited for the specified time periods as described below:

Any non-infliximab iTNF treatment or biologic therapy within 24 weeks of screening 
visit.

Oral budesonide (>9 mg/day) or prednisone (>20 mg/day) or equivalent oral systemic 
corticosteroid 2 weeks prior to baseline and through Week 12.

Any live (attenuated) vaccines from 30 days prior to screening or anytime throughout 
the study.

IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid 
enemas/suppositories within 2 weeks prior to baseline and through Week 16.

Anti-integrin inhibitors (eg, vedolizumab) within 14 weeks prior to baseline and 
through Week 16.

Any use of natalizumab at any time.

Interferon therapy within 8 weeks prior to baseline and through Week 16.

Lymphocyte-depleting agents/therapies (eg, CamPath[alemtuzumab], alkylating 
agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc)
within 1 year of screening visit.

Rituximab or other selective B lymphocyte-depleting agents within 1 year prior to 
baseline and through Week 16.

Leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte 
apheresis, or plasma exchange within 6 months of baseline and through Week 16. 

Janus kinase (JAK) inhibitors within 3 months prior to baseline and through Week 16.

Any investigational procedures(s) or product(s), such as immunomodulators used in 
transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or tacrolimus).


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5.11. Rescue Medication
Rescue therapy should be provided by the investigator as deemed clinically appropriate.  
Subjects requiring rescue medication prior to the end of the study will be discontinued from 
IP (PF-06687234 or placebo) and will enter the follow-up period.  Subjects requiring rescue 
medication after Week 11 (after last IP administration) should also complete the follow-up 
period.
6. STUDY PROCEDURES 
6.1. Screening
After informed consent has been obtained, subjects have up to 4 weeks of a screening period 
to complete all of the screening procedures.  Subject’s eligibility for the study will be 
evaluated during this period based on medical history, physical examination, laboratory 
values, bowel movement diary data and additional tests.  To prepare for study participation, 
subjects will be instructed on the use of Lifestyle Requirements (see Section 4.4) and 
Concomitant Medications (see Section 5.10).
Screening laboratory tests with abnormal results may be repeated once to confirm abnormal 
results; the last value will be used to determine eligibility.  If results return to normal within 
the 4-week screening period, the subject may enter the study. 
Subjects who do not meet eligibility criteria (eg, screen fail) may be re-screened once (with a 
new screening number). 
The study investigator, or appropriate delegate at the site, will discuss with each subject the 
nature of the study, its requirements, risks and restrictions.  Written informed consent must 
be obtained prior to performing any protocol-specific procedures, including washout of 
prohibited medications.
The following procedures will be performed:

ICD.

Review of inclusion and exclusion criteria.

Demography, complete medical history (including UC and smoking).

Assessment of prior concomitant medications, including a complete history of all 
therapies for UC (eg, steroids, immunomodulators and/or anti-TNF-and 
anti-integrin treatment) received since diagnosis (including treatment response), and 
detailed UC medications (including dose, frequency, and route) taken within 90 days 
prior to the screening visit.  Complete history of all drugs (including nonprescription 
drugs, vitamins, and dietary or herbal supplements), taken within 4 weeks prior to 
screening procedures.


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
Vital signs measurements including sitting blood pressure (BP) and pulse (after
approximately 5 minutes of rest) and temperature (oral, tympanic or axillary).

Measurement of height (in or cm) and weight (lbs or kg) without shoes.

Complete physical examination.

Standard 12-lead ECG (See Section 7.2.9 and Schedule of Activities).

Chest x-ray (See Section 7.2.10 and Schedule of Activities).  Negative results must be 
documented prior to Baseline (Day 1) randomization.

Collect blood, urine and 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, urinalysis and 
prothrombin time (PT), partial thromboplastin time (PTT)/international 
normalized ratio (INR);

HbA1c;

Immunogenicity: HAFAs and NAb against PF-06687234;

PK sample: Serum infliximab concentration;

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) 
will be performed by the central laboratory and HIV as per local regulations and 
to be assayed locally. Confirmation and 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 7.2.6 for 
Clostridium difficile);

Stool specimen for exploratory biomarkers (microbiome) (prior to initiation of 
any bowel preparation for endoscopy);


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
Stool specimen for fecal calprotectin (prior to initiation of any bowel preparation 
for endoscopy);

Blood for gene expression profiling.

Subjects will be instructed on the use of the Bowel Movement Diary (e-diary) for 
daily collection.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

UC Assessments:

Endoscopy: All subjects may undergo either a colonoscopy or a video flexible 
sigmoidoscopy at the discretion of the investigator. Subjects who undergo 
colonoscopy do not require a separate sigmoidoscopy.  If subjects undergo a 
colonoscopy for screening, flexible sigmoidoscopy for exam at Week 12 is 
allowed;

Endoscopy (flexible sigmoidoscopy or colonoscopy) should be performed within 
approximately 14 days (preferably 5 to 7 days) of 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;

Geboes score provided by Central Reader;

Ulcerative colitis endoscopic index of severity (UCEIS) provided by Central 
Reader;

Endoscopic tissue biopsies for exploratory mRNA, tissue protein, tissue
concentration PF-06687234, tissue epigenetic and/or cytometry/microbiome and
tissue histology (central imaging reader) (See Section 7.3.2 and Schedule of 
Activities).

Contraception check.

Serious and non-serious adverse event monitoring.
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:


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
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.
6.2.1. Baseline – Day 1
The baseline visit must occur on the projected visit date within approximately 28 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 approximately 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 and urine samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only);

Collect genomic banked biospecimens.  If missed, collect at the next available 
time point when biospecimens are being collected in conjunction with a subject 
visit;

Collect other exploratory banked specimens (Prep B1.5, Prep B2.5, Prep R1);

PD Biomarkers: hsCRP;

Serum for exploratory protein biomarkers;

Blood for gene expression profiling;


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
Blood for epigenetic testing of immune cells;

Pre-dose PK: Serum PF-06687234 concentration should be collected 
approximately 30 minutes prior to dosing;

Immunogenicity: HAFAs and Nab against PF-06687234, and infliximab ADA.

UC Assessment: Provide PGA to obtain baseline total and partial Mayo score and 
review subject bowel movement e-diary data (See Sections 7.3.3, 7.3.4 and Schedule 
of Activities).

Review bowel movement e-diary completion instructions.

Review prior and concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Randomization/Dosing may occur after all screening procedures are completed and results 
reviewed.  Note for WOCBP, the urine pregnancy test must be negative prior to dosing.

Administer Remicadeas per instructions in relevant geographic region Remicade
Package Insert or protocol specific infliximab biosimilar (See Appendix 5) approved 
for the treatment of UC as per instructions in relevant geographic region infliximab 
biosimilar package insert and as described in Section 5.5.

Administration of PF-06687234 or placebo should occur approximately 1 hour but 
not exceed 3 hours after the completion of the administration of Remicadeor 
protocol specific infliximab biosimilar (See Appendix 5) approved for the treatment 
of UC and as described in Section 5.5. 

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes post dosing and approximately 1 hour post dosing of 
PF-06687234 or placebo.  If subject experiences no safety issues (eg, severe injection 
site reactions, severe elevations BP and/or pulse) at Weeks 2-12 BP and pulse will be 
collected approximately 30 minutes prior to dosing and approximately 30 minutes 
post dosing.

Monitor for AEs and injection site reaction (ISRs).  Subjects should be monitored 
during and post Remicadeor protocol specific infliximab biosimilar (See 
Appendix 5) approved for the treatment of UC administration as per local standard of 
care and for a minimum of 1 hour following administration of PF-06687234 or 
placebo.


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6.2.2. Additional PK Sampling Day 1, Day 2 and Day 4
Subjects who agree and provide consent will have the following additional PK samples 
collected post-dosing:

Serum PF-06687234 concentration sample collected approximately 6 hours 
(15 min), 24 hours (3 hours) and 72 hours (7 hours).
6.2.3. Week 1 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital signs measurement should 
occur approximately 30 minutes prior to dosing.

Collect blood and urine samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only);

Pre-dose PK: Serum PF-06687234 concentration sample should be collected 
approximately 30 minutes prior to dosing.

Review of bowel movement e-diary completion instructions (See Schedule of 
Activities).

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.


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
Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes post dosing and approximately 1 hour post dosing.  
If subject experiences no safety issues (eg, severe injection site reactions, severe 
elevations BP and/or pulse) at Weeks 2-12 BP and pulse will be collected 
approximately 30 minutes prior to dosing and approximately 30 minutes post dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour
following administration of PF-06687234 or placebo.
6.2.4. Week 2 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital signs measurement should 
occur approximately 30 minutes prior to dosing.

Targeted physical examination.

Collect blood and urine samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only);

Collect other exploratory banked specimens (Prep B1.5, Prep B2.5, Prep R1).

UC Assessment: Partial Mayo score and review subject bowel movement e-diary data 
(See Sections 7.3.3, 7.3.4 and Schedule of Activities).

Review bowel movement e-diary completion instructions.

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.


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
Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.5. Week 3 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital signs measurement should 
occur approximately 30 minutes prior to dosing.

Collect blood and urine samples for the following laboratory tests:

Urine pregnancy test (WOCBP only);

Pre-dose PK: Serum PF-06687234 concentration sample should be collected 
approximately 30 minutes prior to dosing;

Immunogenicity: HAFAs and Nab against PF-06687234.

Review of bowel movement e-diary completion instructions (See Schedule of 
Activities).

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).

Review concomitant medications/treatments.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Contraception check.

Serious and non-serious adverse event monitoring.


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Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.6. Week 4 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital signs measurement should 
occur approximately 30 minutes prior to dosing.

Record subject’s weight.

Targeted physical examination.

Collect blood, urine and 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 for exploratory protein biomarkers;

Stool sample for fecal calprotectin;

Blood for epigenetic testing of immune cells;

Blood for gene expression profiling;

Collect other exploratory banked specimens (Prep B1.5, Prep B2.5, Prep R1).


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
UC Assessment: Partial Mayo score and review subject bowel movement e-diary data 
(See Sections 7.3.3, 7.3.4 and Schedule of Activities).

Review bowel movement e-diary completion instructions.

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234.
6.2.7. Week 5 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital signs measurement should 
occur approximately 30 minutes prior to dosing.

Collect urine sample for the following laboratory tests:

Urine pregnancy test (WOCBP only).

Review of bowel movement e-diary completion instructions (See Schedule of 
Activities).

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).


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
Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.8. Week 6 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes prior to dosing. 

Targeted physical examination.

Standard 12-lead ECG (See Section 7.2.9 and Schedule of Activities).

Collect blood, urine and stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only).

UC Assessment: Partial Mayo score and review subject bowel movement e-diary data 
(See Sections 7.3.3, 7.3.4 and Schedule of Activities).

Review bowel movement e-diary completion instructions.


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
Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

If applicable, for subjects on an infliximab dosing schedule of every 6 weeks, collect 
a trough sample and an ADA sample for infliximab 30 minutes before administration 
of infliximab and administer Remicadeor protocol specific infliximab biosimilar 
(See Appendix 5) as per instructions in relevant geographic region Remicadeor 
protocol specific infliximab biosimilar Package Insert and as described in Section 5.5.

Administer PF-06687234 or placebo as described in Section 5.5 (Administration of 
PF-06687234 or placebo should occur approximately 1 hour but not exceed 3 hours
after the completion of the administration of Remicadeor protocol specific 
infliximab biosimilar (See Appendix 5) for subject with infliximab dosing every 
6 weeks).

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.9. Week 7 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes prior to dosing. 

Collect blood and urine samples for the following laboratory tests:

Urine pregnancy test (WOCBP only);


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
Pre-dose PK: Serum PK-06687234 concentration sample should be collected 
approximately 30 minutes prior to dosing;

Immunogenicity: HAFAs and Nab against PF-06687234, ADA against 
infliximab.

Review of bowel movement e-diary completion instructions (See Schedule of 
Activities).

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).

Review concomitant medications/treatments.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed. For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.10. Week 8 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes prior to dosing. 


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
Record subject’s weight.

Targeted physical examination.

Collect blood, urine and stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology, urinalysis and PT, 
PTT/INR;

Urine pregnancy test (WOCBP only);

PD Biomarkers: hsCRP;

Stool sample for fecal calprotectin;

Stool specimen for exploratory biomarkers (microbiome);

Collect other exploratory banked specimens (Prep B1.5, Prep B2.5, Prep R1).

UC Assessment: Partial Mayo score and review subject bowel movement e-diary data 
(See Sections 7.3.3, 7.3.4 and Schedule of Activities).

Review bowel movement e-diary completion instructions.

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

If applicable, for subjects on an infliximab schedule of every 8 weeks:

Collect a trough sample and an ADA sample for infliximab 30 minutes before 
administration of infliximab.

Administer Remicadeor protocol specific infliximab biosimilar (See 
Appendix 5) as per instructions in relevant geographic region Remicadeor 
protocol specific infliximab biosimilar Package Insert and as described in 
Section 5.5.

Administration of PF-06687234 or placebo should occur approximately 1 hour but 
not exceed 3 hours after the completion of the administration of Remicadeor 
protocol specific infliximab biosimilar (See Appendix 5) and as described in 
Section 5.5.


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
Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored as per local standard of 
care during and following administration of Remicadeor protocol specific 
infliximab biosimilar (See Appendix 5) and a minimum of 1 hour following 
administration of PF-06687234 or placebo.
6.2.11. Week 9 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes prior to dosing. 

Collect urine sample for the following laboratory tests:

Urine pregnancy test (WOCBP only).

Review of bowel movement e-diary completion instructions (See Schedule of 
Activities).

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.


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
Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.12. Week 10 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 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 and urine samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only).

UC Assessment: Partial Mayo score and review subject bowel movement e-diary data 
(See Sections 7.3.3, 7.3.4 and Schedule of Activities).

Review bowel movement e-diary completion instructions.

Review concomitant medications/treatments.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Contraception check.

Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.


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
Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.13. Week 11 (2 days)
There is a 2 day window for this study visit.  However, at no point during the study can 
consecutive IP administration be given <4 consecutive days apart.  During the course of the 
study consecutive IP administrations within the same calendar week are not permitted on 
more than 3 occasions.
Prior to dosing the following procedures will be completed:

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  Vital sign measurement should 
occur approximately 30 minutes prior to dosing. 

Collect blood, urine and stool sample for the following laboratory tests:

Urine pregnancy test (WOCBP only);

Pre-dose PK: Serum PF-06687234 concentration sample should be collected 
approximately 30 minutes prior to dosing;

Immunogenicity: HAFAs and Nab;

PD Biomarkers: hsCRP;

Stool sample for fecal calprotectin;

Stool specimen for exploratory biomarkers (microbiome).

Review bowel movement e-diary completion instructions.

Review subject bowel movement e-diary data (See Section 7.3.4 and Schedule of 
Activities).

Review concomitant medications/treatments.

Dispense labeled stool container and plastic bag (for refrigerated or frozen stool 
sample at subsequent visit).

Contraception check.


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
Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

Administer PF-06687234 or placebo as described in Section 5.5.

Measure vital signs including sitting BP and pulse (after approximately 5 minutes of 
rest) and temperature (oral, tympanic or axillary).  If subject experiences no safety 
issues then vital sign measurement should occur approximately 30 minutes post 
dosing.

Monitor for AEs and ISRs.  Subjects should be monitored for a minimum of 1 hour 
following administration of PF-06687234 or placebo.
6.2.14. Additional PK Sampling Week 11 (Day 78), Day 79 and Day 81
Subjects who agree and provide consent will have the following additional PK samples 
collected post-dosing:

Serum PF-06687234 concentration sample collected approximately 6 hours 
(15 min), 24 hours (3 hours) and 72 hours (7 hours).
6.2.15. Week 12 (2 days)/Early Withdrawal Visit
For subjects who discontinue early from the double-blind period prior to Week 12 visit, the 
procedures scheduled for Week 12 should be performed as an early withdrawal visit as soon 
as possible and then subjects should enter the follow up period.
There is a 2 day window for this study visit.

Measure vital signs including sitting BP and pulse (after approximately 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.

Complete physical examination.

Standard 12-lead ECG (See Section 7.2.9 and Schedule of Activities).

Collect blood, urine and stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology and urinalysis;

Urine pregnancy test (WOCBP only);

Stool sample for C-Difficile;


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
Serum for exploratory protein biomarkers;

Blood for gene expression profiling;

Blood for epigenetic testing of immune cells;

Collect other exploratory banked specimens (Prep B1.5, Prep B2.5, Prep R1);

PK: Serum PF-06687234 concentration sample should be collected;

Immunogenicity: HAFAs and Nab against PF-06687234.

UC Assessments:

Review subject bowel movement e-Diary data;

Endoscopy (video flexible sigmoidoscopy or colonoscopy as preferred by the 
investigator);

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, 7.3.4 and Schedule of Activities);

Geboes provided by Central Reader;

UCEIS provided by Central Reader;

Endoscopic tissue biopsies for exploratory mRNA, tissue protein, tissue 
concentration PF-06687234, tissue epigenetics and/or cytometry/microbiome and 
tissue histology (central imaging reader) (See Section 7.3.2 and Schedule of 
Activities).

Review concomitant medications/treatments.

Contraception check.

Serious and non-serious adverse event monitoring.

If applicable, for subjects on an infliximab dosing schedule of every 6 weeks, perform 
the following procedures after all other study specified procedures for the visit are 
completed:

Collect a trough sample and an ADA sample for infliximab 30 minutes before 
administration of infliximab;


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
Administer Remicadeor protocol specific infliximab biosimilar (See 
Appendix 5) as per instructions in the relevant geographic region Remicadeor 
protocol specific infliximab biosimilar Package Insert and as described in 
Section 5.5;

Measure vital signs including sitting BP and pulse (after approximately 5 minutes 
of rest) and temperature (oral, tympanic or axillary).  If subject experiences no 
safety issues then vital sign measurement should occur approximately 30 minutes 
post dosing;

Monitor for AEs and ISRs.  Subjects should be monitored as per local standard of 
care during and following administration of Remicade.
6.2.16. Week 16 Onsite Follow-up (+2 days)
There is a 2 day window for this study visit.
Follow-up contact will be completed at least 28 calendar days after the last IP administration 
to capture any potential adverse events (see Section 8.1.4) and to confirm appropriate 
contraception usage (see Section 4.4.1). 
The following procedures will be performed:

Measure vital signs including sitting BP and pulse (after approximately 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.

Complete physical examination.

Standard 12-lead ECG (See Section 7.2.9 and Schedule of Activities).

Collect blood, urine and stool samples for the following laboratory tests:

Safety laboratory tests for blood chemistry, hematology, urinalysis and PT, 
PTT/INR;

Urine pregnancy test (WOCBP only);

PK: Serum PF-06687234 concentration sample should be collected;

Immunogenicity: HAFAs and NAbs against PF-06687234.

Review concomitant medications/treatments.

Contraception check.


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
Serious and non-serious adverse event monitoring.
Dosing may occur after all pre-dosing procedures are performed.  For WOCBP, the urine 
pregnancy test must be negative prior to dosing.

If applicable, for subjects with an infliximab dosing schedule of every 8 weeks, 
administer Remicadeor protocol specific infliximab biosimilar (See Appendix 5) as 
per instructions in the relevant geographic region Remicadeor protocol specific 
infliximab biosimilar Package Insert and as described in Section 5.5.

Monitor for AEs and injection site reaction (ISRs).  Subjects should be monitored as 
per local standard of care during and following administration of Remicadeor 
protocol specific infliximab biosimilar (See Appendix 5).
6.2.17. If applicable, Week 18 (2 day) for Subjects on Infliximab Dosing Every 
6 Weeks
There is a 2 day window for this study visit.  Subjects may use infusion centers outside of 
study sites for administration of infliximab; however, they should report any AE or ISR 
related to infliximab infusion to the designated study site personnel.
The following procedures will be performed:

For subjects on an infliximab dosing schedule of every 6 weeks, administer 
Remicadeor protocol specific infliximab biosimilar (See Appendix 5) as per 
instructions in the relevant geographic region Remicadeor protocol specific 
infliximab biosimilar Package Insert and as described in Section 5.5.

Monitor for AEs and injection site reaction (ISRs). Subjects should be monitored as 
per local standard of care during and following administration of Remicade.
6.2.18. Week 22 Telephone Contact (+2 days)
After the Week 16 visit, one telephone contact will take place within 42 days to capture any 
potential SAEs (see Section 8.1.4), inform subjects of their immunogenicity status and 
complete the study disposition CRF (Subject status). Only SAEs will be collected on the 
CRF at the Week 22 telephone contact.
Subjects with no detectable HAFA or NAb against the IL-10 portion of PF-06687234 will 
require no further follow-up beyone the Week 22 telephone contact.  However, subjects with 
detectable HAFA or NAb against the IL-10 portion of PF-06687234 will be required to 
return for an onsite visit at Week 28 for repeat immunogenicity testing.  If these subjects 
have detectable HAFA or NAb against the IL-10 portion of PF-06687234 from the 
immunogenicity sample collection at Week 28, they will require one additional follow-up 
collection 3 months after Week 28 at approximately Week 40.


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Note:  Unscheduled visits should be arranged when possible in the event of an SAE, 
hospitalization and/or surgery, specified lab abnormalities or at discretion of investigator.
6.3. Subject Withdrawal
6.3.1. Withdrawal of Consent
Subjects who request to discontinue receipt of study treatment will remain in the study and 
must continue to be followed for protocol specified follow-up procedures; the follow-up visit 
should occur 4 weeks after their last dose whenever possible. The only exception to this is 
when a subject specifically withdraws consent for any further contact with him or her or 
persons previously authorized by the subject to provide this information. Subjects should 
notify the investigator in writing of the decision to withdraw consent from future follow-up, 
whenever possible. The withdrawal of consent should be explained in detail in the medical 
records by the investigator, as to whether the withdrawal is only from further receipt of
investigational product or also from study procedures and/or post-treatment study follow-up, 
and entered on the appropriate CRF page. In the event that vital status (whether the subject is 
alive or dead) is being measured, publicly available information should be used to determine 
vital status only as appropriately directed in accordance with local law.
6.3.2. Lost to Follow-up 
All reasonable efforts must be made to locate subjects to determine and report their ongoing
status. This includes follow-up with persons authorized by the subject as noted above. Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter. All attempts should be documented in the subject’s medical records. If it is 
determined that the subject has died, the site will use locally permissible methods to obtain 
the date and cause of death. If the investigator’s use of a third-party representative to assist 
in the follow-up portion of the study has been included in the subject’s informed consent, 
then the investigator may use a sponsor-retained third-party representative to assist site staff 
with obtaining the subject’s contact information or other public vital status data necessary to 
complete the follow-up portion of the study. The site staff and representative will consult 
publicly available sources, such as public health registries and databases, in order to obtain 
updated contact information. If, after all attempts, the subject remains lost to follow-up, then 
the last-known-alive date as determined by the investigator should be reported and 
documented in the subject’s medical records.
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 (see also the 
Withdrawal From the Study Due to Adverse Events section) 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 


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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 adverse events (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.
6.4. Guidelines for Monitoring and Discontinuations
The following laboratory abnormalities require monitoring and re-testing ideally within 
1 week:

Absolute neutrophil counts <1.2 x 109/L (<1200/ mm3).

Platelet counts <100 x 109/L (<100,000/mm3).

Any single AST and/or ALT elevation 3 times the upper limit of normal (repeat 
laboratory testing should include albumin, creatine kinase, total bilirubin, direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), PT [prothrombin time] with 
INR [international normalized ratio], and alkaline phosphatase), regardless of the total 
bilirubin.  (Please note that 3 times the upper limit of normal increases in ALT, AST 
need confirmation on separate blood draw before undertaking thorough evaluation for 
liver injury).

For women of child-bearing potential with any positive urine beta-human chorionic 
gonadotropin (-hCG) test, the subject will have study drug interrupted and a serum 
sample submitted to the central laboratory for -hCG testing.
Treatment with investigational product will be discontinued for:

Serious infections defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy, hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as serious adverse event (See 
Section 7.2.1).

Serious signs/symptoms of injection or infusion reactions (See Section 5.6).

Two sequential absolute neutrophil counts <1.0 x 109/L (<1000/mm3).

Two sequential hemoglobin values of <8.0 g/dL; <4.96 mmol/L; <80 g/L.

Any anemia requiring a blood transfusion.

Two sequential platelet counts <75 x 109/L (<75,000/mm3).

Two sequential lymphocyte counts <500/mm3; <0.5x109/L.


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
AST or ALT elevation >8 times the upper limit of normal.

Two sequential AST or ALT elevation 3 times the upper limit of normal with at 
least one total bilirubin value 2 times the upper limit of normal.

AST or ALT elevation 3 times the upper limit of normal combined with any one or 
more of the following; new onset of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash and/or eosinophilia >5%, or INR >1.5.

Two sequential AST or ALT elevation 5 times the upper limit of normal, regardless 
of total bilirubin or accompanying signs or symptoms.

Female subjects found to be pregnant during the study.

At the discretion of the PI, initiation of any new treatment for UC for disease 
progression.

Surgery for UC.

Other treatment related serious or severe AEs, after consultation with the Pfizer 
medical monitor or designee.

Detected neutralizing antibody to IL-10 domain of the IP during the study.
In the event that 2 subjects on IP develop the same AE MEDRA Preferred Term graded as 
severe intensity as defined in Section 8.3 or if 1 subject develops an SAE as defined in 
Section 8.2.3, and the event(s) are assessed as potentially causally related to the IP and not 
clearly related to the underlying disease process or other causes, an ad-hoc internal review 
committee (IRC) meeting will be convened. At this time the IRC will make 
recommendations to the study team.  These recommendations will be to stop the study, 
continue with modifications or continue with the study unchanged.
In addition, the Sponsor will notify all relevant regulatory authorities that such an ad-hoc 
IRC has been convened and will provide case details to all relevant regulatory authorities 
within 15 days of making the determination to convene the IRC meeting.
For early withdrawal subjects with detectable NAb against IL-10 of PF-06687432 and HAFA 
during the treatment period, their immunogenicity tests will be repeated at the Follow–up 
visit, and approximately every three months for a maximum of 6 months from the follow-up 
visit until the level of NAb against the IL-10 portion of PF-06687432 and HAFA return to 
baseline level, or for 6 months, or stabilize at a level acceptable to the investigator and 
sponsor. At the discretion of the sponsor, the subjects with positive NAb against IL-10 may 
be tested for immunogenicity at shorter intervals (<3 months) or followed for longer than 
6 months duration.


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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 manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Blood Volume
Total planned blood sampling for an individual subject that completes all currently scheduled 
assessments through Week 16 visit is approximately 400 mL.  Additional blood samples may 
need to be taken at times not specified in the protocol (eg, replacement of clotted or 
compromised specimens or repeat clinically significant out of range laboratory results).
7.2. Safety
7.2.1. Infections
A subject who experiences a serious infection as defined in Section 6.4 should be 
discontinued from the study.  A serious infection should be reported as an SAE and should be 
listed as the reason for discontinuation in the CRF.  All serious infections occurring during 
the study should undergo appropriate laboratory investigations, including culture, and the 
results (eg, any identified organisms or absence of growth) be recorded in the CRF.
Subjects who experience non-serious infections that require treatment may have their study 
drug temporarily discontinued during treatment at the investigator’s discretion.  Consultation 
with the Pfizer medical monitor is available.  Temporary discontinuation of study drug 
should be recorded in the CRF. 
7.2.2. Laboratory
The following safety laboratory tests will be performed at times as defined in the Schedule of 
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Table 2.
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)
Reticulocytes (% and 
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 sample to detect 
enteric infections and C. 
difficile toxins A and B
Stool sample for fecal 
calprotectin
Stool sample for 
exploratory biomarkers 
(microbiome)
Exploratory samples 
(serum, plasma, blood, 
RNA, DNA)
Colonic tissue biopsies
Systemic PF-06687234 
and infliximab
concentrations
HAFA and Nab
ADA against infliximab
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. Sponsor may request 
spot urine protein creatinine ratio for quantification if significant proteinuria is identified.
d.
In females who are amenorrheic for at least 12 consecutive months.
e.
Complete at screening.
f.
Serum/Urine for women of childbearing potential.  Serum pregnancy test must be performed at 
screening.  If serum pregnancy test (for WOCBP) is borderline positive, the central lab will run a FSH 
test to confirm menopause.
7.2.3. 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, prior to investigational 
product administration at the baseline visit, and at all treatment visits to confirm the subject 
has not become pregnant during the study, at a follow-up visit, and at the early-withdrawal
visit. 


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A negative pregnancy test 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).  Pregnancy tests may also be 
repeated if requested by institutional review boards (IRBs)/ethics committees (ECs) or if 
required by local regulations. 
Urine pregnancy tests must be sensitive to at least 25 mIU/mL and will be conducted with the 
test kit provided by the central laboratory in accordance with instructions provided in its 
package insert.  Subjects who have missed a menstrual period or who show an indeterminate
or positive result on the urine test may not further progress in the study until pregnancy is 
ruled out using further diagnostic testing (eg, a negative quantitative serum pregnancy test 
conducted at a certified laboratory).
In the case of a positive confirmed pregnancy, the subject will be withdrawn from
administration of investigational product but may remain in the study follow-up period. 
7.2.4. Purified Protein Derivative (PPD) Tuberculin Test
Subjects may be screened for TB using the PPD Tuberculin Test per local guidelines.  The 
test consists of an 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.
7.2.5. Interferon Gamma Release Assay Tuberculin Test
Subjects can be screened for tuberculosis using an IGRA per local guidelines.  IGRA will be 
tested locally 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.  Refer to local lab for any 
additional processing information and shipping instructions.  Testing may be performed by 
the central laboratory if necessary.


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7.2.6. Screening for Clostridium Difficile
C. difficile testing is performed at screening and during the study at Week 12 or early 
withdrawal visit.
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 local lab or central lab manual for further guidance and instruction for C. difficile
screening.
7.2.7. 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. 
Vital signs (including temperature) should be performed before laboratory blood collection 
and endoscopic procedure.
Sitting blood pressure will be measured with the subject’s arm supported at the level of the 
heart, and recorded to the nearest mmHg.  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 (C or F) be collected using tympanic, oral, or axillary 
methods and that the same method be used consistently throughout the study.
7.2.8. 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 
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(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).
7.2.9. 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.
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. 
7.2.10. 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.


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7.3. Diagnostic and Efficacy Assessments
7.3.1. Endoscopy
Video flexible sigmoidoscopy (with visualization to at a minimum, the splenic flexure 
segment) or colonoscopy should be performed within approximately 14 days of baseline, 
preferably 5 to 7 days prior to the baseline, to allow total Mayo score calculation.  Subjects 
with extensive UC of at least 8 years duration, with moderate or severe active inflammation 
(confirmed by endoscopy or histologically) who have not had a colonoscopy within 2 years 
prior to baseline will be excluded.  However, such subjects may be rescreened after a 
colonoscopy with biopsies as part of standard of care has been completed.  If visualization is 
not adequate for either colonoscopy or sigmoidoscopy due to suboptimal bowel prep, the 
procedure must be repeated.
The endoscopic subscore by the Central Reader must be available at the baseline visit.  The 
assessment by the Central Reader will be used to derive the total Mayo score for study 
eligibility.  The endoscopic report and pathology report must be available in the source 
documents. 
A video flexible sigmoidoscopy or colonoscopy (as preferred by the investigator) is also 
performed at the Week 12 visit or at the early withdrawal visit where applicable.  Bowel 
preparation should be conducted as per local routine.  The position of the endoscope at the 
Week 12 visit 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 endoscopy 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 endoscopy component should be completed at the end of the procedure to 
document the endoscopic subscore.
7.3.2. Biopsy Collection from Colonic Mucosa for Histology, RNA, Epigenetic, Tissue 
Concentration PF-06687234 and Tissue Protein
Colonic tissue biopsies will be collected at Screening, Week 12 and early withdrawal visit 
during the endoscopy.  Jumbo 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 endoscopy procedure, 9 biopsies (2 for histology, 1 for 
RNA, 3 for protein analysis and 3 biopsies for epigenetic and/or cytometry/microbiome
analysis) should be taken from abnormally inflamed colonic mucosa and 3 biopsies (for 
protein analysis including PF-06687234) should be taken from normal appearing colonic 
mucosa, resulting in a total of 12 biopsies from each subject, if possible.  All inflamed 
pre-treatment biopsies should be obtained in a targeted manner from the most affected are 
15-30 cm from the anal verge.  During post-treatment endoscopies, samples should be 
obtained from approximately the same anatomic location as the baseline assessment.  Frankly 
ulcerated areas should be avoided.  For all biopsies collected, record the colonic segment and 
approximate distance from the anal verge for each sample in the source documents.  If
12 biopsies cannot be collected during the endoscopy, then samples from inflamed tissues 
should be prioritized in the order of histology, RNA analysis, protein analysis/tissue 


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concentration PF-06687234, and epigenetic and/or cytometry/microbiome analysis.  During 
the baseline assessment, if increased inflammation is identified further than 15-30 cm, the 
location should be noted in the source documents (ie, colonic segment and approximate 
distance from anal verge) and additional 2 biopsies should be taken for histology both before 
and after treatment if possible.  If these 2 additional inflamed biopsies are taken for 
histology, then the total biopsies taken at pre and post endoscopy procedure will be 
14 biopsies (11 inflamed and 3 non inflamed biopsies). 
Histological, gene expression (RNA), protein analysis/tissue concentration PF-06687234 and 
epigenetic and/or cytometry/microbiome analysis may be conducted on the biopsy samples 
that are obtained.  Pfizer and the central laboratory vendor will provide sites with instructions 
for collection, processing, and shipment of biopsy samples.  These samples may be used for 
the evaluation of exploratory biomarkers that may include markers related to UC, Crohn’s 
disease and/or other inflammatory conditions and/or the mechanism of action of 
PF-06687234.  Detailed processing, storage and shipment instructions will be provided in the 
Lab Manual.
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 (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 (partial, modified or total see Appendix 2
and Appendix 3) will be calculated based on the subject’s stool diary recorded over 3 valid 
days closest to and prior to the visit date, where the invalid days are either the date of bowel 
preparation, date of endoscopy, any date between bowel preparation and endoscopy, or the 
date of endoscopy plus 1 day or 2 days prior to the endoscopy bowel preparation procedure.  
Investigator sites will be trained on the diary usage and will train subjects on use of the diary.  
Diary data entered by the subject will be reviewed by the site at each visit. 
If there are missing stool diary data, the average will be taken from the 3 most recently
available days reported within 5 days prior or 2 or more days after the endoscopy preparation 
for calculation of Mayo score. 


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If there only 2 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.
Note: If there is 1 day of diary data or no diary data recorded prior to the baseline (Day 1), 
then the subject cannot be randomized into the study.
Values used for Mayo score calculation should exclude any day when a bowel prep or 
endoscopy is performed.
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 
consider other observations (eg, physical findings) and subject’s performance status when 
making the PGA assessment.  In consequence, the PGA should be recorded after all other 
components of the Mayo score and relevant interval medical history and physical 
examination have been completed.  It is preferred that the same physician performs all such 
assessment for a given subject throughout the study.
The traditional total Mayo score at the screening visit must be 4 but no more than 9, with a 
traditional endoscopic subscore of 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 14 days. 
7.3.4. Subject Bowel Movement Diary
Subjects will use a diary in order to record on a daily basis the following information during 
the study:

‘Normal’ number of stools per day (eg, pre-UC diagnosis/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), ONLY if presence is noted.
In order to encourage consistent diary recording, subjects should enter diary data 
continuously throughout the study.  Instructions for completing the diary will be provided to 
subjects at screening and reviewed at subsequent visits.


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7.3.5. Partial Mayo Score
A partial Mayo Score (total Mayo Score excluding the endoscopic subscore, ranging from 
0 to 9 see Appendix 3) will be assessed at the times specified in the Schedule of Activities
section.  On dosing days, the partial Mayo Score should be assessed prior to administration 
of the IP.
7.3.6. Geboes Score
Colon biopsies obtained during screening and Week 12 endoscopies will be submitted for 
expert histology review.  A histological activity grading system referred to as “Geboes” 
which has demonstrated good reproducibility, will be utilized by a central reader and will be 
the basis for assessing histological changes pre and post treatment.29
7.3.7. Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
The UCEIS is a tool designed to measure disease activity for UC.  The UCEIS scoring 
system uses vascular pattern, bleeding and erosions/ulceration to provide an overall score of
endoscopic severity.
The UCEIS will be scored by the Central Reader.
7.4. Pharmacodynamics
The PD samples must be processed and shipped as indicated in the laboratory manual to 
maintain sample integrity.  Any deviations from the PD processing steps, 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.  
Depending on sampling and transport constraints, it is possible that not all biomarker samples 
will be collected in all study regions.
All efforts will be made to obtain the PD samples at the exact nominal time relative to 
dosing.  Please consult the laboratory manual(s) for final instructions on sample collection, 
storage, and shipping requirements.  These manual(s) supersede the instructions listed in the 
applicable protocol sections.  Samples that are handled according to the respective manual 
guidance are considered “per protocol”.
Samples will be analyzed using fit for purpose or validated analytical methods in compliance 
with Pfizer standard operating procedures.
As part of understanding the pharmacodynamics of the study drug and the disease under 
study, samples may be used for evaluation of the bioanalytical method.  These data will be 
used for internal (ie, Pfizer) exploratory purposes and will not be included in the clinical 
report.


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7.4.1. Exploratory Serum Protein Biomarkers
Blood samples (10 mL) for analysis of exploratory serum biomarkers will be collected into 
appropriately labeled glass tubes containing no preservatives; anticoagulant or serum 
separator according to the times specified in the Schedule of Activities and may be analyzed.  
Serum should be alliquotted before storing.
7.4.2. Exploratory Biomeasurement Immune Cells
Blood samples (2 ml) for epigenetic analysis and/or cytometry of immune cells will be 
collected into appropriately labelled tubes containing ethylenediaminetetraacetic acid 
(EDTA) according to the times specified in the Schedule of Activities and may be analyzed.
7.4.3. High-Sensitivity C-Reactive Protein (hsCRP)
Blood samples for determination of hsCRP will be obtained at the times specified in the 
Schedules of Activities and will be analyzed at the same laboratory performing the safety 
laboratory analyses.
7.4.4. Fecal Calprotectin
A stool sample for determination of fecal calprotectin will be obtained at the times specified 
in the Schedule of Activities.
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 as long as the sample is collected prior to the subject initiating 
the bowel preparation for endoscopy.
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.
7.4.5. Stool Samples for Exploratory Biomarkers (Microbiome)
A stool sample for microbiome analysis will be obtained at the times specified in the 
Schedule of Activities.  Sequencing of the DNA present in the stool will be performed.  DNA 
generally comes from microorganisms like bacteria, viruses, fungi and parasites that may be 
present in the stool.  During this process, some human DNA may be inadvertently sequenced, 
but will not be used for the final microbiome analysis.  The analysis vendors will analyze the 
DNA contained in the stool to better understand disease activity and response to therapy.
The study site personnel will provide appropriately labeled containers and instructions to the 
subject on how best to collect a sufficient stool 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 as long as the sample is taken prior to the subject initiating the 
bowel preparation for endoscopy.


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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-06687234 and Serum for Analysis of Infliximab
During the study blood samples (4 mL) to provide a minimum of approximately 1.5 mL
serum for pharmacokinetic analysis of PF-06687234 will be collected into appropriately 
labeled tubes containing K2 edetic acid EDTA at times specified in the SOA of the protocol. 
Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for
measurement of serum infliximab concentrations will be collected at time points specified in 
the Schedule of Activities.  PK sampling schedule may be modified based on emerging PK 
data. 
The actual sampling times for infliximab and PF-07787234 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.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures (SOPs).  The testing of the PK samples for infliximab will 
depend upon the sponsor’s decision and the results may not be reported in the clinical study 
report (CSR).
As part of understanding the PK of the study drug, samples may be used for metabolite 
identification and/or evaluation of the bioanalytical method, as well as for other internal 
exploratory purposes.  These data will be used for internal exploratory purposes and will not 
be included in the clinical report.  Samples collected for this purpose will be retained in 
accordance with local regulations and, if not used within this timeframe, will be destroyed.


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7.5.2. Additional PK Sampling
To characterize the PK of PF-06687234 a more extensive sampling scheme may be obtained 
in a subgroup of approximately 12 subjects who provide consent.  For these subjects 
undergoing the additional PK sampling, blood samples (4 mL) to provide a minimum of 
approximately 1.5 mL serum for pharmacokinetic analysis of PF-06687234 will be collected 
into appropriately labeled tubes containing K2 edetic acid EDTA at times specified in the 
SOA of the protocol.  The actual sampling times for these additional PK samples 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.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
SOPs.  As part of understanding the PK of the study drug, samples may be used for 
metabolite identification and/or evaluation of the bioanalytical method, as well as for other 
internal exploratory purposes.  These data will be used for internal exploratory purposes and 
will not be included in the clinical report.  Samples collected for this purpose will be retained 
in accordance with local regulations and, if not used within this timeframe, will be destroyed.
7.5.3. Shipment of Serum Samples for Analysis of PF-06687234 and Serum for Analysis 
of Infliximab
The shipment address and assay lab contact information for analysis of PF-06687234 
(including the additional PK samples) and infliximab will be provided to the investigator site 
prior to initiation of the study.
7.6. Immunogenicity
7.6.1. Plasma for Analysis of Human Anti-Fusion Antibodies (HAFA), Neutralizing 
Antibodies (NAb) Against PF-06687234 and Anti-Drug Antibodies Against Infliximab
To characterize immunogenicity against PF-06687234, blood samples (12 mL) to provide
approximately 8 mL plasma for HAFA and NAb analyses will be collected into appropriately 
labeled tubes containing K2 edetic acid [ethylenediaminetetraacetic acid] (EDTA) at times 
specified in the SOA of the protocol.


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For PF-06687234, a tiered immunogenicity testing strategy will be used: all samples that are 
positive will be confirmed for domain specificity.  The positive samples will be further 
characterized in the NAb assays, if bioanalytically feasible. 
Anti-drug antibody against infliximab may be tested and would require blood samples (6 ml) 
to provide minimum of 2 mL of serum to be collected into appropriately labeled tubes with 
no preservative (no anticoagulant and no serum separator gel may be used) at times specified 
in the SOA.  The testing of these immunogenicity samples for infliximab will depend upon 
the sponsor’s decision and the results may not be reported in the clinical study report (CSR).
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.  These data will be used for internal exploratory purposes and will not 
be included in the CSR.  Samples collected for this purpose will be retained in accordance to 
local regulations and if not used within this timeframe will be destroyed.
7.7. Pharmacogenomics 
7.7.1. Gene Expression Analysis
Blood samples for the assessment of gene expression (mRNA analysis) will be collected in 
appropriately labeled PAXgene Blood RNA Tubes.  Samples will be collected according to 
the times outlined in the Schedule of Activities.  These samples may be used for the 
evaluation of exploratory biomarkers that may include markers related to ulcerative colitis, 
Crohn’s disease and/or other inflammatory conditions and/or the mechanism of action of 
PF-06687234.  These samples are for biomarker analysis and will not be used for genetic 
testing.  Detailed processing, storage and shipment instructions will be provided in the Lab 
Manual.
Colon tissue biopsies will also be taken and may be used for histology, gene expression,
protein analysis and epigenetic and/or cytometry/microbiome and are described in 
Section 7.3.2.


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7.8. Banked Biospecimens
Banked biospecimens will be collected from subjects for exploratory research relating to the 
drug response and disease/condition under study.  These collections are not typically 
associated with a planned assessment described in the protocol.  They will be handled in a 
manner that protects each subject’s privacy and confidentiality.  Banked biospecimens will 
be assigned the subject’s study identification code (ID) at the site.  The data generated from 
these banked biospecimens will also be indexed by this ID.  Biospecimens will be kept until 
destruction in facilities with access limited to authorized personnel, and biospecimen-derived 
data will be stored on password-protected computer systems.  The key between the subject’s 
ID and the subject’s direct personally identifying information (eg, name, address) will be 
held at the study site.  Biospecimens will be used only for the purposes described in the 
protocol and informed consent document; any other uses require additional ethical approval.  
Unless a time limitation is required by local regulations or ethical requirements, 
biospecimens will be stored for many years (no time limit) to allow for research in the future, 
including research conducted during the lengthy drug-development process and also 
postmarketing research.  Subjects may withdraw their consent for the use of their banked 
biospecimens at any time by making a request to the investigator; in this case, any remaining 
biospecimens will be destroyed, but data already generated from the biospecimens will
continue to be available to protect the integrity of existing analyses. 
Unless prohibited by local regulations or ethics committee decision, a 4-mL blood genomic 
banked biospecimen Prep D1 (dipotassium edetic acid [ethylenediaminetetraacetic acid] 
[K2EDTA] whole-blood collection optimized for DNA analysis) will be collected at the 
time specified in the Schedule of Activities section of the protocol to be retained for potential 
pharmacogenomic/genomic/biomarker analyses related to drug response and 
disease/condition under study.  For example, putative safety biomarkers, drug-metabolizing 
enzyme genes, drug-transport protein genes, or genes thought to be related to the mechanism 
of drug action may be examined.  The primary purpose is to examine DNA; however, the 
biospecimen may also be used to study other molecules (eg, RNA, proteins, and metabolites).
Additional banked biospecimens to be retained for such exploratory analyses in this study 
include the following: 

Prep B1.5 (K2EDTA plasma collection optimized for 
biomarker/proteomic/metabonomic analysis): A 4-mL blood biospecimen will be 
collected at times specified in the Schedule of Activities section of the protocol.

Prep B2.5 (serum collection optimized for biomarker/proteomic/metabonomic 
analysis): a 4-mL blood biospecimen will be collected at times specified in the 
Schedule of Activities section of the protocol.

Prep R1 (PAXGene whole-blood collection optimized for RNA analysis): A 
2.5-mL blood biospecimen will be collected at times specified in the Schedule of 
Activities section of the protocol.


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The banked biospecimens will be collected from all subjects unless prohibited by local 
regulations or IRB/EC decision. 
It is possible that the use of these biospecimens may result in commercially viable products.  
Subjects will be advised in the informed consent document that they will not be compensated 
in this event.
7.8.1. Additional Research
Unless prohibited by local regulations or IRB/EC decision, subjects will be asked to indicate 
on the consent form whether they will allow banked biospecimens to also be used to design 
and conduct research in order to gain a further understanding of other diseases and to 
advance science, including development of other medicines for patients.
Subjects need not provide additional biospecimens for the uses described in this section; the 
biospecimens specified in the Banked Biospecimens section will be used.  Subjects may still 
participate in the study if they elect not to allow their banked biospecimens to be used for the 
additional purposes described in this section.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding,
occupational exposure 
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.


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Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious 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.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject.  In addition, each study subject will be questioned about the 
occurrence of AEs in a non-leading manner.


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8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 28 calendar days after the last administration of the investigational product.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
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.
8.1.5. 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 on the CRF, 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 investigational product caused or contributed to an AE; generally the facts 


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(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, 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, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. 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.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study 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 signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;


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
Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

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 (outside of any protocol-specified dose 
adjustments) 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 
recording as an AE.
8.2.3. 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.
Or that is considered to be:

An important medical event.


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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.
8.2.4. 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 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is 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 a 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 SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, 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.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
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In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  
In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;

For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The subject should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, GGT, PT/INR, total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 


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analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a co-formulated product in prescription or over-the-counter medications), 
recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected.  Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found.  Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability 
of all the results of the investigations performed to determine etiology of the LFT 
abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, regardless of 
whether an SAE has occurred.  In addition, the investigator must submit information 


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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) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the 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.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 


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accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors 
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an 
SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF.


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Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Sample Size Determination
The sample size calculation was based on the primary efficacy endpoint, proportion of 
subjects in clinical remission at Week 12.
It is anticipated that 22% of placebo subjects and 52% of subjects assigned to receive 
PF-06687234 will achieve a clinical remission rate at Week 12. The placebo rate of 
22% was selected based on published literature23 and internal meta-analysis of previous 
biological agents for ulcerative colitis. A sample size of 32 subjects in each treatment group 
(64 in total) is required to detect a treatment advantage of 30% in clinical remission with at 
least 80% power and a Type I error at 0.05 in a one-sided test.  Assuming a 15% dropout 
rate, the target sample size for recruitment is 38 per group.
Treatment failure approach will be used for missing value imputation from drop out subjects, 
ie, subjects who have missing value for any reasons will be considered as treatment failures.
If the recruitment rate is very slow, an interim analysis for futility will be done with 
approximately 20% and 40% randomized subjects for 12-week treatment.  Since the interim 
analysis is for futility only, type I error rate will not be affected.  
9.2. Efficacy Analysis
The primary analysis population will be based on a modified intent to treat (mITT) analysis 
set, which is defined as all randomized subjects who received at least one dose of randomized 
treatment.  A supportive analysis population will be based on a per-protocol (PP) population, 
which excludes those subjects who are identified as key protocol violators from mITT 
population.  Treatment failure approach will be used for missing value imputation from the 
subjects who drop out.
All endpoints will be evaluated at the 0.05 level of significance level (2-sided).
9.2.1. Analysis of the Primary Endpoint 
The primary objective is to establish the superiority of treatment to placebo for the primary 
efficacy endpoint of the proportion of subjects in clinical remission at Week 12.  The primary 
endpoint will be analyzed using exact Chan and Zhang method.22 The difference between 
treatment groups in the proportion of subjects in remission at Week 12 will be presented 
along with its 95% confidence interval.  Subjects with missing remission data at Week 12 


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will be treated as treatment failure.  As sensitivity analyses, the primary endpoint will also be 
analyzed using other methods for handling missing data which will be described in the SAP.
9.2.2. Analysis of Secondary Endpoints
The binary secondary endpoints, such as the proportion of subjects achieving endoscopic 
improvements or the proportion of subjects achieving clinical response, will be analyzed 
using the same approach as described for the primary endpoint.  Subjects with missing data at 
Week 12 will be treated as treatment failure. 
For continuous secondary endpoints that are only measured at baseline and Week 12, such as 
change from baseline at Week 12 in Geboes histology score will be analyzed using an 
analysis of covariance (ANCOVA) model with treatment group and baseline scores.  For 
binary/continuous secondary endpoints that are measured repeatedly over time, such as 
proportions of subjects with partial Mayo Score of 2 with no individual subscore >1, will be 
analyzed using generalized linear mixed effect model with treatment group, visit, treatment 
group by visit interaction and subjects as the random effect.  An unstructured covariance 
matrix will be assumed.
9.3. Analysis of Other Endpoints
All other continuous and binary data will be similar to the primary and secondary endpoints.  
The biomarker data, such as hsCRP data, fecal calprotectin data, the mean change from 
baseline and the corresponding confidence interval will be summarized by treatment group.  
Exploratory biomarkers will be summarized by dose group and may be graphically 
displayed; appropriate analysis may be performed as needed.  The analysis population will be 
based on a mITT analysis set and will not account for missing values.
9.3.1. Pharmacokinetic Analysis
The PK concentration population for PF-06687234 is defined as all enrolled subjects who 
received at least one dose of PF-06687234 and in whom at least one concentration value is 
reported.
PK concentrations will be summarized and presented with summary statistics. Data 
permitting exploratory non-compartmental analysis of the additional PK samples may be 
conducted and non-compartmental PK parameters AUC, Cmax, Tmax, t1/2, CL/F and Vz/F 
may be generated from these patients with additional PK sampling.  Details of the 
non-compartmental analysis method used for this exploratory analysis will be captured in the 
SAP.  Data permitting, concentration of PF-06687234 in the biopsy tissues will be 
summarized and presented with summary statistics.
A population PK model may be developed for the purpose of estimating population PK 
parameters.  Any population PK model developed to characterize the PK data will be 
reported separately.


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Data permitting, the relationship between exposure and clinical responses (efficacy and
safety) during 12 weeks of treatment in subjects with mild to moderate 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. 
Additionally, infliximab serum concentrations may be reported from all subjects enrolled in 
study.
9.3.2. Immunogenicity Analysis
The immunogenicity assessment population for PF-06687234 is defined as all enrolled 
subjects who received at least one dose of PF-06687234 with at least one post-treatment 
HAFA determination.
Overall incidence of development of HAFA 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 HAFA and NAb assays by time 
points samples would be collected.  Data permitting, the impact of HAFA and NAb on PK, 
PD, safety and efficacy profiles may be explored.
Additionally, ADA against infliximab may be reported from all subjects enrolled in study.
9.4. Safety Analysis
All clinical AEs, SAEs, treatment emergent adverse events (TEAEs), withdrawal due to AEs, 
ECGs, vital signs and safety laboratory data will be reviewed and summarized on an ongoing 
basis in a blinded manner during the study to evaluate the safety of subjects. 
The safety analysis will be based on a safety population, defined as all randomized subjects 
who received at least one dose of study treatment and all subjects will be analyzed according
to the treatment which they actually received.  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.  
Demographic data, medical history, physical examination, discontinuation and incidence of 
development of anti-drug antibodies and neutralizing antibody will be tabulated.  Safety lab 
parameters and vital signs will be summarized with absolute value and change from baseline. 
Subject listings will be produced for these safety endpoints accordingly. 
9.5. Interim Analysis 
Interim analysis for futility may be performed after approximately 20% (about 15 subjects)
and 40% (about 30 subjects) randomized subjects for 12-week treatment period, respectively.
Additional interim analysis may be conducted. If futility analysis criteria are reached, 
additional screening activities and enrollment/randomization will stop immediately.  
However, all subjects who are still participating in the active portions (treatment or follow-up
periods) of the study will continue to completion. 


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Interim analysis results may be used for internal business decisions regarding future study 
planning and stopping for futility.  Before any interim analysis is instigated, the details of the 
objectives, decision criteria, dissemination plan and method of maintaining the study blind as 
per Pfizer’s standard operating procedures (SOPs) will be documented and approved in an 
internal review committee (IRC) charter.  In addition, the analysis details will be documented 
and approved in an interim analysis SAP or final SAP.
9.6. Data Monitoring Committee (Internal Review Committee)
This study will use an internal review committee (IRC) which will be comprised of internal 
Pfizer experts, independent of the study team. 
The IRC will be responsible for ongoing monitoring of the efficacy and safety of subjects in 
the study according to the charter.  The IRC will review accumulating safety data and if 
needed propose changes to the protocol to ensure subject safety.  The recommendations made
by the IRC to alter the conduct of the study will be forwarded to the team for final decision. 
The team will forward such decisions, which may include summaries of aggregate analyses 
of endpoint events and of safety data that are not endpoints, to regulatory authorities, as 
appropriate. 
Additional information will be provided in the IRC charter.
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 investigator site may be subject to 
review by the IRB/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 investigator site for the inspection and will allow Pfizer or its
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.  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.


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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. 
In most cases, the source documents are the hospital or the physician subject chart.  In these
cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/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. 


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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 the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
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 numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator
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 and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.


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The informed consent documents used during the informed consent process and any subject 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC
before use, and available for inspection. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed, unless a waiver of 
informed consent has been granted by an IRB/EC. The investigator will retain the original of 
each subject's signed consent.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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 investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06687234 at any time.
If a study is prematurely terminated, 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 (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final 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 PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (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 the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, 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 it is 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 investigator sites, and that any subsequent publications 
by the PI 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.
Loftus EV et al., Clin Epi of IBD Gastroenterology 126(6):1504-1517(2004).
2.
Hanauer S.B., Present, D.H., and Rubin, D.T. Emerging Issues in Ulcerative colitis and 
Ulcerative Proctitis. Gastroenterol Hepatol (N Y). 2009 Jun; 5(6 Suppl 15): 4–16.
3.
Strik AS et al. Optimization of anti-TNF therapy in patients with Inflammatory Bowel 
Disease, Expert Review of Clinical Pharmacology, 2016 VOL. 9, NO. 3; 429-439.
4.
Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev 
Immunol. 2010 Mar;10(3):170-81.
5.
Schrieber S, Fedorak R, Nielsen O, et al. Safety and Efficacy of Human Recombinant 
InterLeukin-10 in Chronic Active Crohn’s Disease, Gastroenterology 2000; 
119:1461-1472.
6.
Taxonera C, Olivares D, Mendoza JL, Diaz-Rubio M, Rey E. Need for infliximab dose 
intensification in Crohn’s disease and ulcerative colitis. World J Gastroenterol. 2014; 
20(27):9170–7.
7.
Rostholder E, Ahmed A, Cheifetz AS, Moss AC. Outcomes after escalation of 
infliximab therapy in ambulatory patients with moderately active ulcerative colitis. 
Aliment Pharmacol Ther. 2012; 35(5):562–7.
8.
Yamada S, Yoshino T, Matsuura M, Minami N, Toyonaga T, Honzawa Y, et al. 
Long-term efficacy of infliximab for refractory ulcerative colitis: results from a single
center experience. BMC Gastroenterol. 2014; 14:80.
9.
Panaccione R, Ghosh S, Middleton S, Marquez JR, Scott BB, Flint L, et al. SUCCESS 
TRIAL - Combination therapy with infliximab and azathioprine is superior to 
monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014; 
146(2):392–400.
10.
Fedorak, R.N., et al., Recombinant human interleukin 10 in the treatment of patients 
with mild to moderately active Crohn’s disease. The Interleukin 10 Inflammatory 
Bowel Disease Cooperative Study Group. Gastroenterology, 2000. 119(6): p. 1473-82.
11.
Schreiber, S., et al., Safety and efficacy of recombinant human interleukin 10 in chronic 
active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. 
Gastroenterology, 2000. 119(6): p. 1461-72.
12.
Colombel, J.F., et al., Interleukin 10 (Tenovil) in the prevention of postoperative 
recurrence of Crohn's disease. Gut, 2001. 49(1): p. 42-6.
13.
Asadullah, K., W. Sterry, and H.D. Volk, Interleukin-10 therapy—review of a new 
approach. Pharmacol Rev. 2003, 55(2): p. 241-69.


PF-06687234
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14.
Tilg, H., et al., Treatment of Crohn’s disease with recombinant human interleukin 
10 induces the pro-inflammatory cytokine interferon gamma. Gut 2002. 50(2): p. 191-5.
15.
Doll F, Schwager K, Hemmerle T, & Neri D. Murine analogues of enanercept and of 
F8-IL10 inhibit the progression of collagen-induced arthritis in the mouse. Arthritis 
Research & Therapy, 2013; 15: R138.
16.
Samaan et al., An Update on Anti-TNF Agents in Ulcerative Colitis. Gastroenterol N 
Am. 2014; 43: p. 479-494.
17.
Kim Kwang-Nam, Watanabe S, Ma Y, Thorton S, Giannini EH and Hirsch R.  Viral 
IL-10 and Soluble TNF Receptor Act Synergistically to Inhibit Collagen Induced
Arthritis Following Adenovirus Mediated Gene Transfer. J Immunol 
2000;164:1576-1581.
18.
Nagy Z, Karadi O, Rumi G, Rumi Jr G, Par A, Mozsik , Czirjak Z, Suto G. Crohn’s 
disease is associated with polymorphism of CARD15/NOD2 gene in a Hungarian 
population. Annals of the New York Academy of Sciences, 2005; 1051:45-51.
19.
Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, 
Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer 
SB, Nunez G & Cho JH. A frameshift mutation in NOD2 associated with susceptibility 
to Crohn’s disease. Letters to Nature, 2001, 411: 603-606.
20.
Shouval DS, Ouahed J, Biswas A, Goettel JA, Horwitz BH, Klein C, Muise AM & 
Snapper SB. Interleukin 10 receptor signaling: master regulator of intestinal mucosal 
homeostasis in mice and humans. Advances in Immunology, 2014; Vol. 122, chapter 5.
21.
Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R and Bekker P. 
Combination therapy with etanercept and anakinra in the treatment of patients with 
rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis 
and Rheumatism; Vol 50:No5. May 2004. Pp 1412-1419.
22.
Chan ISF., Zhang Z. Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999; 55: 1201–1209.
23.
Jairath V, Zou G, Parker CE, et al. Systematic review with meta-analysis: placebo rates 
in induction and maintenance trials of ulcerative colitis. J Crohns and Colitis 2016; 
10(5): 607-618.
24.
Walmsley M, Katsikis PD, Abney E, Parry S, Williams RO, Maini RN, Feldmann M. 
Interleukin-10 inhibition of the progression of established collagen-induced arthritis. 
Arthritis Rheum 1996, 39: 495-503.
25.
Draft Guidance for Industry: Ulcerative Colitis Clinical Trials Endpoints. August 2016.


PF-06687234
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Page 126
26.
Guideline in the development of New Medicinal Products for the Treatment of 
Ulcerative Colitis: EMA Draft Guideline Rev. 1 (August 2016).
27.
Huhn et al. Pharmacodynamics and Immunomodulatory Properties of Intravenously 
Administered Recombinant Human Interleukin-10 in Healthy Volunteers. Blood 1996; 
87: 699-705.
28.
McInnees et al. IL-10 Improves Skin Disease and Modulates Endothelial Activation and
Leukocytes Effector Function in Patients with Psoriatic Arthritis.  The Journal of 
Immunology 2001; 167: 4075-4082.
29.
Geboes K.Gut 2000;47:404–409.
30.
Sampson HA, Munoz-Furlong A, Campbell RL, 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.
J Allergy Clin Immunol 2006;117(2):391-97.
31.
Gorski J et al. In vivo effects of interleukin-10 on human cytochrome P450 activity.  
Clinical Pharmacology & Therapeutics 2000; 67: 32-43.
32.
Taxonera C et al. Infliximab dose escalation as an effective strategy for managing 
secondary loss of response in ulcerative colitis. Digestive Diseases and Sciences 2015; 
60 (10): 3075-3084.
33.
Cesarini M et al. Dose optimization is effective in ulcerative colitis patients losing 
response to infliximab:A collaborative multicentre retrospective study. Dig Liver Dis.
2014; 46(2): 135-139.
34.
Yamada S et al. Long- term efficacy of infliximab for refractory ulcerative colitis: 
results from a single center experience. BMC Gastroenterology 2014;14 (80):1471-
1480.
35.
Fernández-Salazar L et al. Frequency, predictors and consequences of maintenance 
infliximab therapy intensification in ulcerative colitis. Rev Esp Enferm dig. 2015; 107 
(9): 527-533.
36.
Kornbluth A et al. Ulcerative Colitis Practice Guidelines in Adults: American College 
of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 
2010;105:501–523.


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Appendix 1. Abbreviations 
This following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
ADA
Anti-drug antibodies
AE
adverse event
ALT
alanine aminotransferase
ANC
Absolute neutrophil count
ANCOVA
Analysis of covariance
5-ASA
5-aminosalicylic acid
AST
aspartate aminotransferase
AUC
Area under the curve
AZA
azathioprine
BBS
Biospecimen Banking System
BCG
Bacillus Calmette-Guerin
-hCG
Beta-human chorionic gonadotropin
BP
Blood pressure
CD
Crohn’s disease
CK
creatine kinase
Cmax
Maximum observed concentration
CL/F
Apparent clearance
CMH
Cochran-Mantel Haenszel
CRF
case report form
CSA
clinical study agreement
CSF
cerebrospinal fluid
CSR
clinical study report
CT
Computerized tomography
CTA
clinical trial application
CTCAE
Common Terminology Criteria for Adverse Events
DILI
drug-induced liver injury
DLT
dose limiting toxicity
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
EDA
Extra-domain A
EDP
exposure during pregnancy
EDTA
ethylenediaminetetraacetic acid
eGFR
Estimated glomerular filtration rate
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration


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Abbreviation
Term
FMV
Fisrt morning void
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GDH
Glutamate dehydrogenase
GGT
Gamma-glutamyl transferase
GLP
Good Lab Practices
HAFA
Human Anti Fusion Antibody
HbA1c
Glycosylated hemoglobin
HBcAb
Hepatitis B core antibody
HBsAg
Hepatitis B surface antigen
HCVAb
Hepatitis C antibody
HCV
Hepatitis C virus
HEENT
Head eyes ears nose throat
HGB
hemoglobin
HIV
human immunodeficiency virus
hsCRP
high sensitivity C-reactive protein
IB
Investigator’s brochure
IBD
Inflammatory bowel disease
ICD
Immune complex deposition
ICD
Informed consent document
ICH
International Conference on Harmonisation
ID
identification
IGRA
interferon gamma release assay
IHC
immunohistology
IL-10
Interleukin-10
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISRs
Injection site reactions
IUD
intrauterine device
IUS
Intrauterine system
IV
intravenous
IWR
interactive web response
JAK
Janus kinase
JAK-STAT
Janus kinase signal transducers and activators of transcription
K2EDTA
dipotassium ethylenediaminetetraacetic acid
LFT
liver function test
LSLV
last subject last visit 
MAD
Mutual acceptance of data
MHC
Major histocompatibility complex


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Abbreviation
Term
mITT
Modified intent to treat
MTD
maximum tolerated dose
MTX
methotrexate
N/A
not applicable
Nabs
neutralizing antibodies
NK
Natural killer
NOAEL
no-observed adverse effect level
OECD
Organization for economic cooperation and development
PCD
primary completion date
PCR
polymerase chain reaction
PD
Pharmacodynamics(s)
PEF
Peak expiratory flow
PFS
prefilled syringe
PGA
Physicians global assessment
PGx
Pharmacogenomics(s)
PI
principal investigator
PK
pharmacokinetic
PP
Per protocol
PPD
purified protein derivative
PT
prothrombin time
PTT
Partial thromboplastin time
PV
Peripheral venous
QFT-G
QuantiFERON
QFT-GIT
QuantiFERON – Gold In-Tube
RA
Rheumatoid arthritis
RBC
red blood cells
RCTC
rheumatology common toxicity criteria
Rh
Recombinant human
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SADR
serious adverse drug reaction
SC
subcutaneous
scFv
fully human single chain variable fragment
SOA
Schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
sTNFR-Ig
soluble tumor necrosis factor receptor immunoglobulin
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TDM
Therapeutic drug monitoring
TEAE
Treatment emergent adverse event
T½
Terminal half-life


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Abbreviation
Term
TBili
total bilirubin
Tmax
Time to reach maximum concentration
TNF
Tumor necrosis factor
UA
urinalysis
UC
Ulcerative colitis
UCEIS
Ulcerative Colitis Endoscopic Index of Severity
ULN
upper limit of normal
US
United States
Vz/F
Apparent volume of distribution
WBC
White blood cells
WOCBP
Women of childbearing potential
WONCBP
Women of non-childbearing 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.
Reference: Schroeder KW, Tremaine WJ and Listrup DM. NEJM 1987;24;317(26) 1625-1629.


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Appendix 3. Glossary of Terms for Mayo Score Used in B7581002 Study
Traditional Total Mayo Score: 4 domains (Physicians global assessment, endoscopic, stool 
frequency, rectal bleeding)
Modified Total Mayo Score; 3 domains (Endoscopic, stool frequency, rectal bleeding)
Partial Mayo Score: 3 domains (Stool frequency, rectal bleeding and physicians global 
assessment
Traditional Endoscopic subscore - mild friability = 1, moderate or severe friability = 2
Modified Endoscopic subscore - ANY friability = 2


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Appendix 4. Clinical Criteria for Diagnosing Anaphylaxis Guidance30
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen 
lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING
a.
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia 
[collapse], syncope, incontinence)
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours):
c.
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, 
swollen lips-tongue-uvula)
d. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia)
e.
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence)
f.
Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)
3. Reduced BP after exposure to known allergen for that patient (minutes to several 
hours):
g. Infants and children: low systolic BP (age specific) or greater than 
30% decrease in systolic BP*
h. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from
that person’s baseline
PEF, Peak expiratory flow; BP, blood pressure.
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month 
to 1 year, less than (70 mm Hg + [2 X age]) from 1 to 10 years, and less than 90 mm Hg 
from 11 to 17 years. 


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Appendix 5. Protocol Specific Infliximab Biosimilars
The following infliximab biosimilar are approved for treatment in this protocol:
1. Inflectra
2. Remsima
The Sponsor may add other infliximab biosimilars to the list if needed.

SAP_001.pdf: 
Protocol B7581002 (PF-06687234) 
Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 1
Protocol B7581002
A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND 
PHARMACOKINETICS OF PF-06687234 AS ADD-ON THERAPY TO INFLIXIMAB 
IN ACTIVE ULCERATIVE COLITIS SUBJECTS WHO ARE NOT IN REMISSION 
(BUILD UC)
Statistical Analysis Plan 
(SAP)
Author: 
Version:
1.0
Date:
May 02, 2018
PPD


Protocol B7581002 (PF-06687234) 
Statistical Analysis Plan
PFIZER CONFIDENTIAL
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Objectives .......................................................................................................6
2.2. Study Design .............................................................................................................7
2.2.1. Study Overview ............................................................................................7
2.2.2. Additional Pharmacokinetic Sampling.........................................................7
2.3. Duration of Subject Participation..............................................................................8
2.4. Approximate Duration of Study................................................................................8
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ..................................................................................................................8
3.1. Primary Efficacy Endpoint........................................................................................8
3.2. Primary Safety Endpoint ...........................................................................................9
3.3. Secondary Endpoints.................................................................................................9
3.4. Exploratory Endpoints...............................................................................................9
3.5. Baseline Variables.....................................................................................................9
3.6. Safety Endpoints .....................................................................................................10
3.6.1. Adverse Events...........................................................................................10
3.6.2. Vitals and ECGs .........................................................................................10
3.6.3. Laboratory Data..........................................................................................11
4. ANALYSIS SETS ...............................................................................................................11
4.1. Full Analysis Set .....................................................................................................11
4.2. Per Protocol Analysis Set........................................................................................11
4.3. Safety Analysis Set..................................................................................................11
4.3.1. Pharmacokinetic (PK) Population ..............................................................11
4.3.2. Immunogenicity assessment population.....................................................11
4.4. Treatment Misallocations........................................................................................11
4.5. Protocol Deviations.................................................................................................12
4.5.1. Deviations Assessed Prior to Randomization.............................................12
4.5.2. Deviations Assessed Post-randomization...................................................12


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5. GENERAL METHODOLOGY AND CONVENTIONS....................................................12
5.1. Hypotheses and Decision Rules ..............................................................................13
5.2. General Methods .....................................................................................................13
5.2.1. Analyses for Binary Data............................................................................13
5.2.2. Analyses for Longitudinal Continuous Data ..............................................14
5.2.3. Analyses for Non-longitudinal Continuous Data .......................................14
5.2.4. Analyses for Categorical Data....................................................................14
5.2.5. Analyses for Time to Event Data................................................................14
5.3. Methods to Manage Missing Data ..........................................................................14
5.3.1. Binary Endpoint..........................................................................................15
5.3.2. Continuous Endpoints.................................................................................15
6. ANALYSES AND SUMMARIES ......................................................................................15
6.1. Primary Efficacy Endpoint: Clinical Remission .....................................................15
6.1.1. Primary Analysis ........................................................................................15
6.1.2. Sensitivity Analysis ....................................................................................15
6.1.3. Primary Safety Endpoint: ...........................................................................16
6.1.3.1. Primary Analysis.......................................................................16
6.2. Secondary Endpoint(s) ............................................................................................16
6.2.1. Binary Endpoint(s)......................................................................................16
6.2.2. Continous Endpoint(s)................................................................................17
6.3. Other Endpoint(s): Exploratory Endpoint(s)...........................................................17
6.3.1. Pharmacokinetic Analysis ..........................................................................18
6.3.2. Immunogenicity Analysis...........................................................................19
6.4. Subset Analyses.......................................................................................................19
6.5. Baseline and Other Summaries and Analyses.........................................................20
6.5.1. Baseline Summaries....................................................................................20
6.5.2. Study Conduct and Subject Disposition .....................................................20
6.5.3. Study Treatment Exposure .........................................................................20
6.5.4. Concomitant Medications and Non-Drug Treatments................................20
6.6. Safety Summaries and Analyses .............................................................................20
6.6.1. Laboratory Data..........................................................................................21
6.6.2. Vital Signs ..................................................................................................21
6.6.3. Electrocardiogram.......................................................................................21


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6.6.4. Physical Examination .................................................................................21
7. INTERIM ANALYSES.......................................................................................................22
7.1. Introduction .............................................................................................................22
7.2. Interim Analyses and Summaries............................................................................22
8. REFERENCES ....................................................................................................................23
9. APPENDICES .....................................................................................................................24
LIST OF TABLES
Table 1.
Summary of Major Changes in SAP Amendments................................................5
Table 2.
PK Parameters to be Summarized Descriptively..................................................18
LIST OF FIGURES
Figure 1.
Study Design Schematic.........................................................................................7
APPENDICES
Appendix 1. Summary of Efficacy Analyses...........................................................................24
Appendix 2. Definition and Use of Visit Windows in Reporting............................................25
Appendix 3. SAS Program Details ..........................................................................................26
Appendix 3.1. Estimate and Confidence Interval of a binomial proportion 
(Blyth-Still-Casella)..............................................................................................26
Appendix 3.2. Estimate and Confidence Interval for Risk Difference....................................26
Appendix 3.2.1. SAS code for the Confidence Interval for Risk Difference using Chan 
and Zhang (1999)..................................................................................................26
Appendix 3.2.2. SAS Code for GLIMMIX Analysis for Binary Data Analysis with 
Multiple Timepoints .............................................................................................26
Appendix 3.2.3. SAS Code for LMMs ....................................................................................26
Appendix 3.2.4. SAS Code for ANCOVA Models .................................................................27


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1. VERSION HISTORY
This Statistical Analysis Plan (SAP) for study B7581002 is based on the protocol dated 
06MAR2018.  
Table 1.
Summary of Major Changes in SAP Amendments
SAP Version
Change
Rationale
1
Not Applicable
Not Applicable
2. INTRODUCTION
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the 
gastrointestinal tract that affects five million people worldwide with considerable variability 
in incidence and prevalence by region.  The prevalence of IBD is highest in the second and 
third decade of life with another peak between 60 to 70 years of age.1  Ulcerative colitis 
(UC), one of two major phenotypes; the other is Crohn’s disease (CD), is characterized by 
continuous superficial mucosal inflammation that is localized to the colon and rectum.  UC 
involves a relapsing and remitting clinical course characterized by bloody diarrhea (with or 
without mucus), urgency, tenesmus, abdominal pain and weight loss, but can also present 
with variable extra intestinal manifestations in the eye, skin, and joint compartments.2  There 
is also an increased risk of colorectal cancer in UC patients compared to the general 
population.  Given the chronic nature of the condition, patients experience poor 
health-related quality of life, and the direct and indirect costs of clinical management 
represent a significant economic burden to society.
The goal of current treatments is to achieve resolution of signs and symptoms of active 
disease (clinical remission) in the short term and to decrease the frequency of subsequent 
disease flares in the long term.  In the setting of moderate to severe UC, the treatment 
algorithm includes 5-aminosalicylates, corticosteroids, immunomodulators (primarily 
azathioprine and 6-mercaptopurine), and monoclonal antibodies against tumor necrosis 
factor (TNF)-or 47 integrin.  Anti-TNF-therapies (infliximab, adalimumab, and 
golimumab) are the most commonly used biologic agents to treat UC.  However, some 
patients do not achieve clinical remission with anti-TNF-therapy, and up to 50% will 
develop loss of response over time.3 In these patients, a dose escalation strategy with
therapeutic drug monitoring (TDM) may be used to ensure adequate serum drug levels 
needed to achieve efficacy.  Another strategy is to explore the potential for additive benefit 
with the addition of another immunosuppressant as seen with the combination of infliximab 
with azathioprine in UC.15  However, such combinations targeting immune suppression are 
not without increased risk of serious infections and malignancies.  Consequently, safer and 
more efficacious approaches that combine other mechanisms of immune modulation are 
needed to improve therapeutic outcomes of existing therapies, offer additional options, and 
delay the need for surgical intervention, particularly in those with moderate to severe disease 
inadequately managed or refractory to standard treatments.


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Statistical Analysis Plan
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Page 6
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study B7581002.  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 Efficacy Objective

To evaluate the efficacy of PF-06687234 in induction of clinical remission in subjects 
with UC and a partial response to anti-TNF-.
Primary Safety Objective:

To evaluate the safety and tolerability of PF-06687234 in subjects with UC and a 
partial response to anti-TNF-.
Secondary Objectives

To evaluate the efficacy of PF-06687234 in induction of endoscopic improvement in 
subjects with UC and partial response to anti-TNF-.

To evaluate histological improvement in subjects with UC and partial response to 
anti-TNF-.

To evaluate the efficacy of PF-06687234 in induction of clinical response in subjects 
with UC and a partial response to anti-TNF-.

To describe the PK of PF-06687234 in subjects with UC.

To evaluate the immunogenicity of PF-06687234 in subjects with UC.
Exploratory Objective(s)

To collect banked biospecimens and additional non-banked samples (eg, intestinal 
biopsies, stool for microbiome analysis, serum and plasma for analysis of proteins, 
whole blood for RNA analysis and epigenetics and/or cytometry) for exploratory 
research, unless prohibited by local regulations or ethics committee decision.

To evaluate disease pathway and related biomarkers (ie, hsCRP and fecal 
calprotectin).

To describe the full PK profile in a subgroup of subjects.

To evaluate tissue concentrations of PF-06687234 in biopsy samples.


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2.2. Study Design
2.2.1. Study Overview
This is a Phase 2A, randomized, double-blind, placebo-controlled, parallel group, 
multicenter study in subjects with active UC and a non-remission (partial) response to 
anti-TNF-therapy.  Each subject will be randomly assigned to 1 of 2 treatment arms 
(1 active; 1 placebo) with approximately 98 subjects in total (49 subjects per arm) enrolled 
for the study to achieve a total of 78 evaluable subjects. 
Using the Mayo scoring definitions in Appendix 2 and Appendix 3 of the protocol, clinical 
remission is defined as those subjects with endoscopic subscore of 0 or 1, stool frequency 
subscore of 0 or 1 and rectal bleeding subscore of 0.
Eligible subjects for enrollment will meet criteria for non-remission during screening, 
despite at least 14 weeks of infliximab therapy for active UC. 
Women of childbearing potential (WOCBP) will be eligible for this study provided these 
women use two methods of contraception, as outlined in Section 4.4.1 of the protocol.
Figure 1.
Study Design Schematic
2.2.2. Additional Pharmacokinetic Sampling
For most subjects participating in Study B7581002 a sparse PK sampling scheme will be 
followed.  As the PK of PF-06687234 in UC subjects has not been characterized, to better 
understand the PK of PF-06687234, a more extensive PK sampling scheme may be used in a 
subgroup of approximately 12 subjects who provide consent from any investigational site.  
For specific details refer to Section 7.5.2 of the protocol regarding the additional PK 
sampling.


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2.3. Duration of Subject Participation
The duration of participation for eligible subjects will be approximately 26 weeks.  This will 
include a 4-week screening period, a 12-week treatment period, a 10-week follow-up period 
which will include a telephone contact conducted 6-weeks after the onsite follow-up visit.  
During the treatment period subjects will visit the clinic every week (2 days) for SC 
administration of 20 mg of the investigator product (IP) or placebo for a total of 12 visits.  In 
addition, all subjects enrolled in the study will be provided with their infliximab therapy 
(5-10 mg/kg) during the 12-week treatment period and at Week 16 visit.  Subjects will be 
administered their infliximab therapy by IV administration at the clinic on Day 1, Week 8 
visit (2 days) and at the final onsite visit at Week 16.
Subjects will be required to return to the clinic for one visit 4 weeks after the last visit during 
the treatment period to evaluate for safety which will constitute the in person follow-up 
period.  Subjects will also be administered their infliximab therapy at this visit.  There will be 
a telephone contact conducted 6 weeks after this visit to confirm any SAEs have been 
reported to Pfizer post the final infliximab infusion at Week 16 and to provide results of 
Week 16 immunogenicity testing.
Subjects with no detectable HAFA(Human Anti-Fusion Antibodies) or Nab (Neutralizing 
Antibodies) against IL-10 portion of PF-06687234 by the Week 16 visit will require no 
further follow-up beyond the Week 22 telephone contact.  However, subjects with detectable 
HAFA or NAb against the IL-10 portion of PF-06687234 at Week 16 will be informed of 
their immunogenicity status at the Week 22 telephone contact.  These subjects will be 
required to return for an onsite visit at Week 28 for repeat immunogenicity testing.  If these 
subjects have detectable HAFA or NAb against the IL-10 portion of PF-06687234 from the 
immunogenicity sample collection at Week 28, they will require one additional follow-up 
collection 3 months after Week 28 at approximately Week 40.
2.4. Approximate Duration of Study
Study enrollment is estimated to be completed in approximately 19 months.  The completion 
of the study is estimated to occur in approximately 26 months.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Efficacy Endpoint
Proportion of subjects in clinical remission at Week 12 (as defined by a modified Mayo Score 
with an endoscopic subscore 1, stool frequency subscore 1 and rectal bleeding
subscore = 0).a,b
a.
The assessment of clinical remission will utilize the current definition of the Mayo endoscopic subscore, which allows 
for assessment of mild friability in the subscore of 1. 
b.
The Central Readers for endoscopy Mayo subscores will also employ an assessment as to the presence or absence of 
any friability (including mild).  In this assessment the presence of any friability (including mild) will be scored as 2.  


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3.2. Primary Safety Endpoint

Incidence and severity of adverse events, serious adverse events and withdrawals due 
to adverse events, ECGs, vital signs and safety laboratory tests.
3.3. Secondary Endpoints

Proportion of subjects with endoscopic improvement at Week 12 (defined as decrease 
of 1 point in Mayo endoscopy score or an absolute endoscopy score of 1.)b

Mean change from baseline at Week 12 in Geboes histology score. 

Proportion of subjects with a clinical response at Week 12 defined with a decrease 
from baseline of at least 3 points in total Mayo score with at least 30% change, 
accompanied by at least one point decrease or absolute score of 0 or 1 in rectal 
bleeding subscore.

Proportion of subjects with change from baseline in partial Mayo Score of 2 with no 
individual subscore >1 at Weeks 2, 4, 6, 8, 12.

Plasma concentrations of PF 06687234. 

Incidence of the development of HAFAs and Nabs against PF 06687234.
3.4. Exploratory Endpoints

Collection of banked biospecimens and additional non banked samples (eg, intestinal 
biopsies, stool for microbiome analysis, serum and plasma for analysis of proteins, 
whole blood for RNA analysis and epigenetics and/or cytometry) unless prohibited by 
local regulations or ethics committee decision.  Additional information on collection 
and potential use is provided in the Banked Biospecimens section.

Change from baseline in fecal calprotectin at Weeks 4, 8, 11.

Change from baseline in hsCRP at Weeks 4,8,11.

AUCτCmax, Tmax, t1/2, CL/F, Vz/F as data permit.

PF 06687234 tissue concentration in inflamed and non inflamed biopsies.
3.5. Baseline Variables
The covariates added into the analyses will be the baseline score (eg, in Longitudinal data 
analysis).


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Covariates will be summarized for the mITT (FAS) and PP population, split by treatment 
group. Continuous baseline covariates will be summarized by: n, mean, median, standard 
deviation, min and max. Binary and factor covariates will be summarized by percents and 
counts.
3.6. Safety Endpoints
3.6.1. Adverse Events

Safety and tolerability of PF-06687234 dose levels versus placebo: Adverse Events 
(AE), Serious Adverse Events (SAE), treatment-emergent adverse events (TEAE), 
withdrawal due to adverse events. Any adverse events that start or increase in 
severity following the start of treatment and occur within the follow-up period after 
the end of treatment will be considered as TEAE.

Potential cases of drug-induced liver injury (ALT and AST elevation).

Laboratory tests as specified in the protocol.

Vital signs (blood pressure, heart rate, respirations and oral or tympanic temperature) 
will be measured at every study visit.

ECG, single 12-lead ECGs will be obtained on all subjects at specified visits.

Other safety endpoints including hospitalization, physical examination, weight, and 
concomitant medications,  data will be collected.
A 3-tier approach will be used to summarize clinical AEs. Under this approach, AEs are 
classified into 1 of 3 tiers. Different analyses will be performed for different tiers (See 
Section 8.2.3 of the protocol). 
Tier-1 events: no Tier-1 AE has been identified/specified.
Tier-2 events: A MedDRA PT is defined as a tier-2 event if it has at least 4 frequencies in 
any treatment group.
Tier-3 events: All other events are defined as tier-3 events.
3.6.2. Vitals and ECGs
Baseline for vitals and ECG will be defined as the last pre-dose value before the first dosing.
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula: QTcF 
= QT / (RR)^(1/3), where RR = 60/HR (if RR is not provided).
note: if QTcB is collected, then it should be listed only.


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3.6.3. Laboratory Data
Using the current Pfizer data standards, the last pre-dose value before the first dosing is used 
as the baseline for all laboratory parameters. 
4. ANALYSIS SETS
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in 
each analysis population prior to unblinding and releasing the database and classifications 
will be documented per standard operating procedures.
4.1. Full Analysis Set
The Full Analysis Set is defined as all subjects randomized and who have received at least 
one dose of randomized treatment, which will also be called modified ITT (mITT) 
population. All efficacy, PD, and biomarker analyses will be primarily performed with the 
mITT population.
4.2. Per Protocol Analysis Set 
The Per Protocol (PP) population will be a subset of the mITT population, which excludes 
those subjects who are identified as key protocol violators from mITT population.  
4.3. Safety Analysis Set
The safety population includes all enrolled subjects who received at least 1 dose of
investigational product. Subjects who are enrolled and treated but not randomized for 
various reasons will also be included in the safety population. All patients will be analyzed 
according to the treatment which they actually received. All safety analyses will be primarily
based on the safety population. 
4.3.1. Pharmacokinetic (PK) Population
The PK population is defined as all subjects who received at least 1 dose of investigational
product and have data on at least one PK concentration. The PK population will be used for 
concentration-time data listings for the clinical study report.
4.3.2. Immunogenicity assessment population
The immunogenicity assessment population for PF-06687234 is defined as all enrolled 
subjects who received at least one dose of PF-06687234 with at least one post-treatment 
HAFA determination. 
4.4. Treatment Misallocations 
If a subject was: 

Randomized but not treated, the subject will appear on the subject disposition table 
and listing as randomized but not treated; They will be excluded from all (efficacy, 
safety, PK, PD, biomarker, health outcome and immunogenicity) analyses as they 
have not received at least one dose of study medication.


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
Treated but not randomized, then they will be excluded from the efficacy analyses 
(both mITT and PP) since randomized treatment is missing, but will be reported 
under the treatment they actually received for safety analyses. They may also be 
included in the exploratory biomarker analyses.

Randomized but took incorrect treatment: if a subject received the incorrect treatment 
for the whole duration of the Week 0-12 period then they will be reported under the
randomized treatment group for all efficacy analyses (including baseline tables), but 
will be reported under the treatment they actually received for all safety analyses; if a 
subject received the incorrect treatment at only some dosing occasions then the 
subject will be reported under their randomized treatment group for all efficacy and 
safety analyses, but the subject will be excluded from the per-protocol population and 
may be excluded form the exploratory biomarker analyses if sufficient doses were 
incorrect and therefore deemed as a major protocol deviation.
4.5. Protocol Deviations
Different protocol deviation may have a different impact on the analyses. A full list of 
protocol deviations will be compiled and reviewed by the Clinician and the statistician to 
identify major and minor deviations prior to database release. Those major protocol 
deviations will be noted by declaring the subject to be a key protocol violator. Per the SAP, a 
key protocol violator will be excluded from the per-protocol analysis set.
4.5.1. Deviations Assessed Prior to Randomization
During the screening phase (prior to randomization), the investigator will assess and 
document subject eligibility against the inclusion and exclusion criteria as set out in sections 
4.1 and 4.2 of the protocol.  Any subject that does not meet the inclusion and exclusion 
criteria should not be randomized.
4.5.2. Deviations Assessed Post-randomization
Any significant deviation from the protocol occurring after randomzation will be reviewed 
prior to database release and a decision will be made regarding whether a subject is identified 
as a key protocol violator who should be excluded from the per-protocol analysis set.
5. GENERAL METHODOLOGY AND CONVENTIONS
Final analyses will occur after database lock after Last Subject Last Visit (LSLV).
An interim analysis for futility may be performed with 40% completers.
All subjects, investigators, and site personnel will continue to be blinded to randomized study 
treatments throughout the  period of the study. The database will be officially released after 
last subject last visit occurs. The final analysis will be then conducted and the CSR will be 
issued. The decision rules for the final analyses are also described in the next section.


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5.1. Hypotheses and Decision Rules
Active treatmentwill be considered superior to placebo with respect to response in primary 
efficacy endpoint, proportion of subjects in clinical remission at Week 12, if the difference is 
statistically significant at the two-sided 0.05 level.
Sample Size
The sample size calculation was based on the primary efficacy endpoint, proportion of 
subjects in clinical remission at Week 12.
It is anticipated that 22% of placebo subjects and 52% of subjects assigned to receive 
PF-06687234 will achieve a clinical remission rate at Week 12.  A sample size of 39 subjects 
in each treatment group (78 total) is required to detect a treatment advantage of 30% in 
clinical remission with at least 80% power and a Type I error at 0.05 in a two-sided test.  
Assuming a 20% dropout rate, the target sample size for recruitment is 49 per group.
No investigational study has to date been completed in a UC population receiving infliximab 
therapy with mild to moderate levels of residual active disease. Based on available literature 
(Jairath et al, 2016),3 and internal meta-analyses of updated clinical data available in the 
current literature, the placebo response rate of clinical remission in moderate to severe UC 
patients is assumed to be 0% to 15%. In mild to moderate disease, it is expected that the 
placebo response rate would be even higher. After careful consideration of the overall 
context of use and in consultation with external key inflammatory bowel disease (IBD)
disease experts, a placebo rate of 22% and treatment rate of 52% are assumed for this design, 
which will guide continued clinical development for UC.
Treatment failure approach will be used for missing value imputation from drop out subjects, 
ie, subjects who have missing value for any reasons will be considered as treatment failures.
If the recruitment rate is very slow, an interim analysis for futility will be done with 
40% completers.  Since the interim analysis is for futility only, type I error rate will not be 
affected.  A conditional power less than 10% will be used for futility.
5.2. General Methods 
In general, number and percent will be presented for binary and categorical variables.  
Number, mean, standard deviation (or standard error of the mean), median, minimum, and 
maximum will be presented for continuous variables.  In addition, graphics may be used to 
present the data – specific details will be outlined in the study List of Table (LOT).
5.2.1. Analyses for Binary Data
All binary data comparing active treatment group and placebo group will be analyzed using 
the unconditional exact Chan and Zhang (1999) method.1  Rate (%) differences and the 
corresponding 2-sided 95% confidence intervals will be computed using this methods. 
Confidence interval of a single proportion will be computed using Blyth-Still-Casella 
method.


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For binary endpoints that are measured repeatedly over time, will be analyzed using 
generalized linear mixed effect model with treatment group, visit, treatment group by visit 
interaction and subjects as the random effect.  An unstructured covariance matrix will be 
used to fit such model. In case, if the model fails to converge, a covariance structure such as 
compound symmetry or autoregressive model may be used. Bayesian information criterion 
(BIC) will be used to assess the goodness of fit of the models. The model with the smallest 
BIC will be selected for inference. P-values and inference for relative risks between 
treatments will be provided based on the link function of logit. The SAS code to be used to 
compute the confidence intervals of relative risks, and difference of relative risks adjusting 
any covariates is given in the appendix.
5.2.2. Analyses for Longitudinal Continuous Data
Descriptive statistics (n, mean, median, standard deviation, minimum and maximum) for 
continuous endpoints will be summarized and presented by dose cohort (and by each planned 
measurement time point if applicable). Geometric Mean may be provided as necessary.
Mixed Effect Model Repeat Measurement (MMRM): The fixed effects of treatment, visit, 
and treatment-by-visit interaction will be included, along with patient as a random effect.  
Unstructured covariance matrix will be assumed.  The baseline infliximab concentration and 
ADA status as covariate  may be added to the model as a part of sensitivity analsysis.
When modeling the change from baseline values, the variable of visit will start with the first 
post-baseline visit, and the actual baseline value will be included as a covariate.  At each 
visit, estimates of mean values and the mean differences between the active treated group and 
the placebo group will be derived from the model.  The corresponding p-values, standard 
errors and 95% confidence intervals will also be derived from the model.
5.2.3. Analyses for Non-longitudinal Continuous Data
Analysis of Covariance (ANCOVA): The non-longitudinal continuous data will be analyzed 
by ANCOVA with treatment as the factor.  When modelling change from baseline values, the 
actual baseline value will be included as a covariate.  Active dose group will be contrasted 
versus placebo.
5.2.4. Analyses for Categorical Data
None.
5.2.5. Analyses for Time to Event Data
None.
5.3. Methods to Manage Missing Data
Observed data will be used for descriptive statistics, ie, missing data will not be imputed.  
Unless there is an explicit instruction, missing values will be used for lower limits of 
detection and quantitation.


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No explicit missing value imputation will be used for longtitudinal models (such as Linear 
Mixed model or Generalized Linear Mixed Model) as under the missing at random (MAR) or 
missing completely at random (MCAR) assumptions missing values are already incorporated 
into those models.  
No missing values will be imputed for analyses of exploratory biomarkers.
5.3.1. Binary Endpoint
For the binary response endpoints, subjects with missing values will be handled by treatment 
failure approach (TFA) ie, setting any missing values to be non-responsive (0).
5.3.2. Continuous Endpoints
For non-patient reported outcome variables, the missing continuous data will be used as is 
(Observed Case – OC). The Baseline Observation Carried Forward (BOCF) approach may 
be used to handle the monotone missing data or no post baseline measurements. Using 
BOCF, the baseline values will be carried forward for the visits after which subjects 
prematurely discontinued assigned treatment.
6. ANALYSES AND SUMMARIES
6.1. Primary Efficacy Endpoint: Clinical Remission
6.1.1. Primary Analysis

Endpoint: Proportions of subjects achieving clinical remission at Week 12.

Analysis population: FAS.

Analysis methodology: Exact Chan and Zhang method.  

Missing Data: Missing data will be handled by TFA.
6.1.2. Sensitivity Analysis

Endpoint: Proportions of subjects achieving clinical remission at Week 12.

Analysis population: Observed Cases (OC) and Per-Protocol (PP).

Analysis methodology: Confidence interval of a proportion will be computed using 
Blyth-Still-Casella method, and the difference in proportions will be computed using 
Exact Chan and Zhang method.  

Missing Data: Missing data will be handled by TFA
Reporting results:

Raw data: The sample size, percentage, and corresponding 95% confidence intervals 
for each treatment arm, difference of proportions, corresponding confidence intervals 
and 2-sided pvalue  will be presented.


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Figures

Vertical barchart of proportions and coresponding 95% confidence interval of clinical 
remission patients at Week 12 for treatment and placebo arms.
6.1.3. Primary Safety Endpoint: 
6.1.3.1. Primary Analysis

Endpoint: Incidence and severity of adverse events, serious adverse events and 
withdrawals due to adverse events, ECGs, vital signs and safety laboratory tests.

Analysis population: Safety Analysis Set.

Analysis methodology: Will be analyzed in accordance with Pfizer Data Standards.  

Missing Data: Observed Cases (OC).
Reporting results:

All safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, categorical summaries, and graphical presentations.
6.2. Secondary Endpoint(s)
For all Secondary Endpoints will be analyzed based on FAS.
6.2.1. Binary Endpoint(s)
Following binary secondary endpoints will be analyzed similar to the primary efficacy 
endpoint:

Proportion of subjects with endoscopic improvement at Week 12 (defined as decrease 
of 1 point in Mayo endoscopy score or an absolute endoscopy score of 1).b

Proportion of subjects with a clinical response at Week 12 defined with a decrease 
from baseline of at least 3 points in total Mayo score with at least 30% change, 
accompanied by at least one point decrease or absolute score of 0 or 1 in rectal 
bleeding subscore.

Proportion of subjects with change from baseline in partial Mayo Score of 2 with no 
individual subscore >1 at Weeks 2, 4, 6, 8, 12.

Incidence of the development of HAFAs and Nabs against PF-06687234.
For binary secondary endpoints that are measured repeatedly over time will be analyzed 
using generalized linear mixed model (specified in Section 5.2.1). 


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6.2.2. Continous Endpoint(s)
The following secondary endpoints will be analyzed per the following:

Mean change from baseline at Week 12 in Geboes histology score. 

Analysis time points: Week 12.

Analysis population (method of imputation for missing data): FAS (BOCF)
Analysis methodology: Change from baseline will be analyzed using the ANCOVA 
model (specified in Section 5.2.3). 

Plasma concentrations of PF-06687234. 

Analysis time points: Week 12.

Analysis population (method of imputation for missing data):  PK
Analysis methodology: Change from baseline will be analyzed using the MMRM
method (see Section 5.2.2) with no imputations for any missing data (OC), ie,
subjects with partial data will be included in MMRM analysis.
Reporting results:

Raw data: The sample size, mean, standard deviation, median, minimum and 
maximum at baseline and post-baseline visits will be presented for each treatment 
arm.

Change from baseline: The sample size, mean, standard deviation, median, minimum 
and maximum will be presented for each treatment arm. The LS means, 
95% confidence interval for the LS means, difference between the LS means for each 
pair of treatment groups and the corresponding 95% confidence interval will be 
presented.  
Figures
Vertical bar chart of placebo adjusted LS means and 95% confidence interval at 
Week 12.
6.3. Other Endpoint(s): Exploratory Endpoint(s)

Collection of banked biospecimens and additional non-banked samples (eg, intestinal 
biopsies, stool for microbiome analysis, serum and plasma for analysis of proteins, 
whole blood for RNA analysis and epigenetics and/or cytometry) unless prohibited by 
local regulations or ethics committee decision.  Additional information on collection 
and potential use is provided in the Banked Biospecimens section and in the 
exploratory analysis plan (EAP).

Change from baseline in fecal calprotectin at Weeks 4, 8, 11.


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
Change from baseline in hsCRP at Weeks 4,8,11.

AUCτCmax, Tmax, t1/2, CL/F,and Vz/F as data permit.

PF-06687234 tissue concentration in inflamed and non-inflamed biopsies.
All other continuous and binary data will be similar to the primary and secondary endpoints.  
The biomarker data, such as hsCRP data, fecal calprotectin data, the mean change from 
baseline and the corresponding confidence interval will be summarized by treatment group.  
Exploratory biomarkers will be summarized by dose group and may be graphically 
displayed; appropriate analysis may be performed as needed.  The analysis population will 
be based on a mITT analysis set and will not account for missing values. Some of the 
exploratory endpoint analyses such as analyses related to fecal calprotectin and hsCRP 
endpoints may be included in the CSR.
6.3.1. Pharmacokinetic Analysis
Actual PK sampling times will be used in the derivation of PK parameters. 
If a PK parameter cannot be derived from a 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 summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular dose with 3 evaluable measurements.  If an individual 
subject has a known biased estimate of a PK parameter (due for example to an unexpected 
event), this will be footnoted in summary tables and will not be included in the calculation of 
summary statistics or statistical analyses.
The following PK parameters will be calculated for PF-06687234 (as data permits) from the 
concentration-time values using standard noncompartmental methods from patients with 
additional PK sampling: AUC, Cmax, Tmax, t1/2, CL/F and Vz/F.
To assess the pharmacokinetics of PF-06687234, PK parameters will be listed and 
summarized for subjects in the PK analysis set and will include the set of summary statistics 
as specified in the table below:
Table 2.
PK Parameters to be Summarized Descriptively
Parameter
Summary Statistics
AUCτ, Cmax, CL/F and 
VZ/F
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum, geometric mean and geometric cv%.
Tmax
N, median, minimum, maximum.
t1/2
N, arithmetic mean, median, cv%, standard deviation, 
minimum, maximum.


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There will be 1 summary table presenting all PK parameters.  This will include data from all 
treatments.  The treatment subheading will include the dose information and any other 
pertinent information related to the intense PK population .  
Median trough concentration plots will be generated for all subjects. For subjects with 
additional PK samples, median concentration time plots (linear and log scale) on Visit 1 and 
Visit 12 will be generated. 
Data permitting, concentration of PF-06687234 in the biopsy tissues will be summarized and 
presented with summary statistics.
A population PK model may be developed for the purpose of estimating population 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 mild to moderate UC may be explored 
using either observed or modeled exposures.
Additionally, infliximab serum concentrations by treatment group may be summarized and 
presented.
6.3.2. Immunogenicity Analysis
Overall incidence of development of HAFA 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 HAFA and NAb assays by time 
points samples would be collected.  Data permitting, the impact of HAFA and NAb on PK, 
PD, safety and efficacy profiles may be explored. Data permitting, median concentration 
time profile in HAFA/NAb positive subjects will be compared with that in HAFA/NAb ngative 
subjects.
Additionally, ADA against infliximab may be summarized and reported if data permits.
6.4. Subset Analyses 
Proportion of subjects achieving clinical remission at Week 12 may be summarized for the 
subsets below (tables will be generated if we have sufficient number of subjects in each 
stratum):

Anti-TNF experience (yes or no);

Steroid use at baseline (yes or no);

Gender: Female/Male;

Disease duration;

Fecal Calprotectin at baseline: <=500, >500 ug/g and <=250, >250 ug/g.


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6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Demographics and medical history including variables defined in Section 3.3 will be 
summarized by treatment group according to Pfizer standards.
6.5.2. Study Conduct and Subject Disposition
Subjects evaluation, disposition, discontinuation will be summarized according to Pfizer 
standards.
6.5.3. Study Treatment Exposure
A summary of compliance and the number of doses received as well as the median total dose 
by visit and treatment group will be provided.
The exposure to study drug will be summarized by total number of applications, the total 
number of days of dosing, and number and percentage of subjects who are compliant with the 
dosing regimen.
6.5.4. Concomitant Medications and Non-Drug Treatments
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to Pfizer standards.
6.6. Safety Summaries and Analyses
Safety analysis will be based on the SAF analysis set.
Safety and tolerability of PF-06687234 dose levels versus placebo: Adverse Events (AE), 
Serious Adverse Events (SAE), treatment-emergent adverse events (TEAE), withdrawal due 
to adverse events.  All clinical AEs, SAEs, treatment-emergent signs and symptoms
(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. Any adverse events that start or increase in severity following the start of treatment 
and occur within the follow-up period after the end of treatment will be considered as TEAE.

Potential cases of drug-induced liver injury (ALT and AST elevation).

Laboratory tests as specified in the protocol.

Vital signs (blood pressure, heart rate, respiration and oral or tympanic temperature) 
will be measured at every study visit.

ECG, single 12-lead ECGs will be obtained on all subjects at specified visits.
Other safety endpoints including hospitalization, physical examination, weight, concomitant 
medications.


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A 3-tier approach will be used to summarize clinical AEs.  Under this approach, AEs are 
classified into 1 of 3 tiers.  However, no Tier-1 AE has been identified for this study. 
Different analyses will be performed for different tiers (See Section 8.2.3 of the protocol). 
The MedDRA preferred term, treatment in B7581002 study, n (%) for eachMedDRA 
preferred term per arm, risk difference, 95% confidence interval and p-values for the risk 
difference will be provided.  Graphical format may be presented aswell. Presented in 
descending p-value order. Please note that this analysis is exploratory in nature.
The -pvalues will be presented for descriptive purpose only and no definitive conclusion 
should be made based on the p-values. Tier-2 events: A MedDRA PT is defined as a 
tier-2 event if it occurs in at least 4 subjects in any treatment group.
Tier-3 events: All other events are defined as tier-3 events.
It should be recognized that most studies are not designed to reliably demonstrate a causal 
relationship between the use of a pharmaceutical product and an adverse event or a group of 
adverse events. Except for select events in unique situations, studies do not employ formal 
adjudication procedures for the purpose of event classification. As such, safety analysis is 
generally considered as an exploratory analysis and its purpose is to generate hypotheses for 
further investigation. The 3-tier approach facilitates this exploratory analysis.
6.6.1. Laboratory Data
Using the current Pfizer data standards, the last pre-dose value before the first dosing is used 
as the baseline for all laboratory parameters. 
6.6.2. Vital Signs
Baseline for vitals and ECG will be defined as the last pre-dose value before the first dosing.
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula: QTcF 
= QT / (RR)^(1/3), where RR = 60/HR (if RR is not provided).
note: if QTcB is collected, then it should be listed only.
6.6.3. Electrocardiogram
ECG parameters, if applicable, will be summarized at:

Baseline, Week 12, and Early Termination of induction period
6.6.4. Physical Examination
Physical examinations will be summarized at:

Baseline, Week 12, and Early Termination of induction period.


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7. INTERIM ANALYSES
7.1. Introduction
If the recruitment rate is very slow, an interim analysis for futility will be done with 
40% completers.  Since the interim analysis is for futility only, type I error rate will not be 
affected.  A conditional power less than 10% will be used for futility. An Internal Review 
Committee (IRC) is established to oversee this Pfizer-sponsored trial.  The primary rationale 
for establishing the committee is to make certain that appropriate safeguards are in place to 
help ensure the safety of subjects and/or to maintain scientific rigor and study integrity for 
these studies with planned interim analyses where treatment arms may be compared or a 
single treatment arm may be assessed with respect to the accumulating safety while the trial 
is on-going.  The IRC is an independent oversight committee comprising 3 qualified and 
experienced Sponsor experts in their respective fields, but who are external to and 
independent of the study and the study team. The IRC consists of a chairperson and at least 
2 additional members, including at least one with medical qualifications and at least one 
other who is a statistician. All members of the IRC will be unblinded voting members, and 
must be qualified and experienced in reviewing and interpreting clinical study data.  A 
separate operating guidelines for this IRC with all the necessary details are given in the IRC 
Charter.
7.2. Interim Analyses and Summaries
The decision at the end of the study is being at least 90% confident that active treatment will 
be superior to placebo.  The study will be stopped for futility for the active treatment arm if 
the conditional power with respect to the final analysis at the end of study is <10%.  The
details of conditional power computation will be given in the IRC. Due to the nature of the 
analyses the overall Type 1 error for the study is maintained.  If the futility condition is met, 
the study will be stopped at the interim point.  The interim analysis results will be used to 
facilitate internal decision-making.  The results will only be distributed to a select list of 
individuals involved in the internal decision-making process in order to protect the integrity 
of the study.  This list of individuals will be provided in the IRC charter.  The results of the 
interim analysis will not enable individuals directly involved in running the study (such as 
investigators) to identify treatment assignments for individual subjects still in the study.  
There are no prospective plans to stop the study early for success as a result of the interim 
analyses.
During the interim analysis, some members of the study team may be unblinded and replaced 
with blinded colleagues.  The subjects, investigators, and individuals from the sponsor (or 
designee) who interact with the investigators and monitor safety will continue to be blinded 
to individual study treatments throughout the study.  


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8. REFERENCES 
1.
Chan ISF., Zhang Z. Test-based exact confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999; 55: 1201–1209.
2.
Dmitrienko, A., Molenberghs, G., Chuang- Stein, C., Offen, W. (2005). Analysis of 
Clinical Trials Using SAS: A Practical Guide. Cary, NC: SAS Institute Inc.
3.
Jairath V, Zou G, Parker CE, et al. Systematic review with meta-analysis: placebo rates 
in induction and maintenance trials of ulcerative colitis. J Crohns Colitis 2016; 
10(5):607.


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9. APPENDICES
Appendix 1. Summary of Efficacy Analyses
Efficacy analyses comparing active and placebo arms will be based on the mITT and PP 
population.
Efficacy Endpoints
Analysis 
Method
Missing
Data
Proportion of subjects achieving Clinical Remission at Week 12
Chan and 
Zhang
TFA
Proportion of subjects achieving Clinical Remission at Week 12
Chan and 
Zhang
OC
Proportion of subjects with endoscopic improvement at Week 12
Chan and 
Zhang
OC
Proportion of subjects with endoscopic improvement at Week 12
Chan and 
Zhang
TFA
Mean change from baseline at Week 12 in Geboes histology score. ANCOVA
BOCF
Proportion of subjects with a clinical response at Week 12
Chan and 
Zhang
TFA
Proportion of subjects with a clinical response at Week 12
Chan and 
Zhang
OC
Proportion of subjects with change from baseline in partial Mayo 
Score of 2 with no individual subscore >1 at Weeks 2, 4, 6, 8, 12.
MMRM
OC
Plasma concentrations of PF-06687234 over time
MMRM
OC
Incidence of the development of  HAFAs and Nabs against 
PF-06687234.
GLMM
OC
Change from baseline in serum hsCRP levels over time
MMRM
OC
Change from baseline in fecal calprotectin over time
MMRM
OC


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Appendix 2. Definition and Use of Visit Windows in Reporting
Visit windows will be used for efficacy variables, and for any safety data that 
display/summarize by study visit.  For other endpoints (eg, ECG, vital signs), visit windows 
will be applied for summary statistics by study visits if required.
Visit Label
Target Day
Definition [Day window]
Screening
Days -28 to Day 0
Induction Period Weeks 0-12
Week 0
Day 1, Baseline
Day 1
Week 2
15
Days 2 to 21
Week 4
29
Days 22 to 42
Week 8
57
Days 43 to 70
Week 12
85
Days 71 to 98
For the lab values, if the calculated study day for the labelled baseline visit is not study 
Day 1, but falls within 28 days before the start of the study dosing, then that data should be 
used for the baseline instead of leaving baseline missing.
For the other values, if the calculated study day for the labelled baseline visit is not study 
Day 1, but falls before the start of the study dosing, then that data should be used for the 
baseline instead of leaving baseline missing.
If two or more visits fall into the same window, keep the one closest to the Target Day.  If 
two visits are equaled distant from the Target Day in absolute value, the later visit should be 
used.
Safety analysis will follow Pfizer standards.


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Appendix 3. SAS Program Details
Appendix 3.1. Estimate and Confidence Interval of a binomial proportion 
(Blyth-Still-Casella)
PROC BINOMIAL DATA=<DATASET> ALPHA=<value>;
BI/BS;
OU <RESPONSE VARIABLE>;
RUN;
Appendix 3.2. Estimate and Confidence Interval for Risk Difference
Appendix 3.2.1. SAS code for the Confidence Interval for Risk Difference using Chan 
and Zhang (1999)
PROC BINOMIAL DATA=<DATASET> GAMMA=0 ALPHA=<Value>;
PD/EX ONE STD;
PO <POPULATION VARIABLE>;
OU <OUTCOME VARIABLE>;
RUN;
Appendix 3.2.2. SAS Code for GLIMMIX Analysis for Binary Data Analysis with 
Multiple Timepoints
PROC GLIMMIX DATA =<DATA> METHOD=RMPL ;
CLASS SUBJID TRTPN VISIT ;
MODEL RESPONSE (EVENT = "1") = TRTPN VISIT TRTPN * VISIT / ALPHA = 
<ALPHA> DIST=BINARY LINK=LOGIT;
RANDOM VISIT /SUBJECT = SUBJID TYPE=UN  RESIDUAL ;
LSMEANS TRTPN * VISIT / ILINK COV DIFF CL;
RUN;
Appendix 3.2.3. SAS Code for LMMs
PROC MIXED DATA=_DATA; 
CLASS TREATMENT SUBJID TIME;
MODEL EFFICACYCHANGE =TREATMENT BASELINE TIME 
TIME*TREATMENT/DDFM=KR SOLUTION;
REPEATED TIME/ TYPE=UN SUBJECT=SUBJID;
RUN;


Protocol B7581002 (PF-06687234) 
Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 27
Appendix 3.2.4. SAS Code for ANCOVA Models
PROC MIXED DATA=_DATA; 
CLASS TREATMENT; 
MODEL EFFICACYCHANGE = TREATMENT BASELINE /DDFM=KR SOLUTION; 
RUN;