Clinical trial NCT05107492
Conditions: Inflammatory Bowel Disease
Keywords: IBD PK
Sponsor: Pfizer
Start date: 2021-11-19; Completion date: 2022-04-09
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 1, single-center, randomized, double-blind, third-party open (ie, participant blind, investigator blind and sponsor open), placebo controlled study to investigate PK, safety, tolerability, immunogenicity, and PD of PF 06480605 following a single subcutaneous dose of PF-06480605 450 mg and 150 mg (if needed) in Chinese healthy adult participants.

Detailed description:

Arms: arm 1: 12 participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment 450mg and placebo arms. arm 2: 12 participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment 150mg and placebo arms.
Interventions: intervention 1: 450mg intervention 2: 150mg intervention 3: Placebo
Intervention descriptions: intervention 1: following a single subcutaneous dose of PF-06480605 450 mg intervention 2: following a single subcutaneous dose of PF-06480605 150 mg intervention 3: following a single subcutaneous dose of placebo

Protocol documents:
Prot_000.pdf: 
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A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE PHARMACOKINETICS, 
SAFETY AND TOLERABILITY FOLLOWING SINGLE SUBCUTANEOUS DOSE 
OF PF-06480605 IN CHINESE HEALTHY PARTICIPANTS
Study Intervention Number:
PF-06480605
Study Intervention Name:
N/A
US IND Number:
N/A
EudraCT Number:
N/A
Protocol Number:
B7541013
Phase:
1
Short Title: Evaluation of the pharmacokinetics, safety and tolerability of single dose of 
PF-06480605 in Chinese healthy participants
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
29 Dec 2020
N/A
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ....................................................................................................................10
1.3. Schedule of Activities .............................................................................................11
2. INTRODUCTION ...............................................................................................................14
2.1. Study Rationale .......................................................................................................14
2.2. Background .............................................................................................................14
2.2.1. Nonclinical Overview.................................................................................14
2.2.2. Clinical Overview.......................................................................................14
2.2.2.1. Safety.........................................................................................15
2.2.2.2. Immunogenicity ........................................................................17
2.2.2.3. Pharmacokinetics ......................................................................18
2.3. Benefit/Risk Assessment.........................................................................................20
2.3.1. Risk Assessment.........................................................................................20
3. OBJECTIVES AND ENDPOINTS.....................................................................................21
4. STUDY DESIGN.................................................................................................................21
4.1. Overall Design.........................................................................................................21
4.2. Scientific Rationale for Study Design.....................................................................22
4.3. Justification for Dose ..............................................................................................23
4.4. End of Study Definition ..........................................................................................24
5. STUDY POPULATION......................................................................................................25
5.1. Inclusion Criteria.....................................................................................................25
5.2. Exclusion Criteria....................................................................................................25
5.3. Lifestyle Considerations..........................................................................................29
5.3.1. Meals and Dietary Restrictions...................................................................29
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................29
5.3.3. Activity .......................................................................................................30
5.3.4. Contraception..............................................................................................30
5.4. Screen Failures ........................................................................................................30
6. STUDY INTERVENTION..................................................................................................30
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6.1. Study Intervention(s) Administered........................................................................30
6.1.1. Administration............................................................................................31
6.2. Preparation/Handling/Storage/Accountability ........................................................31
6.2.1. Preparation and Dispensing........................................................................32
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................33
6.3.1. Allocation to Study Intervention ................................................................33
6.3.2. Breaking the Blind......................................................................................33
6.4. Study Intervention Compliance...............................................................................34
6.5. Concomitant Therapy..............................................................................................34
6.6. Dose Modification...................................................................................................34
6.7. Intervention After the End of the Study..................................................................34
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................35
7.1. Discontinuation of Study Intervention ....................................................................35
7.2. Participant Discontinuation/Withdrawal From the Study.......................................36
7.2.1. Withdrawal of Consent...............................................................................36
7.3. Lost to Follow up ....................................................................................................37
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................37
8.1. Efficacy Assessments..............................................................................................38
8.2. Safety Assessments .................................................................................................38
8.2.1. Physical Examinations................................................................................38
8.2.2. Chest Radiography......................................................................................39
8.2.3. Vital Signs ..................................................................................................39
8.2.3.1. Temperature ..............................................................................39
8.2.4. Electrocardiograms.....................................................................................39
8.2.5. Clinical Safety Laboratory Assessments ....................................................40
8.2.6. Pregnancy Testing ......................................................................................41
8.2.7. Injection Site Reactions..............................................................................41
8.3. Adverse Events and Serious Adverse Events..........................................................41
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......42
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................42
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................43
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8.3.2. Method of Detecting AEs and SAEs ..........................................................43
8.3.3. Follow -up of AEs and SAEs......................................................................43
8.3.4. Regulatory Reporting Requirements for SAEs...........................................43
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................44
8.3.5.1. Exposure During Pregnancy......................................................44
8.3.5.2. Exposure During Breastfeeding ................................................45
8.3.5.3. Occupational Exposure .............................................................46
8.3.6. Cardiovascular and Death Events...............................................................46
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................46
8.3.8. Adverse Events of Special Interest.............................................................46
8.3.8.1. Lack of Efficacy........................................................................46
8.3.9. Medical Device Deficiencies......................................................................46
8.3.10. Medication Errors.....................................................................................46
8.4. Treatment of Overdose............................................................................................47
8.5. Pharmacokinetics ....................................................................................................48
8.6. Pharmacodynamics..................................................................................................49
8.7. Genetics...................................................................................................................49
8.7.1. Specified Genetics ......................................................................................49
8.8. Biomarkers ..............................................................................................................50
8.9. Immunogenicity Assessments.................................................................................50
8.10. Health Economics .................................................................................................50
9. STATISTICAL CONSIDERATIONS ................................................................................50
9.1. Statistical Hypotheses .............................................................................................51
9.2. Sample Size Determination.....................................................................................51
9.3. Analysis Sets ...........................................................................................................52
9.4. Statistical Analyses .................................................................................................52
9.4.1. General Considerations...............................................................................52
9.4.2. Primary Endpoint(s)....................................................................................52
9.4.2.1. Electrocardiogram Analyses......................................................53
9.4.3. Secondary Endpoint(s)................................................................................54
9.5. Interim Analyses .....................................................................................................55
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9.6. Data Monitoring Committee or Other Independent Oversight Committee.............55
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................56
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............56
10.1.1. Regulatory and Ethical Considerations ....................................................56
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................56
10.1.2. Financial Disclosure .................................................................................57
10.1.3. Informed Consent Process ........................................................................57
10.1.4. Data Protection .........................................................................................58
10.1.5. Dissemination of Clinical Study Data ......................................................58
10.1.6. Data Quality Assurance ............................................................................59
10.1.7. Source Documents....................................................................................61
10.1.8. Study and Site Start and Closure ..............................................................61
10.1.9. Publication Policy.....................................................................................62
10.1.10. Sponsor’s Qualified Medical Personnel .................................................62
10.2. Appendix 2: Clinical Laboratory Tests .................................................................64
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................66
10.3.1. Definition of AE .......................................................................................66
10.3.2. Definition of SAE.....................................................................................67
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................68
10.3.4. Reporting of SAEs....................................................................................71
10.4. Appendix 4: Contraceptive Guidance ...................................................................73
10.4.1. Male Participant Reproductive Inclusion Criteria....................................73
10.4.2. Female Participant Reproductive Inclusion Criteria.................................73
10.4.3. Woman of Childbearing Potential ............................................................73
10.4.4. Contraception Methods.............................................................................74
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow -up.............................76
10.6. Appendix 6: ECG Findings of Potential Clinical Concern ...................................78
10.7. Appendix 7: Abbreviations ...................................................................................80
11. REFERENCES ..................................................................................................................84
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LIST OF TABLES
Table 1.
Randomization Scheme ............................................................................22
Table 2.
Serum PF-06480605 Pharmacokinetic Parameters (Primary 
endpoints) .................................................................................................53
Table 3.
Serum PF-06480605 Pharmacokinetic Parameters (Secondary 
endpoints) .................................................................................................54
Table 4.
Protocol-Required Safety Laboratory Assessments .................................64
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: Evaluation of the pharmacokinetics, safety and tolerability of single dose of 
PF-06480605 in Chinese healthy participants
Rationale
The purpose of this study is to evaluate the PK, safety, tolerability, immunogenicity, and PD 
of PF-06480605 in Chinese healthy adult participants. The information of the PK, safety, 
tolerability, immunogenicity, and PD in Chinese healthy participants is being collected to 
support further clinical development as well as drug registration in China. Characterizing PK 
in Chinese participants is set as one of the primary objectives in order to meet the 
requirement of CDE.
Objectives and Endpoints
Objectives
Endpoints
Primary:
Primary:
•
To characterize the PK of PF-06480605
following administration of single SC dose of 
PF-06480605 450 mg and 150 mg (if needed) 
in Chinese healthy adult participants.
•
To evaluate the safety and tolerability 
following administration of single SC dose of 
PF-06480605 450 mg and 150 mg (if needed) 
in Chinese healthy adult participants
•
Serum PF-06480605 primary PK parameters, as
permitted by data: Cmax, Tmax, AUC14 days, AUCinf,
and t½.
•
Assessment of AEs, vital signs, 12 lead 
electrocardiograms, physical examination 
findings, and clinical safety laboratory 
measurements
Secondary:
Secondary:
•
To further evaluate the PK of PF-06480605
•
To evaluate the immunogenicity of 
PF-06480605.
•
To evaluate the PD biomarker (if 
feasible) which may be informative in 
demonstrating the pharmacologic effect 
of PF-06480605.
•
Serum PF-06480605 PK parameters, as
permitted by data: AUClast, Cmax(dn),
AUCinf(dn), AUClast(dn), Vz/F, and 
CL/F.
•
Incidence of the development of ADA and 
NAb.
•
Total sTL1A protein concentration in serum.
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Overall Design
This is a Phase 1, single-center, randomized, double-blind, third-party open (ie, participant 
blind, investigator blind and sponsor open), placebo-controlled study to investigate PK, 
safety, tolerability, immunogenicity, and PD of PF-06480605 following a single 
subcutaneous dose of PF-06480605 450 mg and 150 mg (if needed) in Chinese healthy adult
participants. Optional 150 mg cohort will be conducted only if data from the 450 mg cohort
do not confirm expected PK based on previous studies in healthy Western and Japanese 
participants as well as UC patients.
Number of Participants
A maximum of approximately 24 participants (18 with active treatment and 6 with placebo)
will be randomized and receive the study intervention such that approximately 
12 participants are assigned to each cohort (450 mg and 150 mg) to ensure that 11 evaluable
participants per cohort will complete the study. Participants, who drop out from the study if 
the number of participants completing at least the follow-up visit at Day 57 per cohort
decreases to 10 or lower, will be replaced.
Intervention Cohorts and Duration
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single dose of PF-06480605 450 mg or 150 mg (if 
needed) or placebo. Participants will be admitted into the clinical research unit (CRU) 
approximately 1 day prior to dosing and required to stay overnight in the CRU at least through 
completion of the Day 5 evaluations. Participants will return for outpatient follow-up visits 
through Day 114.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
The maximum sample size of approximately 24 participants is not based on any statistical 
considerations. Those participants will be enrolled and receive the study intervention such 
that approximately 12 participants are assigned to each cohort (450 mg and 150 mg) to 
ensure that 11 evaluable participants per cohort will complete the study. In each cohort, 
12 participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment 
and placebo arms.
Participants will be enrolled to both cohorts sequentially, starting with the 450 mg cohort
first. When the 150 mg cohort is determined to be needed, the 150 mg cohort with entirely 
new participants will be opened. The 150 mg cohort will be started only if it indicates the 
ethnic PK difference (eg, more than two-fold higher exposure) based on all available serum 
concentrations data of PF-06480605 obtained until the timing the PK sample is collected at 
Day 14 after administration, by comparing the dose-normalized mean exposures (or 
dose-normalized mean concentrations profiles) in this study versus dose-normalized mean 
exposures in Western study B7541001 and Japanese study B7541006. If the 150 mg is not 
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needed, then only approximately 12 participants will be administered the study intervention
or placebo.
Cohort
Treatment
Number of participants
1
PF-06480605 450 mg
9
Placebo
3
2 (optional)
PF-06480605 150 mg
9
Placebo
3
Participants, who dropout from the study if the number of participants completing at least the 
follow-up visit at Day 57 per cohort decreases to 10 or lower, will be replaced.
If a participant discontinues before completing the part of the study to which they have been 
randomized, or withdraws for reasons unrelated to the safety of the study intervention, the 
participant may be replaced at the discretion of the investigator upon consultation with the 
sponsor.
Serum concentrations and serum PK parameters will be summarized descriptively. 
Safety and tolerability data will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations.
Overall incidence of development of ADA and NAb will be reported by incidence with
respect to time. Both titer and positive/negative will be reported for the ADA and NAb 
assays by time points samples were collected.
The total sTL1A protein concentration in serum will be summarized by time and presented in 
a tabular or graphical form.
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor will conduct unblinded reviews of the data of 450 mg SC cohort through Day 14 
during the course of the study for the purpose of determining whether or not to conduct 
150 mg SC cohort, and preliminarily assess any ethnic differences between Chinese and non-
Chinese, thus to support China joining further global Phase 2 and/or Phase 3 studies.
1.2. Schema
Not applicable.
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section 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 in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Identifiera
Abbreviations used in this table may be found in 
Appendix 7.
Screen
CRU confinement
Follow-up visitsb
Days Relative to Day 1
-28 to -
2
-1
1
2
3
4
5
10
15
29
43
57
85
114
/ET
Hours After Dose
-
-
0
1
c
2
c
6
c
24c
48c
72c
96c
-
-
-
-
-
-
-
Informed consent & demography
X
CRU confinement
X
→
→
→
→
→
→
→
X
Visit to the CRU
X
X
X
X
X
X
X
X
X
Inclusion/exclusion criteria
X
X
Medical/medication history
X
X
Review alcohol/tobacco
X
X
Report prior or concomitant treatments
X
X
→
→
→
→
→
→
→
→
X
X
X
X
X
X
X
Contraception check
X
X
X
X
X
X
X
X
X
Physical exam (including height & body 
weight at Screen, only)d
X
X
12-Lead ECG (single)
X
X
X
X
X
Supine blood pressure, pulse rate and temperature
X
X
X
X
X
Chest radiographse
X
Adverse event monitoring
X
→
→
→
→
→
→
→
→
X
X
X
X
X
X
X
X
Study treatment administration
Xf
Injection Site Reaction
Xf
Xf
Xf
Blood sample for
Safety laboratory (after ≥4 h fast) (refer to 
Section 10.2)
X
Xg
X
X
X
X
X
X
X
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Visit Identifiera
Abbreviations used in this table may be found in 
Appendix 7.
Screen
CRU confinement
Follow-up visitsb
Days Relative to Day 1
-28 to -
2
-1
1
2
3
4
5
10
15
29
43
57
85
114
/ET
Hours After Dose
-
-
0
1
c
2
c
6
c
24c
48c
72c
96c
-
-
-
-
-
-
-
Serum FSH in females amenorrheic ≥12 months, 
onlyh
X
Serum Pregnancy test (WOCBP only)i
X
Xg
HIV, HBcAb, HBsAb, HBsAg, HCVAb and syphilis
X
HBVDNA (refer to Section 5.2)j
X
X
X
Interferon Gamma Release Assay (IGRA)k
X
X
COVID-19 testl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Pharmacokinetic blood sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Soluble TL1A
X
X
X
X
X
X
X
X
Immunogenicity (ADA, NAb)
X
X
X
X
X
X
Urine Samples for
Urine drug testing
X
Xg
Urine pregnancy test (WOCBP only)i
X
X
X
X
Urinalysis
X
Xg
X
X
X
X
X
X
X
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Visit Identifiera
Abbreviations used in this table may be found in 
Appendix 7.
Screen
CRU confinement
Follow-up visitsb
Days Relative to Day 1
-28 to -
2
-1
1
2
3
4
5
10
15
29
43
57
85
114
/ET
Hours After Dose
-
-
0
1
c
2
c
6
c
24c
48c
72c
96c
-
-
-
-
-
-
-
a.
Day relative to start of study treatment (Day 1).
b.
Procedure are completed within ±3 days.
c.
Procedures are completed within ±10% of the collection time (ie, 2 hours ±12 minutes; 6 hours ±36 minutes, etc).
d.
A full physical examination may be done at screening or Day -1. Brief physical examination to follow up open AEs after Day -1 may be done.
e.
Chest X-ray or other appropriate diagnostic imaging (ie, CT or MRI) should be performed at screening (unless taken within 3 months prior to the screening). Chest X-rays
are required and should be performed as per local guidelines and standard of care (eg, posterior anterior and lateral views). Official reading must be located in the source
documentation.
f.
Participants should be monitored for a minimum of 2 hours after administration of PF-06480605 to assess the injection site.
g.
Test results must be reviewed by a physician and deemed acceptable in order to proceed with participation in study.
h.
A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or HRT.
i.
Serum or Urine Pregnancy tests must have a sensitivity of at least 25 mIU/mL. See Section 8.2.6.
j.
If HBsAg is negative, HBcAb is negative, HBsAb is positive, and no unequivocal documentation of prior HBV vaccination is available or HBsAg is negative, HBcAb is
positive, and HBsAb is positive, the participant is required to undergo HBVDNA reflex testing at screening. If HBVDNA is undetectable in the HBVDNA reflex testing in
screening and the participant is enrolled the study, HBVDNA testing must be performed on Day 57 and 114/ET.
k.
Acceptable IGRA assays are QuantiFERON®-TB Gold In Tube (QFT-G) test and T-SPOT®.TB (T-Spot) test. A documented TB test performed within 12 weeks prior to 
Day 1 is acceptable. Participants with a history of tuberculosis may not require TB testing as per the protocol exclusion criteria in Section 5.2 Exclusion Criteria 6. A 
negative PPD test can be substituted for the QFT-G test or T-Spot test only under specific circumstances described in Section 5.2, Exclusion Criteria 6. For subject with 
negative TB test at screen, TB test can be repeated at Day 114.
l.
Testing for active COVID-19 infection, including testing methodology and frequency will follow CRU’s practice. These tests may not be needed if the pandemic is over. 
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2. INTRODUCTION
PF-06480605 is a fully human IgG1 monoclonal antibody against TL1A, a member of the 
TNF family of cytokines, that is currently in development for the treatment of CD and UC. 
The mechanism of action of PF-06480605 is to neutralize the binding and subsequent 
signaling of TL1A to its functional receptor DR3 on immune cells of the innate and adaptive 
immune system.
2.1. Study Rationale 
The purpose of the study is to evaluate the PK, safety, tolerability, immunogenicity, and PD 
of PF-06480605 in Chinese healthy adult participants. The information of the PK, safety, 
tolerability, immunogenicity, and PD in Chinese healthy participants is being collected to 
support further clinical development as well as drug registration in China. 
2.2. Background 
TL1A is a member of the TNF family of cytokines also known as TNF sub-family 15.
TL1A is a ligand for its functional receptor DR3, also known as TNF receptor 
sub-family 25.1 TL1A expression on antigen presenting cells (monocytes, macrophages, 
dendritic cells) and DR3 expression on effector cells (T cells, NK and NKT cells) is highly
dependent on pro-inflammatory conditions. 2,3,4 In vivo and in vitro evidence support a
co-stimulatory role for the TL1A/DR3 pathway on T cells and in enhancing effector cell 
functions, inflammatory cell expansion and cytokine secretion. In agreement, this pathway
has been implicated in the regulation of pathogenic Th1, Th2, Th9, and Th17 T-helper 
responses, and of ILC2, NK and NK-T cell responses, in immune-mediated
diseases.5,6,7,8,9,10,11,12,13 Studies of DR3 or TL1A gene-deficient mice or mice treated with 
anti-TL1A antibodies demonstrate a role for this pathway in a number of autoimmune 
disease models.8,14 Moreover, significant literature data from nonclinical species and 
humans implicate TL1A most prominently in the pathophysiology of IBD. Numerous
genome wide association studies have linked several polymorphisms of the TL1A gene to 
UC and CD in patient populations of Japanese, European, and Asian origin.1,15,16,17,18,19
Additionally, human inflamed IBD tissues show high levels of TL1A and DR3 expression 
and several independent laboratories have demonstrated that antibody blockade of TL1A 
prevents or attenuates established gut inflammation in a number of murine IBD 
models).4,6,9,20,21,22,23,24,25
2.2.1. Nonclinical Overview
The nonclinical safety profile of PF-06480605 has been adequately characterized in vitro and
in mice, New Zealand White rabbits, and cynomolgus monkeys in vivo to support chronic 
administration in clinical trials.
Further details are provided in the current IB.
2.2.2. Clinical Overview
To date (24 Dec 2020), the clinical development programs for PF-06480605 comprise FIH
study in healthy adult participants (B7541001; SAD and MAD study; completed), phase 1 
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study in Japanese healthy adult participants (B7541006; single subcutaneous dose at two 
dose levels; clinically completed), and a phase 2a study in participants with UC (B7541002; 
open label study; completed). Refer to the IB for more details on the clincial information 
with PF-06480605.
2.2.2.1. Safety 
2.2.2.1.1. B7541001
The B7541001 study was a Phase 1, randomized, double-blind, third-party open, 
placebo-controlled, single and multiple dose escalation study to evaluate the safety and 
tolerability of the single and multiple dose of PF-06480605 in healthy adult participants. 
PF-06480605 doses evaluated in the SAD period were: 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 
300 mg, 600 mg, and 800 mg IV doses. The MAD dose cohorts evaluated were: 30 mg, 
100 mg and 300 mg SC (Q2W) × 3 doses, and 500 mg IV (Q2W) × 3 doses.
A total of 92 healthy participants, 60 and 32 participants in the SAD and MAD periods, 
respectively, were assigned to and received study treatment (PF-06480605 or placebo). 
Single doses up to 800 mg IV and multiple doses up to 300 mg SC (Q2W) and 500 mg IV 
(Q2W) were administered. Six (6) participants discontinued from the study: 3 participants 
each from the SAD period and the MAD period, which included 1 placebo participant from 
each period. There were no study discontinuations attributed to treatment-related AEs). There 
were 2 participants who were lost to follow-up; one participant in the SAD PF-06480605 
100 mg cohort and 1 participant in the SAD PF-06480605 600 mg cohort. Additionally, there 
were 2 participants who were no longer willing to participate in the study; one participant in 
the MAD PF-06480605 30 mg cohort and 1 participant in the SAD placebo cohort.
One participant in the MAD placebo cohort discontinued due to other reasons (withdrawn at 
investigator request, non-AE).
There were no deaths, SAEs, severe AEs, AEs resulting from ADA/NAbs, or participants 
with dose reduced or temporary discontinuations due to AEs during the FIH study with 
PF-06480605. Additionally, there were no clinically significant laboratory abnormalities, 
vital signs, or ECGs. 
In the single dose period, there were 45 all-causality TEAEs reported by 21 participants out 
of the 44 participants treated with PF-06480605. Of these, 15 events were determined to be 
treatment-related and were reported by 13 participants. There were 20 all-causality TEAEs 
reported by 7 participants out of the 16 participants treated with placebo, of which 9 events 
were determined to be treatment-related and were reported by 5 participants. 
In the multiple dose period, there were 44 all-causality TEAEs reported by 17 participants 
out of the 24 participants treated with PF-06480605. Of these, 21 events were determined to 
be treatment-related and were reported by 11 participants. There were 17 all-causality 
TEAEs reported by all of the 8 participants treated with placebo, of which 6 events were 
determined to be treatment-related and were reported by 5 participants. 
Overall, headache was the most commonly reported all-causality (7 PF-06480605 
participants and 3 placebo participants) and treatment-related (5 PF-06480605 participants) 
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TEAE. The second most commonly reported treatment-related TEAE was abdominal pain 
which was reported by 3 PF-06480605 participants and 1 placebo participant. 
The incidence of TEAEs between cohorts in the SAD period and between cohorts in the 
MAD period was similar. Overall, there was a higher incidence of treatment-related TEAEs 
in the MAD cohorts compared with the SAD cohorts, although the incidence of TEAEs did 
not increase with higher doses of PF-06480605.
The majority of TEAEs were mild in severity. There was a higher incidence of moderate 
severity TEAEs reported by participants in MAD cohorts compared with SAD cohorts. The 
study’s only treatment-related moderated severity TEAE, abdominal pain, was reported by a 
participant from a MAD cohort. There were no severe TEAEs reported. 
There were no participants from the SAD period who discontinued from the study due to an 
AE. In the MAD period, there was 1 participant who discontinued from the study due to a 
treatment- unrelated AE, pyuria, on study Day 14. The event was determined to be mild and 
the participant recovered in one day. 
2.2.2.1.2. B7541002
The B7541002 study was a Phase 2a, multicenter, single arm, open-label, 2-stage study to 
evaluate the efficacy, safety, tolerability and PK of PF-06480605 in participants with 
moderate to severe UC.
A total of 50 participants were enrolled and treated with PF-06480605 500 mg IV Q2W for a 
total of 7 doses in the study. Among the 50 participants treated, 33 (66.0%) participants 
reported at least 1 all-causality TEAEs. The most frequently (≥3) reported all-causality 
TEAEs were Arthralgia and Colitis ulcerative in 6 (12.0%) participants each, Abdominal 
pain, Alopecia, Back pain, Nasopharyngitis, Nausea, and Pharyngitis in 3 (6.0%) participants 
each.
Eight (8, 16.0%) participants among the 33 participants reported treatment-related TEAEs. 
TEAEs reported were Abdominal pain, Acrochordon, Alanine aminotransferase increased, 
Alopecia, Arthralgia, Aspartate aminotransferase increased, Back pain, Diastolic 
hypertension, Haematoma, Headache, Hypertension, Infusion site bruising, Muscle spasms, 
Nausea, Oedema peripheral, Oropharyngeal pain, Pruritus, and Vertigo in 1 (2.0%) 
participant each.
Eight (8) participants had Grade ≥3 laboratory abnormalities. Three (3) participants had 
hematology laboratory abnormalities (lymphocyte count decreased) and 5 participants had 
chemistry laboratory abnormalities (creatine phosphokinase increased, hypokalemia and 
hyponatremia). There were no deaths reported in the study.
There were two participants who discontinued study drug treatment. One participant 
discontinued treatment after 6 doses of study drug due to worsening UC. This participant also 
discontinued the study. One participant discontinued treatment-related to a SAE, alopecia. 
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Within the study, there were 4 SAEs reported. Three of these SAEs resulted from worsening 
of underlying disease activity. The fourth SAE was a case of alopecia /baldness, which was 
reported as related to the study drug by the investigator as an SUSAR but unrelated by the 
sponsor. 
2.2.2.1.3. B7541006
B7541006 is an Phase 1, randomized, double-blind, third-party open (ie, participant-blind, 
investigator-blind and sponsor-open), placebo-controlled, dose escalating clinical study to 
evaluate the safety, tolerability, immunogenicity, PK and PD of PF-06480605 in Japanese 
healthy adult participants. The study consists of 2 cohorts, and 6 participants were
randomized to PF-06480605 and 2 participants were randomized to placebo in each cohort. 
Each participant received PF-06480605 (150 mg or 450 mg) or placebo subcutaneously.
The preliminary data from study B7541006 showed that PF-06480605 was safe and well 
tolerated in Japanese healthy participants receiving either150 mg or 450 mg. Till date
(24 Dec 2020), no deaths, serious AEs, or discontinuations due to AEs was reported in this 
study. All TEAEs were observed in 150 mg cohort and were mild to moderate in severity and 
considered recovered. No vital sign or ECG abnormality was clinical remark judged by the 
investigators in both cohorts.
2.2.2.2. Immunogenicity
2.2.2.2.1. B7541001
The incidence of ADA ranged from 50% to 100% for SAD and MAD cohorts. In participants 
receiving PF-06480605, 56 participants out of 68 participants were considered to be positive 
for ADA. The overall confirmed treatment induced incidence rate was 82.4%; however, there 
were 11 participants for whom PF-06480605 concentrations remained above the assay 
tolerance level throughout the study. For drug tolerance, the assay has the potential to report 
a false negative at drug concentrations higher than the stated amount, which may result in the 
inconclusive ADA results. Positive ADA samples were detected as early as 336 hours 
(14 days) post-dose in the SAD cohorts and on Day 29 in the MAD cohorts.
The incidence of NAb ranged from 0% for 2 SAD and 2 MAD cohorts to 100% for the 3 mg 
IV cohort. In participants receiving PF-06480605, 24 participants out of 68 participants were 
considered positive for NAb. The overall confirmed NAb incidence rate was 35.3%; 
however, there were 43 participants for whom PF-06480605 concentrations remained above 
the assay tolerance level throughout the study. Positive NAb samples were detected as early 
as 672 hours (28 days) post-dose in the SAD cohorts and 1680 hours (70 days) post-dose in 
the MAD cohorts. Where data were available, mean serum PF-06480605 concentrations were 
lower in participants identified as ADA positive, compared to participants identified as ADA 
not-positive, and were even lower in participants with NAb log titer ≥0.70. Differences in 
mean serum PK parameters, namely exposure, between participants identified as ADA 
positive and ADA not-positive as well as between participants with NAb log titer <0.70 and 
≥0.70 were more apparent for participants in MAD cohorts but no direct conclusions were 
able to be drawn from the data.
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2.2.2.2.2. B7541002
The incidence of ADA as analyzed by the ADA assay with acid pretreatment (being different 
from the assay used in study B7541001, positive controls and negative controls were
pre-treated with acetic acid before co-incubation with biotin-labeled PF-06480605 and 
ruthenium-labeled PF-06480605 prepared in neutralization buffer. While a true limit of drug 
tolerance was not demonstrated, the assay tolerated up to 2000 ng/mL at both PC levels 
based strictly on a comparison of these levels to the cutpoint was 82% with titer values 
ranging from 1.31 to 4.42 and 1 value above the assay range (>4.64). Five (5) participants 
(10%) tested NAb positive with the cell-based NAb assay and had relatively low titer values 
ranging from 0.809 to 1.38. Following PF-06480605 administration, the median time to first 
detection of ADA and NAb were 140 and 114 days, respectively. 
The immunogenic impact on PK appeared to be minimal based on the similarity of the PK 
profiles in ADA positive and negative subjects and NAb positive and negative subjects while 
trends of lower sTL1A target engagement starting from Week 8 were observed for ADA and 
NAb positive participants compared to the ADA and NAb negative participants. There were
no statistically significant effects of ADA and NAb status on the endoscopic improvement, 
remission (secondary endpoint), endoscopic remission, or remission (exploratory endpoint) at 
Week 14. However, the small sample size, large variability and the high incidence of ADA 
did not provide sufficient information to make a definitive conclusion on the impact of 
ADA/NAb on the PK, PD and efficacy.
2.2.2.2.3. B7541006
To date (24 Dec 2020), there is no immunogenicity data from study B7541006.
2.2.2.3. Pharmacokinetics
2.2.2.3.1. B7541001
Following single IV infusion dosing of PF-06480605 under fasted conditions at doses 
ranging between 1 mg to 800 mg, the Cmax was observed around 1.5 to 2 hours after the end 
of a 1-hour infusion followed by a multiphasic decline of serum concentrations over time, 
with mean t½ values ranging between 6 to 23 days. Mean t½ values at the lower doses 
appeared to be shorter than those observed at the higher doses which may be due in part to 
sensitivity of the assay (more quantifiable serum concentrations above the limit of 
quantification at later time points for the higher doses) and in part of CL values which were 
appeared to decrease with increasing doses.
Overall, PF-06480605 AUC increased in a greater than dose proportional manner across the 
1 mg to 800 mg dose range, while Cmax appeared to increase in an approximately dose 
proportional manner across the dose range studied. 
Geometric mean PF-06480605 CL values appeared to decrease with increasing doses, with a 
mean estimate of 0.0180 L/hr at the 1 mg dose and 0.00688 L/hr at the 800 mg dose. Vss was 
low, indicating that drug is localized mainly to the vascular compartment with mean values 
ranging between 3.4 to 5.5 L across all doses.
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Following multiple SC dose administration of PF-06480605 at 30-mg, 100-mg, and 300-mg 
doses Q2W for a total of 3 doses, absorption from the site of injection was variable, with 
peak serum concentrations achieved within a median time at which Tmax of 96 to 216 hours 
post-dose on Day 1, 192 to 335 hours post-dose on Day 15, and 48 hours post-dose on 
Day 29. 
Dose normalized PK exposure (as measured by geometric mean AUC from time 0 to time τ, 
the dosing interval [AUCτ] and Cmax) on Day 1 indicated that following SC administration, 
exposure increased in a dose proportional manner with an increase in dose, while exposure 
on Days 15 and 29 trended toward greater than dose proportional increases across the 30 mg 
to 300 mg SC doses. 
CL/F and Vz/F for the 100 mg to 300 mg SC doses (individual values for 30-mg SC dose) on 
Day 29 were approximately similar across all 3 SC doses, with geometric mean CL/F and 
Vz/F values ranging between 0.0131 and 0.0167 L/hr and 8.1 and 8.5 L, respectively. Mean 
t½ values for the SC doses (individual values for 30 mg SC dose) on Day 29 ranged between 
8.7 and 21 days with the longer t½ values observed at the 100 mg and 300 mg doses. Mean 
observed Rac based on geometric mean AUCτ on Day 29 ranged between 2.4 and 3.2, and 
Rac, Cmax based on geometric mean Cmax on Day 29 ranged between 2.3 and 4.2, representing 
the magnitude of accumulation following SC Q2W administration for a total of 3 doses.
Apparent bioavailability/estimate of bioavailability for the SC doses relative to IV dosing (F) 
values based on geometric mean AUCτ for the 30 mg, 100 mg, and 300 mg SC doses on Day 
1 were 47%, 44%, and 42%, respectively, relative to the corresponding IV doses from the 
SAD portion of the study.
Following multiple dose administration of a 500 mg IV dose Q2W for a total of 3 doses, 
higher geometric mean AUCτ, values were observed on Days 15 and 29 compared to Day 1 
with similar Cmax values observed across all dosing days. Mean Rac based on geometric mean 
AUCτ on Day 29 was 2.1, and Rac, Cmax based on geometric mean Cmax on Day 29 was 1.4. CL 
and Vss geometric mean values on Day 29 were 0.00776 L/hr and 5.6 L, respectively. Mean 
t½ was 20 days.
2.2.2.3.2. B7541002
Following multiple dose administration of 500 mg PF-06480605 intravenously Q2W for a 
total of 7 doses in subjects with moderate to severe UC, Cmax was observed around 
1.03 hours after the end of a 1 hour infusion. After the achievement of Cmax, PF-06480605 
serum concentration exhibited a biphasic decline over time, with mean t½ of 19.3 days. 
Geometric mean AUCτ over a dosing interval of 14 days (336 hours) was 
57610000 ng•hr/mL and geometric mean of Cmax value was 263400 ng/mL. The geometric 
mean CL value was 0.00868 L/hr. Vss was low (geometric mean value of 4.69 L), indicating 
that PF-06480605 was primarily distributed in the plasma volume. On average, the PK of 
PF-06480605 in UC patients was generally consistent with the PK concentration-time 
profiles in healthy volunteers.
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2.2.2.3.3. B7541006
Up to 24 Dec 2020, study B7541006 is clinically completed, and only the preliminary PK 
results of Cohort 1 (150 mg SC) are available. The PK of PF-06480605 up to Day 5 in 
Japanese healthy participants was comparable to Western healthy participants.
2.3. Benefit/Risk Assessment
PF-06480605 is not expected to provide any clinical benefit to healthy participants. This 
study is designed primarily to generate safety, tolerability, and pharmacokinetic data in 
Chinese healthy participants for further clinical development. In healthy participants, the 
TL1A/DR3 signaling pathway is expected to be quiescent, therefore, limited PD modulating 
would be expected.
PF-06480605 was determined to be well tolerated and to have an acceptable safety profile in 
the clinical studies.
The overall confirmed treatment induced ADA incidence rate in healthy participants and UC 
patients was approximately 82%. The overall confirmed NAb incidence rate was 35.3% in 
healthy participants and 10% in UC patients.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-06480605 may be found in the investigator’s brochure, which 
is the SRSD for this study.
2.3.1. Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Study Intervention: PF-06480605
Potential risk of infections.
PF-06480605 is an 
immunomodulator and, as such, 
can be associated with the 
potential risk of infections 
(including serious infections), 
opportunistic infections, and viral 
reactivation.
Participants with infection 
history will be excluded (See 
Section 5.2) and the risk of 
infection will be monitored in 
the study.
Potential fetal risk.
Although no fetal toxicity was 
observed at NOAEL level for 
PF-06480605 in rabbits. The
potential effect in human fertility
PF-06480605 is still not clear.
WOCBP who are unwilling or 
unable to use contraception as 
defined in the study protocol 
will be excluded (See 
Section 5.3.4. and Appendix 4).
Potential risk of secreting into 
human milk.
It is not known whether 
PF-06480605 is secreted into 
human milk.
PF-06480605 should not be 
administered to breastfeeding 
women and exposure during 
breastfeeding should be reported 
to Pfizer Safety (See 
Section 8.3.5.2).
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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 
•
To characterize the PK of PF-06480605 following 
administration of single SC dose of PF-06480605 
450 mg and 150 mg (if needed) in Chinese healthy 
adult participants.
•
To evaluate the safety and tolerability following 
administration of single SC dose of PF-06480605 
450 and 150 mg (if needed) in Chinese healthy adult 
participants
•
Serum PF-06480605 primary PK parameters, as 
permitted by data: Cmax, Tmax, AUC14 days, AUCinf, 
and t½.
•
Assessment of AEs, vital signs, 12 lead 
electrocardiograms, physical examination findings 
and clinical safety laboratory measurements
Secondary:
Secondary: 
•
To further evaluate the PK of PF-06480605
•
To evaluate the immunogenicity of PF-06480605.
•
To evaluate the PD biomarker (if feasible) which 
may be informative in demonstrating the 
pharmacologic effect of PF-06480605.
•
Serum PF-06480605 PK parameters, as 
permitted by data: AUClast, Cmax(dn),
AUCinf(dn), and AUClast(dn), Vz/F and 
CL/F.
•
Incidence of the development of ADA and NAb.
•
Total sTL1A protein concentration in serum.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, single-center, randomized, double-blind, third-party open (participant 
blind, investigator blind, sponsor open), placebo -controlled study to investigate PK, safety, 
tolerability, immunogenicity, and PD of PF-06480605 following a single subcutaneous dose 
of PF-06480605 450 mg and 150 mg (if needed) in Chinese healthy adult participants. 
Optional 150 mg cohort will be conducted only if data from 450 mg cohort does not confirm 
expected PK based on previous studies in healthy Western and Japanese participants as well 
as UC patients.
A maximum of approximately 24 participants (18 with active treatment and 6 with placebo) 
will be randomized and receive the study intervention such that approximately 12 
participants are assigned to each cohort (450 mg and 150 mg) to ensure that 11 evaluable 
participants per cohort will complete the study. Participants will be enrolled to both cohorts 
sequentially, starting with the 450 mg cohort first. When the 150 mg cohort is determined to 
be needed, the 150 mg cohort with entirely new participants will be opened.
The 150 mg cohort will be started only if it indicates the ethnic PK difference (eg, more than 
two-fold higher exposure) based on all available serum concentrations data of PF-06480605 
obtained until the timing the PK sample is collected at Day 14 after administration, by 
comparing the dose-normalized mean exposures (or dose-normalized mean concentrations 
profiles) in this study versus dose-normalized mean exposures in Western study B7541001 
and Japanese study B7541006. 
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Table 1.
Randomization Scheme
Cohort
Treatment
Number of participants
1
PF-06480605 450 mg
9
Placebo
3
2 (optional)
PF-06480605 150 mg
9
Placebo
3
Participants, who drop out from the study if the number of participants completing at least 
the follow-up visit at Day 57 per cohort decreases to 10 or lower, will be replaced.
If a participant discontinues before completing the part of the study to which they have been 
randomized, or withdraws for reasons unrelated to the safety of the study intervention, the 
participant may be replaced at the discretion of the investigator upon consultation with the 
sponsor.
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single dose of PF-06480605 450 mg or 150 mg (if 
needed) or placebo. Participants will be admitted into the CRU approximately 1 day prior to 
dosing and required to stay overnight in the CRU at least through completion of the Day 5 
evaluations. Participants will return for outpatient follow-up visits through Day 114.
4.2. Scientific Rationale for Study Design
This Phase 1 study is designed to characterize the PK, safety, tolerability, immunogenicity, 
and PD of PF-06480605 after single SC dose administration in Chinese healthy adult 
participants.
To date (24 Dec 2020), no PK or safety data of PF-06480605 in Chinese are available. 
Although there is no expected relevant PK difference between Chinese and non-Chinese 
(Japanese and Westerners) because monoclonal antibodies are generally known that the 
absence of ethnic differences in their distribution and elimination, similar to that of 
endogenous IgG26 , characterizing PK in Chinese participants is set as one of the primary 
objectives in order to meet the requirement of CDE on the application for China joining in 
global Phase 2 study B7541007. Furthermore, the safety and tolerability of PF-06480605 in 
human was already confirmed and concluded as well-tolerated in non-Chinese participants,
however, in order to confirm the safety and tolerability of PF-06480605 in Chinese healthy 
participants prior to administer PF-06480605 to Chinese patients, establishing safety and 
tolerability of PF-06480605 in Chinese healthy participants is set as co-primary objective.
Corresponding endpoints are set as the same as the PK and safety assessments of Study 
B7541001 in Westerners and Study B7541006 in Japanese.
Regarding the secondary objectives and the secondary endpoints, the further PK evaluation 
and the immunogenicity evaluation are set in this study, which allows to compare the results 
of PK and immunogenicity of PF-06480605 in Western healthy participants in Study 
B7541001 and Japanese healthy participants in Study B7541006.
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Total sTL1A protein concentration in serum will be evaluated to confirm the target 
engagement and the consistency with the results in Study B7541001 and Study B7541006.
The study duration and frequency of each assessment were decided based on information of 
previous studies. Day 114 was considered the necessary period to reduce blood levels 
sufficiently, and no treatment-related AEs were observed after Day 85 in previous studies. 
Sample collection points for PK, immunogenicity and PD were selected based on the results 
in Study B7541001 and/or Study B7541006. In addition, based on considering the clinical 
practice and minimal neccitiy for PK evaluation, participants, who drop out from the study if 
the number of participants completing at least the follow-up visit at Day 57 per cohort 
decreases to 10 or lower, will be replaced.
It is common to use a double-blind design (participant- and investigator-blinded) with 
placebo control to evaluate the safety and tolerability of the drug, while sponsor is open to 
allow more efficient decision-making, especially in early stage of the development.
In the definitive EFD study, PF-06480605 was intravenously administered by bolus injection 
to pregnant New Zealand White female rabbits once daily on GD 7 and 14 at 0, 60, 180, or 
500 mg/kg/dose. The maternal and developmental NOAEL for PF-06480605 in rabbits was 
the highest dose tested, 500 mg/kg/dose, based on a lack of test article-related effects. Also, 
there were no findings in male or female reproductive organs in the 3- or 6-month toxicity 
studies in mice and cynomolgus monkeys, respectively. It is not known whether 
PF-06480605 can affect male fertility or whether PF-06480605 is secreted in human milk. 
Because of the investigational nature of this product, PF-06480605 should not be
administered to pregnant women or women who are nursing an infant. Given the unlikely 
risk of human teratogenicity/fetal toxicity all acceptable effective methods of contraception 
will be required for approximately 5 half -lives (a minimum of 114 days [±3 days]), 
following the last dose of study intervention (see Appendix 4). The potential risk of exposure 
to PF-06480605 in a sexual partner of a male participant in this study via ejaculate is low, 
and therefore no contraception (condom) use in male participants is warranted. The 
calculated safety margin of 34,852 is >100-fold between the estimated partner exposure due 
to seminal transfer and the NOAEL for serious manifestations of developmental toxicity in 
nonclinical studies. The safety margin of 100fold is based on applying a 10fold safety factor 
for interspecies extrapolation and a 10fold safety factor for susceptible populations.27
4.3. Justification for Dose
In current study, a single SC dose level of 450 mg with an optional lower SC dose of 150 mg 
were selected based on the safety, tolerability, PK and modeling and simulation results in 
previous studies to compare safety and PK among Westerner, Japanese and Chinese. Based 
on results of simulation using a population PK-PD model developed from the combined data 
of Studies B7541001 and B7541002, percentage of patients maintaining Ŏ 90% sTL1A 
coverage throughout the dosing period with 150 mg or 450 mg SC doses every 4 weeks
(Q4W) were > 80%. The dose levels of 450 mg and 150 mg were studied in Japanese healthy 
participant study B7541006, and are being evaluated for the safety and efficacy in Study 
B7541007 in UC patients, while 450 mg is the highest dose used in both studies. An optional 
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dose of 150 mg was selected in case the high dose does not confirm expected PK based on 
previous studies in healthy Western and Japanese participants as well as UC patients. 
As described in Section 2.2.2.1, up to now, single IV doses of up to 800 mg, multiple SC 
doses of up to 300 mg × 3 with 2-week intervals and multiple IV doses of up to 500 mg × 3 
with 2-week intervals were generally safety and well tolerated in Western healthy 
participants in Study B7541001. Apparent bioavailability/estimate of bioavailability for the 
SC doses relative to IV dosing (F) values based on geometric mean AUCǼ for the 30-mg, 
100-mg, and 300-mg SC doses on Day 1 were 47%, 44%, and 42%, respectively, relative to 
the corresponding IV doses from the SAD portion of the study. Dose normalized PK 
exposure (as measured by geometric mean AUCǼ and Cmax) on Day 1 indicated that 
following SC administration, exposure increased in a dose proportional manner with an 
increase in dose, while exposure on Days 15 and 29 trended toward greater than dose 
proportional increases across the 30-mg to 300-mg SC doses.
Considering these results from Study B7541001, exposure following a single 450 mg SC 
dose is much less likely to exceed the exposure of the single 800 mg IV dose observed in 
Study B7541001 and is expected to be safe and tolerable. As expected, the preliminary data 
in Japanese Study B7541006 demonstrated that single dose up to 450 mg SC was clinically 
safe and well tolerated in Japanese healthy participants, and no AE was observed in 450 mg 
cohort. Therefore, the concern of unacceptable safety and tolerability is not expected in 
Chinese healthy participants with administration of  a single 450 mg SC dose.
The preliminarily partial PK data in Japanese Study B7541006 showed no ethic PK 
difference between Japanese and Westerners by comparing the individual concentration-time 
profiles till Day 5 (around Cmax). The full PK profile in Japanese healthy participants will be 
available in Feb/Mar 2021, and the comparison with Western healthy participants will be 
performed afterwards.
Taken together, the likelihood of needing 150 mg cohort is low. 150 mg cohort will be 
conducted only if any of the following scenarios is observed in Chinese healthy participants 
following a single 450 mg SC dose:
•
It indicates the ethnic PK difference (eg, more than two-fold higher exposure) based on 
all available serum concentrations data of PF-06480605 obtained until the timing the PK 
sample at day 14 after administration, by comparing the dose-normalized mean exposures 
(or dose-normalized mean concentrations profiles) in this study versus dose-normalized 
mean exposures in study B7541001 and B7541006, and/or,
•
Sponsor need to initiate 150 mg cohort for other consideration.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the study.
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5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants must be 18 to 45 years of age, inclusive, at the time of 
signing the ICD.
•
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Male and female Chinese participants who are overtly healthy as determined by 
medical evaluation including medical history, physical examination, laboratory tests, 
vital sign and 12-lead ECG.
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
4. BMI of 19 to 27 kg/m2; and a total body weight >50 kg.
Informed Consent:
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
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Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
2. History of HIV infection, hepatitis B, hepatitis C or syphilis; positive testing for HIV, 
hepatitis B, HCVAb or serological reaction of syphilis.  
•
For hepatitis B, all participants must undergo testing for HBsAg, HBcAb, and 
HBsAb. 
o
Participants who are negative for all 3 serology tests may be eligible.
o
Participants who are HBsAg positive will be excluded.
o
HBsAg negative, HBcAb positive, and HBsAb negative particpants are 
to be excluded from the study. 
o
Participants who are HBsAg negative, HBcAb negative and HBsAb 
positive and provide documentation of prior HBV vaccination, may be 
eligible for the study and will not require HBV DNA monitoring during 
the study.
o
Participants who are HBsAg negative, HBcAb negative and HBsAb 
positive without documentation of prior HBV vaccination AND 
participants who are HBsAg negative, HBcAb positive, and HBsAb 
positive, will have HBV DNA assessed at screening.

If HBV DNA is detectable, participants will be excluded.

If HBV DNA is not detectable, participants may be eligible. If 
the participant is included in the study, for subsequent visits 
HBVDNA testing must be performed according to the Schedule 
of Activities. 
3. History of allergic or anaphylactic reaction to a therapeutic drug.
4. History of recent active infections within 28 days prior to the screening visit.
5. Participants with a fever within 48 hours prior to dosing.
6. History of TB or active or latent or inadequately treated infection.
Have evidence of untreated or inadequately treated active or latent Mycobacterium 
TB infection as evidenced by the following:
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a.
A positive QFT-G test or positive or borderline T‑Spot test performed within the 
12 weeks prior to Day 1. If the laboratory reports the test as indeterminate, the test 
should be repeated. A negative PPD test may be substituted for the QFT-G test or 
T-Spot test only with approval from the Pfizer Medical Monitor on a case by case 
basis. For participants with negative QFT-G or T‑Spot test at screen, repeated TB 
test will be perfomed at Day114.
b. Chest radiograph with changes suggestive of active TB infection within 3 months 
prior to Screening. Chest radiograph should be performed according to local 
standards of care or country‑specific guidelines.
c.
History of either untreated or inadequately treated latent or active TB infection.
If a participant has previously received an adequate course of therapy for either 
latent (9 months of isoniazid in a locale where rates of primary multi-drug 
resistant TB infection are <5% or an acceptable alternative regimen) or active 
(acceptable multi-drug regimen) TB infection, neither a QFT-G test, a T-Spot 
test, nor a PPD test need be obtained.  Details of the previous course of therapy 
(eg, medication(s) used, dose, duration of therapy) should be documented in the 
source documentation.
A chest radiograph should be obtained if not done within the 3 months prior to 
Screening. To be considered eligible for the study, the chest radiograph must be 
negative for active TB infection. 
A participant who is currently being treated for active TB infection must be 
excluded from the study.
A participant who is being treated for latent TB infection can only be enrolled 
with confirmation of current incidence rates of multi-drug resistant TB infection, 
documentation of an adequate treatment regimen, and prior approval of the 
Sponsor.
7. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
Prior/Concomitant Therapy:
8. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. (Refer to Section 6.5 for additional details).
9. Recent exposure to live vaccines within 28 days of the screening visit.
Prior/Concurrent Clinical Study Experience:
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10. Known exposure to anti-TL1A (PF-06480605) or any type of anti-TL1A therapy.
11. Previous administration with an investigational drug within 114 days (±3 days) (or as 
determined by the local requirement) or 5 half-lives preceding the first dose of study 
intervention used in this study (whichever is longer). 
Diagnostic Assessments:
12. A positive urine drug test.
13. A positive pregnancy test.
14. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine the participant’s eligibility.
15. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may
affect participant safety or interpretation of study results (eg, baseline QTc interval
>450 msec, complete LBBB, signs of an acute or indeterminate -age myocardial
infarction, ST-T interval changes suggestive of myocardial ischemia, second or 
third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the 
baseline uncorrected QT interval is >450 msec, this interval should be rate
corrected- using the Fridericia method and the resulting QTcF should be used for 
decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, 
the ECG should be repeated 2 more times and the average of the 3 QTc or QRS 
values should be used to determine the participant’s eligibility. Computer
interpreted- ECGs should be overread by a physician experienced in reading ECGs 
before excluding participants.
16. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study specific- laboratory and confirmed by a single 
repeat test, if deemed necessary: 
•
AST or ALT level >1.5 × ULN;
•
Total bilirubin level >1.5 × ULN; participants with a history of Gilbert’s 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ ULN;
•
Hemoglobin level ≤120 g/L (12.0 g/dL);
•
Platelet count ≤150 × 109/L (150,000 cells/mm3);
•
WBC count of ≤3.0 × 109/L (3000 cells/mm3);
•
ANC <1500 cells/mm3;
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•
ALC <800 cells/mm3;
•
eGFR <90 mL/min/1.73 m2 based on the CKD-EPI 2009 equation28;
•
In the opinion of the investigator or Pfizer (or designee), have any clinically 
significant laboratory abnormality that could affect interpretation of study data or 
the participant's participation in the study.
Dianwo dadianhOther Exclusions:
17. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 
5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, 
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
18. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 90 days prior to dosing.
19. History of sensitivity to heparin or heparin -induced thrombocytopenia
20. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
21. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members.
5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Meals and Dietary Restrictions
•
Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations.
•
While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein. The daily caloric intake 
per participant should not exceed approximately 3200 kcal.
5.3.2. Caffeine, Alcohol, and Tobacco
•
Participants will abstain from caffeine -containing products for 24 hours prior to the 
start of dosing and during confinement in the CRU.
•
Participants will abstain from alcohol for 24 hours prior to admission to the CRU and 
continue abstaining from alcohol during confinement in the CRU. Participants may 
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undergo an alcohol breath test or blood alcohol test at the discretion of the
investigator.
•
Participants will abstain from the use of tobacco- or nicotine containing- products for 
24 hours prior to dosing and during confinement in the CRU.
5.3.3. Activity
•
Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted.
5.3.4. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use highly effective contraception consistently and 
correctly and document the conversation and the participant’s affirmation in the participant’s 
chart (participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception). In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the CONSORT publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to PF-06480605 and its placebo.
6.1. Study Intervention(s) Administered
For this study, the study interventions are PF-06480605 and its placebo.
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PF-06480605 is a sterile solution for subcutaneous injection. PF-06480605 will be provided 
in dosage strength of 100 mg/mL in single-use, sterile vials. Each vial contains 200 mg of 
PF-06480605 in 2 mL of solution. Placebo for PF-06480605 will also be provided by Pfizer 
as a sterile liquid solution in single-use, sterile vials.
PF-06480605 and placebo are supplied in a 6 mL glass vial and a 2 mL extractable volume 
with a stopper and aluminum overseal. All vials will be provided in cartons and both will be 
labeled according to local regulatory requirements. The site will take all necessary 
precautions to maintain the investigator and site personnel blind.
6.1.1. Administration
Participants will receive study intervention at approximately 0800 hours (plus or minus 
2 hours). Study medication does not require fasting, but it should be noted that the safety 
laboratory test at Day -1 prior to the study medication need a fast of at least 4 hours. Study 
medication will be administered subcutaneously. Injection should occur at a site on the 
abdomen. All participants will be administered one or more 1.5 mL SC injections. The 
number of SC injections depends on the doses such that one SC injection for 150 mg, and 
three SC injections for 450 mg. Thus, the number of SC injections will be maximal 3 times. 
Each injection is to occur at a different site on the abdomen, approximately 1 cm apart.
Administer study intervention according to the IP manual.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual.
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4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
5. Study interventions should be stored in their original containers and in accordance
with the labels.
6. See the IP manual for storage conditions of the study intervention.
7. Deviations from the storage requirements, including any actions taken, must be 
documented and reported to Pfizer upon discovery. The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible. Once an excursion is identified, the study intervention 
must be quarantined and not used until Pfizer provides permission to use the study 
intervention. It will not be considered a protocol deviation if Pfizer approves the use 
of the study intervention after the temperature excursion. Use of the study 
intervention prior to Pfizer approval will be considered a protocol deviation. Specific 
details regarding the definition of an excursion and information the site should report 
for each excursion will be provided to the site in the IP manual.
8. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site). If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
9. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record.  
10. Further guidance and information for the final disposition of unused study 
interventions are provided in the PCRU’s local/site procedures. All destruction must 
be adequately documented. 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.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff. Dispensing is defined as the provision of study intervention, concomitant treatments, 
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and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol. Local health authority regulations or investigator 
site guidelines may use alternative terms for these activities.
PF06480605 and placebo will be prepared and dispensed by qualified unblinded site 
personnel according to the IP manual. The study intervention will be administered by 
unblinded administrator to the participant. 
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Participants will be randomly assigned to receive study intervention from a central 
randomization scheme. Investigators will remain blinded to each participant’s assigned study 
intervention throughout the course of the study. In order to maintain this blind, an otherwise 
uninvolved third party (for example, pharmacist) will be responsible for the preparation and 
dispensing of all study intervention according to the randomization schedule and assigned 
treatment for the individual participant.
6.3.2. Breaking the Blind
The method for breaking the blind in this study will be manual. A sealed envelope that 
contains the study intervention assignment(s) for each participant will be provided to the 
investigator. The sealed envelope will be retained by the investigator (or representative) in a 
secured area. In case of an emergency, the investigator has the sole responsibility for 
determining if unblinding of a participant’s treatment assignment is warranted. Participant 
safety must always be the first consideration in making such a determination. If the 
investigator decides that unblinding is warranted, the investigator should make every effort to 
contact the sponsor prior to unblinding a participant’s treatment assignment unless this could 
delay further management of the participant. If a participant’s treatment assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. When the 
blinding code is broken, the reason must be fully documented and entered on the CRF/DCT.
Once the study is complete, all envelopes (sealed and opened) must be inventoried and
retained until authorization for destruction has been provided.
Blinding codes should be broken only in exceptional circumstances when knowledge of the 
actual treatment code is absolutely essential for further management of the participant. 
Investigators are encouraged to discuss with a member of the study team if they believe that 
unblinding is necessary. When the blinding code is broken, the reason must be fully 
documented and entered on the CRF/DCT.
This is an investigator- and participant-blind (Sponsor open) placebo-controlled study. Blood 
specimens will be obtained from all participants for PK analysis to maintain the study blind 
at the investigator site. The investigator site staff with the exception of the site pharmacist(s), 
pharmacy assistant(s) and study drug administrator(s) and blinded study monitor, if assigned,
will be blinded to study treatment. Other Pfizer personnel will be unblinded to participant
treatments in order to permit real-time interpretation of the safety and PK data; and provide
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information necessary to potentially alter the dose escalation sequence. The blinded study 
monitor, if assigned, will remain blinded to treatment until all monitoring for the study has 
been completed. Specimens from participants randomized to placebo will not be routinely 
analyzed. To minimize the potential for bias, treatment randomization information will be 
kept confidential by Pfizer unblinded personnel and will not be released to the blinded 
investigator or blinded investigator site personnel until the study database has been locked or 
the investigator requests unblinding for safety reasons.
6.4. Study Intervention Compliance
The study intervention will be administered by investigator site personnel. Deviation(s) from 
the prescribed dosage regimen should be recorded in the CRF.
The site will complete the required dosage Preparation Record located in the IP manual. The 
use of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee.
6.5. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Recent exposure to live vaccines within 28 days of the screening visit is 
prohibited. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤1 g/day.All concomitant treatments taken during the study must be recorded with indication, 
daily dose, and start and stop dates of administration. All participants will be questioned 
about concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention
will be documented as concomitant treatments.
6.6. Dose Modification
Dose modification is not allowed in the current study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following as outlined in Section 7.2.
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for PF-06480605. See the SoA for data to be collected at the time of 
discontinuation of study intervention.
See the SoA for data to be collected at the time of discontinuation of study intervention and 
follow-up for any further evaluations that need to be completed.
Potential Cases of Acute Kidney Injury
Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet 
the criteria below, in the absence of other causes of kidney injury, are considered potential 
cases of acute kidney injury and should be considered important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 μmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness.
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 μmol/L] in SCr
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 μmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury.
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result. This evaluation should include laboratory tests, detailed history, and physical 
assessment. In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices. All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities 
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr. If ≥2 healthy participants are noted to have 2 consecutive SCr results of 
≥0.3 mg/dL (or ≥26.5 μmol/L), an assessment of whether the finding may be considered an 
adverse drug reaction should be undertaken.
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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:
•
Refused further follow-up;
•
Lost to follow-up;
•
Death;
•
Study terminated by sponsor;
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow up- and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.
The participant will be permanently discontinued both from the study intervention and from 
the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1 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.
Lack of completion of all or any of the withdrawal/ET procedures will not be viewed as 
protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol -specified follow -up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow -up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
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information should be used to determine vital status only as appropriately directed in 
accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow -up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
•
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;
•
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;
•
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
A participant who qualified for this protocol but did not enroll from an earlier cohort may be 
used in a subsequent cohort without rescreening, provided laboratory results obtained prior to 
the first dose administration meet eligibility criteria for this study. In addition, other clinical 
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assessments or specimen collections, eg, banked biospecimens, may be used without repeat 
collection, as appropriate.
Every effort should be made to ensure that protocol -required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol -required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter.
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.
The total blood sampling volume for individual participants in this study is approximately 
230 mL. The actual collection times of blood sampling may change. Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 60 consecutive 
days.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1. Efficacy Assessments
Not applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms.
Physical examinations may be conducted by a physician. 
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Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 
surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
8.2.2. Chest Radiography
Chest X-ray (posterior-anterior and lateral views are recommended, however local guidelines 
should be followed) or other appropriate diagnostic image (ie, CT or MRI) should be taken at 
Screening or within 3 months prior to Screening and read by a qualified radiologist or 
pulmonologist and must show no evidence of abnormalities including but not limited to 
current, active TB or previous inactive TB, general infections, heart failure or malignancy. 
Documentation of the official reading must be located and available in the source 
documentation.
8.2.3. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. Participants should be 
instructed not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, 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, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.
8.2.3.1. Temperature
Temperature will be measured according to local practice at times specified in Section 1.3 of 
this protocol. No eating, drinking, or smoking is allowed for 15 minutes prior to the 
measurement.
8.2.4. Electrocardiograms
12-lead ECGs should be collected at times specified in the SoA section of this protocol using 
an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc 
intervals and QRS complex. All scheduled ECGs should be performed after the participant
has rested quietly for at least 10 minutes in a supine position. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements. Additional ECG monitoring will occur if a) a 
postdose QTc interval is increased by ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG. If either of these conditions 
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occurs, then 2 additional ECGs will be collected approximately 2 to 4 minutes apart to 
confirm the original measurement. If the QTc values from these repeated ECGs remain above 
the threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTc interval remains ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner,
at the discretion of the investigator); or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring. A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 6.
8.2.5. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 114 days (瀾3 days) after the last dose of study 
intervention should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
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All protocol required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA.
If laboratory values from nonprotocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
Participants may undergo random urine drug testing at the discretion of the investigator.
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.2.6. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 25 
mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA. Serum 
pregnancy tests will be conducted at screening and pre-dose. Urine pregnancy tests will be 
conducted after dosing mothly over the duration of the study. Following a negative 
pregnancy test result at screening, appropriate contraception must be commenced and a 
second negative pregnancy test result will be required at the baseline visit prior the 
participant’s receiving the study intervention or placebo. Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study. Pregnancy tests may also be 
repeated if requested by IRBs/ ECs or if required by local regulations.
8.2.7. Injection Site Reactions
Each participant will be monitored a minimum of 2 hours after the study intervention. After 2 
hours the injection site will be monitored for redness, swelling, or any type of inflammation 
and this should be recorded as an injection site reaction, if applicable on the appropriate 
CRF. If the participant has a delayed reaction, (after they leave the investigative site) this 
should also be captured as an injection site reaction, on the adverse event CRF page.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 114 calendar days (±3 days) after the administration of the study intervention.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the CRF, not the AE section.
Follow up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AE or SAE after the participant has concluded 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has completed the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator must promptly report the SAE to 
Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form immediately upon awareness and under no circumstance 
should this exceed 24 hours, as indicated in Appendix 3. The investigator will submit any 
updated SAE data to the sponsor within 24 hours of it being available.
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to study 
intervention must be reported to Pfizer Safety.
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8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period
will be recorded on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow -up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow -up (as defined in Section 7.3).
In general, follow -up information will include a description of the event in sufficient detail 
to allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow -up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country -specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
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8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An 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 study 
intervention; or the female becomes or is found to be pregnant after discontinuing 
and/or being exposed to the study intervention;
•
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 
study intervention prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
•
If EDP occurs in a participant or a participant’s partner, 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. Details of the 
pregnancy will be collected after the start of study intervention and until 114 days (瀾
3 days).
•
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
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 
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inspection (unless preprocedure test findings are conclusive for a congenital anomaly and 
the findings are reported).
Abnormal pregnancy outcomes are considered SAEs. 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), 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 including 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 study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further follow
up of birth outcomes will be handled on a case by case basis (eg, follow up on preterm 
infants to identify developmental delays). In the case of paternal exposure, the investigator 
will provide the participant with the Pregnant Partner Release of Information Form to deliver 
to his partner. The investigator must document in the source documents that the participant 
was given the Pregnant Partner Release of Information Form to provide to his partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 
A female participant is found to be breastfeeding while receiving or after discontinuing study 
intervention.
•
A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
•
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so 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.
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An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE. Such persons may 
include healthcare providers, family members, and other roles that are involved in the trial 
participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness regardless of whether there is an associated SAE. The information 
must be reported using the CT SAE Report Form. Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease -Related Events and/or Disease -Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
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Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:
•
Medication errors involving participant exposure to the study intervention;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of PF-06480605 greater than 500 mg within 2-weeks will be 
considered an overdose.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF06480605 (whichever is 
longer).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
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5. Obtain a blood sample for PK analysis within 1 day from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a casebycase
basis). 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics 
Blood samples of approximately 3 mL, to provide approximately 1.2 mL serum, will be 
collected for measurement of serum concentrations of PF-06480605 as specified in the SoA.
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and data collection tool (eg, CRF/DCT). Collection of samples more 
than 10 hours after dose administration that are obtained ≤1 hour away from the nominal 
time relative to dosing will not be captured as a protocol deviation, as long as the exact time 
of the collection is noted on the source document and data collection tool (eg, CRF/DCT). In 
follow-up visits (after Day 5), collection of samples that are obtained within 3 days of 
planned visit will not be captured as a protocol deviations, as long as the exact time of the 
collection is noted on the source document and data collection tool (eg, CRF/DCT).
Samples will be used to evaluate the PK of serum PF-06480605 concentration. Samples 
collected for analyses of serum PF-06480605 concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study, for metabolite 
identification and/or evaluation of the bioanalytical method,
 
Genetic analyses will not be performed on these serum samples. Participant confidentiality 
will be maintained.
Samples collected for measurement of serum concentrations of PF-06480605 will be 
analyzed using a validated analytical method in compliance with applicable SOPs.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (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.
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Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.6. Pharmacodynamics
Blood samples of approximately 8 mL, to provide approximately 3 mL serum, will be 
collected into appropriately labeled collection tubes (no additives). Serum samples will be 
collected and aliquoted for the analysis of serum sTL1A at times specified in the SoA.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and data collection tool (eg, CRF/DCT). Collection of samples more 
than 10 hours after dose administration that are obtained ±1 hour away from the nominal 
time relative to dosing will not be captured as a protocol deviation, as long as the exact time 
of the collection is noted on the source document and data collection tool (eg, CRF/DCT). In 
follow-up visits (after Day 5), collection of samples that are obtained within 3 days of 
planned visit will not be captured as a protocol deviations, as long as the exact time of the 
collection is noted on the source document and data collection tool (eg, CRF/DCT).
As part of understanding the PD of the study intervention, samples may be used for 
evaluation of the bioanalytical method, 
Samples will be analyzed using a validated analytical method in compliance with applicable 
SOPs.
The PD samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PD sample 
handling procedure (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.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
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8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.9. Immunogenicity Assessments
Blood samples of approximately 3 mL, to provide approximately 1.2 mL serum, will be 
collected for determination of anti-drug antibodies (ADA) and neutralizing antibodies (NAb)
as specified in the SoA. Instructions for the collection and handling of biological samples 
will be provided in the laboratory manual or by the sponsor. The actual date and time 
(24-hour clock time) of each sample will be recorded.
Samples collected for determination of anti-drug antibodies (ADA) and neutralizing 
antibodies (NAb) may also be used for additional characterization of the immune response 
and/or evaluation of the bioanalytical method, 
Genetic analyses will not be performed on these serum samples. Participant confidentiality 
will be maintained.
Samples will be analyzed using a validated analytical method in compliance with applicable 
SOPs. Samples determined to be positive for ADA may be further characterized for NAb.
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (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.
Immunogenicity information that would unblind the study will not be reported to investigator 
sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
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modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No formal statistical hypothesis testing will be conducted for PK/PD and safety analyses.
9.2. Sample Size Determination
The maximum sample size of approximately 24 participants is not based on any statistical 
considerations. Those participants will be enrolled and receive the study intervention such 
that approximately 12 participants are assigned to each cohort (450 mg and 150 mg) to 
ensure that 11 evaluable participants per cohort will complete the study. In each cohort, 12 
participants will be randomly assigned at an allocation ratio of 3:1 to the active treatment and
placebo arms.
Participants will be enrolled to both cohorts sequentially, starting with the 450 mg cohort
first. When the 150 mg cohort is determined to be needed, the 150 mg cohort with entirely 
new participants will be opened. The 150 mg cohort will be started only if it indicates the 
ethnic PK difference (eg, more than two-fold higher exposure) based on all available serum 
concentrations data of PF-06480605 obtained until the timing the PK sample is collected at 
Day 14 after administration, by comparing the dose-normalized mean exposures (or dose-
normalized mean concentrations profiles) in this study versus dose-normalized mean 
exposures in Western study B7541001 and Japanese study B7541006. If the 150 mg is not 
needed, then only approximately 12 participants will be administered the study intervention or 
placebo.
Cohort
Treatment
Number of participants
1
PF-06480605 450 mg
9
Placebo
3
2 (optional)
PF-06480605 150 mg
9
Placebo
3
Participants, who drop out from the study if the number of participants completing at least 
the follow-up visit at Day 57 per cohort decreases to 10 or lower, will be replaced.
If a participant discontinues before completing the part of the study to which they have been 
randomized, or withdraws for reasons unrelated to the safety of the study intervention, the 
participant may be replaced at the discretion of the investigator upon consultation with the 
sponsor.
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9.3. Analysis Sets
For purposes of PK and safety analyses, the following analysis sets are defined:
Safety Analysis Set
All randomized participants who applied at least 1 dose of
study intervention.
PK Concentration Set
All randomized participants who applied at least 1 dose of
study intervention and for whom at least 1 concentration value 
is reported.
PK Parameter Set
All randomized participants who applied at least 1 dose of
study intervention and for whom at least 1 of the PK
parameters of interest (eg, AUCinf and Cmax) is calculated.
Immunogenicity
Analysis Set
All randomized participants who applied at least 1 dose of 
study intervention with at least 1 post-treatment anti-drug 
(PF-06480605) antibody determination.
PD Analysis Set
All randomized participants who have at least 1 PD 
assessment.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. General Considerations
No formal statistical tests will be performed. Descriptive analyses or summaries will be 
provided for all endpoints by treatment for each cohort.
Additionally, a population PK model will be developed to characterize the PK and assess the 
effect of ethnicity on PK using all available data. The detailed analysis plans will be 
described in a separate pharmacometric analysis plan.
9.4.2. Primary Endpoint(s)
The primary endpoints consist of PK and safety endpoints. For the PK endpoints, all PK 
analyses will be based on PK concentration (or parameter) set. The following PK parameters
of PF-06480605 will be calculated for each participant, as applicable, using 
noncompartmental analysis of concentration-time data. PK parameters are described in
Table 2.
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Table 2.
Serum PF-06480605 Pharmacokinetic Parameters (Primary endpoints)
Parameter
Definition
Method of Determination
Cmax
Maximum observed concentration
Observed directly from data
Tmax
Time at which Cmax occurred
Observed directly from data as time of first 
occurrence
AUC14 days
Area under the curve from time 0 to 
Day 14 
(336 hours) 
Linear/log trapezoidal method
AUCinfa
Area under the curve from time 0
extrapolated to infinite time
AUClast + (Clast*/kel), where Clast* was the 
predicted serum concentration at the last 
quantifiable time point estimated from the 
log-linear regression analysis
t½a
Terminal elimination half-life
Loge(2)/kel, where kel was the terminal phase 
rate constant calculated by a linear regression 
of the log-linear concentration-time profile
a.
If data permitted. 
Pharmacokinetic parameters were calculated using an internally validated software system, electronic non-compartmental 
analysis (eNCA, version 2.2.4).
Actual PK sampling times will be used in the derivation of PK parameters.
All safety analyses will be performed on the safety analysis set. The safety endpoints include 
Treatment-emergent AEs and SAEs, withdrawals from treatment due to AEs, vital signs, 12 
lead electrocardiograms parameters, and clinical safety laboratory measurements. AEs, 
ECGs, BP, pulse rate, and safety laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of participants. Any clinical laboratory, 
ECG, BP, and pulse rate abnormalities of potential clinical concern will be described. Safety 
data will be presented in tabular and/or graphical format and summarized by treatment for 
each cohort descriptively, where appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted. However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted. Demographic data collected at screening will be reported.
9.4.2.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
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The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of 
Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450 - 480
>480 - 500
>500
Increase from baseline
30 - 60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
9.4.3. Secondary Endpoint(s)
The second endpoints are PK, immunogenicity and PD endpoints, and the PK endpoints are 
shown in Table 4. 
All PK and immunogenicity analyses will be based on PK concentration (or parameter) and 
immunogenicity analysis sets, respectively.
Table 3.
Serum PF-06480605 Pharmacokinetic Parameters (Secondary endpoints)
Parameter
Definition
Method of Determination
AUClast
Area under the curve from time 0 to the time 
of the last quantifiable concentration (Clast)
Linear/log trapezoidal method
Cmax (dn)
Dose normalized Cmax
Cmax/dose
AUClast (dn)
Dose normalized AUClast
AUClast/dose
AUCinf (dn)a
Dose normalized AUCinf
AUCinf/dose
Vz/Fa
Apparent volume of distribution
Dose/(AUCinf*kel)
CL/Fa
Apparent clearance
Dose/AUCinf
a.
If data permitted. 
Pharmacokinetic parameters were calculated using an internally validated software system, electronic non-compartmental 
analysis (eNCA, version 2.2.4).
Serum concentrations and serum PK parameters will be summarized descriptively. 
Safety and tolerability data will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations.
Overall incidence of development of ADA and Nab will be reported by incidence with 
respect to time. Both titer and positive/negative will be reported for the ADA and NAb 
assays by time points samples were collected. Data permitting, the impact of ADA and NAb 
on PK, PD and safety profiles may be explored. 
The total sTL1A protein concentration in serum will be summarized by time and presented in 
a tabular or graphical form. Further details will be documented in the SAP. 
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9.5. Interim Analyses
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor may conduct unblinded reviews of the data of 450 mg SC cohort through Day 14 
and during the course of the study for the purpose of determing whether or not to conduct 
150 mg SC cohort, and preliminarily assess any ethnic differences between Chinese and non-
Chinese, thus to support China joining further global Phase 2 or Phase 3 studies.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC. 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
•
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;
•
Applicable ICH GCP guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:
•
Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;
•
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, 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 participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
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10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study. The participant or his/her legally authorized representative should be given sufficient 
time and opportunity to ask questions and to decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA 
requirements, where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant or his or her legally authorized 
representative is fully informed about the nature and objectives of the study, the sharing of 
data related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
The participant must be informed that his/her personal study -related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant or his or her legally 
authorized representative is fully informed about his or her right to access and correct his or 
her personal data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.
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A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 28 days from the previous ICD signature date.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant -specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer -sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted. These 
results are submitted for posting in accordance with the format and timelines set forth by US 
law.
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EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer -sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in source document agreement).
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
•
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;
•
Inadequate recruitment of participants by the investigator;
•
Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
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Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the Investigator Site Master File.. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent. The contact card contains, at a minimum, protocol and study intervention identifiers, 
participant numbers, contact information for the investigator site, and contact details for a 
contact center in the event that the investigator site staff cannot be reached to provide advice 
on a medical question or problem originating from another healthcare professional not 
involved in the participant’s participation in the study. The contact number can also be used 
by investigator 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 
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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. For 
sites other than a Pfizer CRU, the contact number is not intended for use by the participant
directly, and if a participant calls that number, he or she will be directed back to the 
investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Table 4.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
•
FSHb
•
Urine drug screeningc
•
Pregnancy testd
•
HIV, HBsAg, HBcAb, 
HBsAb, HCVAbe
•
Serology reaction of 
syphilis teste
•
HBV-DNAf
•
Interferon Gamma Release
Assay (IGRA)g
•
Covid-19 testh
Additional Tests 
(Needed for Hy’s Law)
AST, ALT (repeat)
Total bilirubin 
(repeat)
Albumin (repeat)
Alkaline phosphatase 
(repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
GGT
PT/INR
a.
Only if urine dipstick is positive for blood, or leukocyte esterase.
b.
At Screening only, for confirmation of postmenopausal status.
c.
At Screening, the minimum requirement for drug screening includes cocaine, THC, opiates/opioids, 
benzodiazepines, and amphetamines (others are site and study specific).
d.
Serum or urine pregnancy tests for female participants of childbearing potential. Serum pregnancy tests 
will be conducted at screen and pre-dose. Urine pregnancy tests will be conducted after dosing monthly
over the duration of the study.
e.
At Screening only.
f.
If HBsAg is negative, HBcAb is negative, HBsAb is positive, and no unequivocal documentation of 
prior HBV vaccination is available or HBsAg is negative, HBcAb is positive, and HBsAb is positive, the 
participant is required to undergo HBVDNA reflex testing at screening. If HBVDNA is undetectable in 
the HBVDNA reflex testing in screening and the participant is enrolled the study, HBVDNA testing will 
be performed according to the Schedule of Activities.
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Table 4.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
g.
Complete at screening. For subject with negative TB test (IGRA assay) at screen, TB test can be 
repeated at Day 114.
h.
Testing for active COVID-19 infection, including testing methodology and frequency will follow CRU’s 
practice. These tests may not be needed if the pandemic is over.
Investigators must document their review of each laboratory safety report.
Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained and 
stored for the duration of the study. 
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition
•
An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or 
not considered related to the study intervention.
•
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Any 
abnormal laboratory test results that meet any of the conditions below must be 
recorded as an AE:
•
Is associated with accompanying symptoms;
•
Requires additional diagnostic testing or medical/surgical intervention;
•
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.
•
Exacerbation of a chronic or intermittent preexisting condition including either 
an increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration 
even though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
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Events NOT Meeting the AE Definition
•
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms 
of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
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d. Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
•
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
•
Examples of such events include invasive or malignant cancers, 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.
•
Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF 
and for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety.
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; 
and (3) exposure to the study intervention under study during pregnancy or 
breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must 
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be completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and EDP 
supplemental form for 
EDP)
Note: Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.
•
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.
•
The investigator will then record all relevant AE/SAE information in the CRF.
•
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.
•
There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
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•
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.
•
Severe: An event that prevents normal everyday activities. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.
•
A “reasonable possibility” of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out.
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.
•
The investigator will also consult the IB and/or product information, for 
marketed products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the 
sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.
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•
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
•
If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for 
reporting purposes, as defined by the sponsor. 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.
Follow-up of AEs and SAEs
•
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as medically indicated or as 
requested by the sponsor to elucidate the nature and/or causality of the AE or 
SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other 
healthcare providers.
•
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.
•
New or updated information will be recorded in the originally completed CRF.
•
The investigator will submit any updated SAE data to the sponsor within 24 
hours of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool
•
The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as the data
become available.
•
After the study is completed at a given site, the electronic data collection tool 
will be taken off-line to prevent the entry of new data or changes to existing data.
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•
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection 
tool has been taken off-line, then the site can report this information on a paper 
SAE form (see next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form
•
Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.
•
In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated 
reporting time frames.
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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is ≥100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:
•
Is not a WOCBP (see definitions below in Section 10.4.3);
OR
•
Is a WOCBP and using an acceptable contraceptive method as described below 
during the intervention period (for a minimum of 114 days [±3 days] after the last 
dose of study intervention). The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
6. Premenopausal female with 1 of the following:
•
Documented hysterectomy;
•
Documented bilateral salpingectomy;
•
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
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Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study.
7. Postmenopausal female.
•
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, a
•
High FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 
•
Female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion.
5. Vasectomized partner.
•
Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation.
•
Oral;
•
Intravaginal;
•
Transdermal;
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•
Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation.
•
Oral;
•
Injectable.
8. Sexual abstinence.
•
Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow -up
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within 
the same laboratory sample). In rare instances, by the time TBili elevations are detected, 
AST/ALT values might have decreased. This occurrence is still regarded as a potential DILI.
Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:
•
Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.
•
For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
•
Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).
•
Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
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.
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The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology. A detailed history, including relevant information, 
such as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum samples for acetaminophen/paracetamol drug and/or protein adduct levels may be 
warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.6. Appendix 6: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs
•
Marked sinus bradycardia (rate <40 bpm) lasting minutes.
•
New PR interval prolongation >280 msec.
•
New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from 
baseline.
•
New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm.
•
New-onset type I second-degree (Wenckebach) AV block of >30 seconds’
duration.
•
Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs
•
QTcF prolongation >500 msec.
•
New ST-T changes suggestive of myocardial ischemia.
•
New-onset left bundle branch block (QRS >120 msec).
•
New-onset right bundle branch block (QRS >120 msec).
•
Symptomatic bradycardia.
•
Asystole:
•
In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an 
escape rhythm that is below the AV node. 
•
In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 
•
Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.
•
Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).
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•
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm 
(heart rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to
<100 bpm), and monomorphic/polymorphic ventricular tachycardia (HR 
>100 bpm (such as torsades de pointes)).
•
Type II second-degree (Mobitz II) AV block.
•
Complete (third-degree) heart block.
ECG Findings That Qualify as SAEs
•
Change in pattern suggestive of new myocardial infarction.
•
Sustained ventricular tachyarrhythmias (>30 seconds’ duration).
•
Second- or third-degree AV block requiring pacemaker placement.
•
Asystolic pauses requiring pacemaker placement.
•
Atrial flutter or fibrillation with rapid ventricular response requiring 
cardioversion.
•
Ventricular fibrillation/flutter.
•
At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.
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10.7. Appendix 7: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
→
ongoing/continuous event
τ
tau
Abs
Absolute
ADA
anti-drug antibodies
AE
adverse event
ALC
Absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the curve
AUCτ
AUC from time 0 to time τ, the dosing interval
AUC14 days
AUC from time 0 to Day 14 (336 hours)
AUCinf
AUC from time 0 extrapolated to infinite time
AUCinf(dn)
dose normalized AUCinf
AUClast
AUC from time 0 to Tlast
AUClast(dn)
dose normalized AUClast
AV
atrioventricular
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
CD
Crohn’s disease
CDE
Center of Drug Evaluation
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKDEPI
Chronic Kidney Disease Epidemiology Collaboration
CL
clearance
CL/F
apparent clearance
Clast
last quantifiable concentration
Clast*
predicted serum concentration at the last quantifiable time point 
Cmax
maximum observed concentration
Cmax(dn)
dose normalized Cmax
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CT
clinical trial
DCT
data collection tool
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Abbreviation
Term
DILI
drug-induced liver injury
DMC
data monitoring committee
dn
dose normalized to 1 mg
DNA
deoxyribonucleic acid
DR3
Death Receptor 3
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EFD
embryo-fetal development
eGFR
estimated glomerular filtration rate 
EMA
European Medicines Agency
eNCA
electronic non-compartmental analysis
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
F
apparent bioavailability/estimate of bioavailability for the SC doses 
relative to IV dosing
FIH
first in human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GD
Gestation Days
GGT
gamma-glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HBV
hepatitis B
HBVDNA
hepatitis B DNA
HCVAb
hepatitis C antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
investigator’s brochure
IBD
inflammatory bowel disease
ICD
informed consent document
ICH
International Council for Harmonisation
IFN
interferon
IgG
immunoglobulin G
IGRA
Interferon Gamma Release Assay
IL
interleukin
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
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Abbreviation
Term
IRB
institutional review board
IUD
intrauterine device 
IUS
Intrauterine hormone-releasing system 
IV
intravenous
LBBB
left bundle branch block
LFT
liver function test
MAD
multiple ascending doses
MRI
magnetic resonance imaging
msec
millisecond
N/A
not applicable
NAb
neutralizing antibodies
NOAEL
no-observed-adverse-effect level
PC
positive control
PCRU
Pfizer Clinical Research Unit
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PPD
purified protein derivative
PR
pulse rate
PT
prothrombin time
PVC
premature ventricular contraction/complex
QFT-G
QuantiFERON-TB GoldIn-Tube
Q2W
every 2 weeks
Q4W
every 4 weeks
QRS
part of electrocardiographic wave
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac
observed accumulation ratio
Rac, Cmax
observed accumulation ratio for Cmax 
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SCr
serum creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
sTL1A
soluble TL1A
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
Th1
T helper type 1
Th2
T helper type 2
Th9
T helper type 9
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Abbreviation
Term
Th17
T helper type 17
TL1A
tumor necrosis factor like ligand 1A
Tmax
time at which Cmax occurred
TNF
tumor necrosis factor
t½
terminal elimination half life
TBili
total bilirubin
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
Vss
volume of distribution
Vz/F
apparent volume of distribution
WBC
white blood cell
WOCBP
woman of childbearing potential
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11. REFERENCES
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Migone TS, Zhang J, Luo X, et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 
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Prehn JL, Thomas LS, Landers CJ, et al. The T cell costimulator TL1A is induced by 
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4
Shih DQ, Kwan LY, Chavez V, et al. Microbial induction of inflammatory bowel 
disease associated gene TL1A (TNFSF15) in antigen presenting cells. Eur J Immunol 
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5
Papadakis KA, Prehn JL, Landers C, et al. TL1A synergizes with IL-12 and IL-18 to 
enhance IFN-gamma production in human T cells and NK cells. J Immunol 2004; 
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Prehn JL, Mehdizadeh S, Landers CJ, et al. Potential role for TL1A, the new TNF-
family member and potent costimulator of IFN-gamma, in mucosal inflammation. Clin. 
Immunol. 2004; 112(1):66-77.
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Papadakis KA, Zhu D, Prehn JL, et al. Dominant role for TL1A/DR3 pathway in IL-12 
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Pappu BP, Borodovsky A, Zheng TS, et al. TL1A-DR3 interaction regulates Th17 cell 
function and Th17-mediated autoimmune disease. J Exp Med 2008; 205(5):1049-62.
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Takedatsu H, Michelsen KS, Wei B, et al. TL1A (TNFSF15) regulates the development 
of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. 
Gastroenterology 2008; 135(2):552-67.
10
Richard AC, Tan C, Hawley ET, et al. The TNF-family ligand TL1A and its receptor 
DR3 promote T cell-mediated allergic immunopathology by enhancing differentiation 
and pathogenicity of IL-9-producing T cells. J Immunol 2015; 194:3567-82.
11
Holmkvist P, Roepstorff K, Uronen-Hansson H, et al. A major population of mucosal 
memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte 
functionality. Mucosal Immunol 2015; 8(3):545-58.
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12
Meylan F, Hawley ET, Barron L, et al. The TNF-family cytokine TL1A promotes 
allergic immunopathology through group 2 innate lymphoid cells. Mucosal Immunol 
2014; 7(4):958-68.
13
Yu X, Pappu R, Ramirez-Carrozzi V, et al. TNF superfamily member TL1A elicits type 
2 innate lymphoid cells at mucosal barriers. Mucosal Immunol 2014; 7(3):730-40.
14
Meylan F, Davidson TS, Kahle E, et al. The TNF-family receptor DR3 is essential for 
diverse T cell-mediated inflammatory diseases. Immunity 2008; 29(1):79-89.
15
Yamazaki K, McGovern D, Ragoussis J, et al. Single nucleotide polymorphisms in 
TNFSF15 confer susceptibility to Crohn's disease. Hum Mol Genet 2005; 14(22):3499-
506.
16
Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 
30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008; 40(8):955-62.
17
Kakuta Y, Ueki N, Kinouchi Y, et al. TNFSF15 transcripts from risk haplotype for 
Crohn's disease are overexpressed in stimulated T cells. Hum Mol Genet 2009; 
18(6):1089-98.
18
Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the 
genetic architecture of inflammatory bowel disease. Nature 2012; 491(7422):119-24.
19
Yamazaki K, Umeno J, Takahashi A, et al. A genome-wide association study identifies 
2 susceptibility Loci for Crohn's disease in a Japanese population. Gastroenterology 
2013; 144(4):781-8.
20
Bamias G, Martin C, III, Marini M, et al. Expression, localization, and functional 
activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J 
Immunol 2003 November 1;171(9):4868-74.
21
Bamias G, Mishina M, Nyce M, et al. Role of TL1A and its receptor DR3 in two models 
of chronic murine ileitis. Proc Natl Acad Sci USA 2006; 103(22):8441-6.
22
Kamada N, Hisamatsu T, Honda H, et al. TL1A produced by lamina propria 
macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in 
patients with Crohn’s disease. Inflamm Bowel Dis 2010; 16(4):568-75.
23
Meylan F, Richard AC, Siegel RM. TL1A and DR3, a TNF family ligand-receptor pair 
that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune 
inflammation. Immunol Rev 2011; 244(1):188-96.
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24
Taraban VY, Slebioda TJ, Willoughby JE, et al. Sustained TL1A expression modulates 
effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia. 
Mucosal Immunol 2011; 4(2):186-96.
25
Bamias G, Kaltsa G, Siakavellas SI, et al. Differential expression of the TL1A/DcR3 
system of TNF/TNFR-like proteins in large vs. small intestinal Crohn’s disease. Dig 
Liver Dis. 2012 Jan;44(1):30-6.
26
Chiba K, Yoshitsugu H, Kyosaka Y, et al. A comprehensive review of the 
pharmacokinetics of approved therapeutic monoclonal antibodies in Japan: Are Japanese 
phase I studies still needed? J Clin Pharmacol 2014;54(5):483-94.
27
Banholzer ML, Wandel C, Barrow P, et al. Clinical trial considerations on male 
contraception and collection of pregnancy information from female partner: update. Clin 
Transl Med 2016;5(1):23 37.
28
Levey AS, Stevens LA, Schmid CH, et al. CKD-EPI (Chronic Kidney Disease 
Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann 
Intern Med. 2009;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006. 
Erratum in: Ann Intern Med. 2011 Sep 20;155(6):408. PMID: 19414839; PMCID: 
PMC2763564.
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SAP_001.pdf: 
Protocol B7541013 (PF-06480605) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 1
Protocol B7541013
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO 
CONTROLLED STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY 
AND TOLERABILITY FOLLOWING SINGLE SUBCUTANEOUS DOSE OF 
PF-06480605 IN CHINESE HEALTHY PARTICIPANTS
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
25 Apr 2022
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................3
APPENDICES ...........................................................................................................................3
1. VERSION HISTORY............................................................................................................4
2. INTRODUCTION .................................................................................................................5
2.1. Study Objectives, Endpoints, and Estimands............................................................5
2.2. Study Design .............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7
3.1. Primary Endpoint(s) ..................................................................................................7
3.2. Secondary Endpoint(s) ..............................................................................................7
3.3. Other Endpoint(s)......................................................................................................7
3.4. Baseline Variables.....................................................................................................7
3.5. Safety Endpoints .......................................................................................................7
3.5.1. Adverse Events.............................................................................................7
3.5.2. Vital Signs ....................................................................................................7
3.5.3. Electrocardiograms.......................................................................................8
3.5.4. Physical Examination ...................................................................................8
3.5.5. Laboratory Data............................................................................................8
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS).....................................................9
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................10
5.1. Hypotheses and Decision Rules ..............................................................................10
5.2. General Methods .....................................................................................................10
5.2.1. Analyses for Binary Endpoints...................................................................10
5.2.2. Analyses for Continuous Endpoints ...........................................................10
5.2.3. Analyses for Categorical Endpoints ...........................................................10
5.3. Methods to Manage Missing Data ..........................................................................10
5.3.1. Concentrations Below the Limit of Quantification ....................................10
5.3.2. Deviations, Missing Concentrations and Anomalous Values.....................10
5.3.3. PK Parameters ............................................................................................11
6. ANALYSES AND SUMMARIES ......................................................................................11
6.1. Primary Endpoint(s) ................................................................................................11
6.1.1. Primary PK Parameters...............................................................................11
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6.1.2. Adverse Events...........................................................................................12
6.1.3. Vital Signs ..................................................................................................12
6.1.4. Electrocardiograms.....................................................................................13
6.1.5. Physical Examination .................................................................................13
6.1.6. Laboratory Data..........................................................................................13
6.2. Secondary Endpoint(s) ............................................................................................13
6.2.1. Secondary PK Parameters...........................................................................13
6.2.2. Immunogenicity Endpoints.........................................................................14
6.2.3. PD Biomarker.............................................................................................14
6.3. Subset Analyses.......................................................................................................15
6.4. Baseline and Other Summaries and Analyses.........................................................15
6.4.1. Baseline Summaries....................................................................................15
6.4.2. Study Conduct and Participant Disposition................................................15
6.4.3. Concomitant Medications and Nondrug Treatments..................................15
6.5. Safety Summaries and Analyses .............................................................................15
7. INTERIM ANALYSES.......................................................................................................16
8. REFERENCES ....................................................................................................................16
9. APPENDICES .....................................................................................................................17
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................4
Table 2.
Randomization Scheme ..............................................................................6
APPENDICES
Appendix 1. List of Abbreviations...........................................................................................18
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1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated
Protocol 
Amendment
Rationale
Specific Changes
1/
08 Feb 2021
Original 
29 Dec 2020
N/A
N/A
2/
25 Apr 2022
Original
29 Dec 2020
To respond to 
the additional 
comments
•
Section 3.4: changed the wording for the 
baseline to be more precise.
•
Section 3.5.1: changed the wording for 
the definition of TEAE to be consistent 
with the algorithm of TEAE defined in 
the newest version of CaPS.
•
Sections 3.5.2, 3.5.3: removed the hours 
of collection days to be flexible in the 
analyses.
•
Section 3.5.5: removed the hours of 
collection days to be flexible in the 
analyses, and added “The full list of …” 
in the end of second paragraph for 
clarification.
•
Section 4: added content and modified 
the format of table to be consistent with 
the newest SAP template.
•
Section 5.2: removed “or summaries”.
•
Section 6.1.2: added injection site 
reactions to the endpoint of AEs.
•
Section 6.2.1: removed “AUC14days(dn)” 
and added content for completeness of 
section.
•
Section 6.3: removed this section and 
re-number the subsequent sections.
•
Section 6.4.1: added more demographic 
examples.
•
Section 6.4.2: removed “for safety”.
•
Section 6.5: added COVID-19 related 
safety analyses
•
Section 9, Appendix 1: added and 
removed abbreviations to adjust to the 
content of SAP.
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2. INTRODUCTION
PF-06480605 is a fully human IgG1 monoclonal antibody against Tumor Necrosis Factor 
like Ligand 1A (TL1A), a member of the tumor necrosis factor (TNF) family of cytokines, that 
is currently in development for the treatment of Crohn’s disease (CD) and ulcerative colitis 
(UC). The mechanism of action of PF-06480605 is to neutralize the binding and subsequent 
signaling of TL1A to its functional receptor Death Receptor 3 (DR3) on immune cells of the 
innate and adaptive immune system.
The purpose of the study is to evaluate the PK, safety, tolerability, immunogenicity, and PD 
of PF-06480605 in Chinese healthy adult participants. The information of the PK, safety, 
tolerability, immunogenicity, and PD in Chinese healthy participants is being collected to 
support further clinical development as well as drug registration in China.
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study B7541013. 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, Endpoints, and Estimands
Estimands are not applicable to this Phase 1 study.
Objectives
Endpoints
Primary: 
Primary: 
•
To characterize the PK of PF-06480605 
following administration of single SC dose of 
PF-06480605 450 mg and 150 mg (if needed) 
in Chinese healthy adult participants.
•
To evaluate the safety and tolerability 
following administration of single SC dose of 
PF-06480605 450 and 150 mg (if needed) in 
Chinese healthy adult participants.
•
Serum PF-06480605 primary PK parameters, as 
permitted by data: Cmax, Tmax, AUC14 days, 
AUCinf, and t½.
•
Assessment of AEs, vital signs, 12-lead 
electrocardiograms, physical examination 
findings and clinical safety laboratory 
measurements.
Secondary: 
Secondary: 
•
To further evaluate the PK of PF-06480605.
•
To evaluate the immunogenicity of 
PF-06480605.
•
To evaluate the PD biomarker (if feasible) 
which may be informative in demonstrating 
the pharmacologic effect of PF-06480605.
•
Serum PF-06480605 PK parameters, as 
permitted by data: AUClast, Cmax(dn), 
AUCinf(dn), and AUClast(dn), Vz/F and CL/F.
•
Incidence of the development of ADA and NAb.
•
Total sTL1A protein concentration in serum.
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2.2. Study Design
This is a Phase 1, single-center, randomized, double-blind, third-party open (participant 
blind, investigator blind, sponsor open), placebo -controlled study to investigate PK, safety, 
tolerability, immunogenicity, and PD of PF-06480605 following a single subcutaneous dose 
of PF-06480605 450 mg and 150 mg (if needed) in Chinese healthy adult participants. 
Optional 150 mg cohort will be conducted only if data from 450 mg cohort does not confirm 
expected PK based on previous studies in healthy Western and Japanese participants as well 
as UC patients.
A maximum of approximately 24 participants (18 with active treatment and 6 with placebo) 
will be randomized and receive the investigational product such that approximately 12 
participants are assigned to each cohort (450 mg and 150 mg) to ensure that 11 evaluable 
participants per cohort will complete the study. Participants will be enrolled to both cohorts 
sequentially, starting with the 450 mg cohort first. When the 150 mg cohort is determined to 
be needed, the 150 mg cohort with entirely new participants will be opened.
The 150 mg cohort will be started only if it indicates the ethnic PK difference (eg, more than 
two-fold higher exposure) based on all available serum concentrations data of PF-06480605 
obtained until the timing when the PK sample is collected at Day 14 after administration, by 
comparing the dose-normalized mean exposures (or dose-normalized mean concentrations 
profiles) in this study versus dose-normalized mean exposures in Western study B7541001 
and Japanese study B7541006. 
Table 2.
Randomization Scheme
Cohort
Treatment
Number of participants
1
PF-06480605 450 mg
9
Placebo
3
2 (optional)
PF-06480605 150 mg
9
Placebo
3
Participants, who drop out from the study if the number of participants completing at least 
the follow-up visit at Day 57 per cohort decreases to 10 or lower, will be replaced.
If a participant discontinues before completing the part of the study to which they have been 
randomized, or withdraws for reasons unrelated to the safety of the investigational product, 
the participant may be replaced at the discretion of the investigator upon consultation with 
the sponsor.
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single dose of PF-06480605 450 mg or 150 mg (if 
needed) or placebo. Participants will be admitted into the CRU approximately 1 day prior to 
dosing and required to stay overnight in the CRU at least through completion of the Day 5 
evaluations. Participants will return for outpatient follow-up visits through Day 114.
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3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
The primary endpoints consist of PK and safety endpoints.
•
Serum PF-06480605 primary PK parameters, as permitted by data: Cmax, Tmax, 
AUC14 days, AUCinf, and t½.
•
Assessment of AEs, vital signs, 12 lead electrocardiograms, physical examination 
findings and clinical safety laboratory measurements.
3.2. Secondary Endpoint(s)
The secondary endpoints are additional PK, immunogenicity and PD biomarker endpoints
defined as follows.
•
Serum PF-06480605 PK parameters, as permitted by data: AUClast, Cmax(dn), 
AUCinf(dn), and AUClast(dn), Vz/F and CL/F.
•
Incidence of the development of ADA and Nab.
•
Total sTL1A protein concentration in serum.
3.3. Other Endpoint(s)
There are no other endpoints defined in this study.
3.4. Baseline Variables
Baseline value is defined as the latest value before receiving the dose of study intervention.
3.5. Safety Endpoints
3.5.1. Adverse Events
An adverse event is considered treatment emergent if the event starts during the effective 
study period (CRU confinement and follow-up visits).
All events that start on or after the dosing day and time, if collected, but before the end of 
study will be flagged as TEAEs. The algorithm will not consider any events that started prior 
to the dose date. If an AE starts on the same day as the dose date, it will be considered 
treatment emergent unless the CRF data indicates otherwise via explicitly recording time for 
AE onset and treatment dosing.
3.5.2. Vital Signs
Supine BP, PR measurements and axillary temperature are collected during the CRU 
confinement on Day 1 and Day 5, and during the follow-up visits on Day 10 and Day 
114/ET.
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3.5.3. Electrocardiograms
Single 12-Lead ECGs are collected during the CRU confinement on Day 1 and Day 5, and 
during the follow-up visits on Day 10 and Day 114/ET. Repeat ECGs may be taken 
following the study protocol at each assessment time.
Changes from baseline for the ECG parameters: QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
3.5.4. Physical Examination
Height and body weight are only collected at screening. A full physical examination may be 
done at screening or Day -1. Brief physical examination to follow up open AEs after Day -1 
may be done.
3.5.5. Laboratory Data
The safety laboratory tests of hematology, chemistry and urinalysis are performed during the 
screening, the CRU confinement on days: -1, 2 and 5, and the follow-up visits on days: 10, 
15, 57, 85 and 114/ET.
Additional laboratory results may be reported on these samples as a result of the method of 
analysis or the type of analyzer used by the clinical laboratory, or as derived from calculated 
values. These additional tests would not require additional collection of blood. The full list of 
laboratory tests/assessments is shown in Table 4 in the protocol.
Hematology
Chemistry
Urinalysis
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
Additional Tests (Needed for 
Hy’s Law)
AST, ALT (repeat)
Total bilirubin (repeat)
Albumin (repeat)
Alkaline phosphatase 
(repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
GGT
PT/INR
a.
Only if urine dipstick is positive for blood, or leukocyte esterase.
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To determine if there are any abnormalities of potential clinical concern, the hematology, 
chemistry and urinalysis safety tests will be assessed against the criteria specified in the 
CDISC and Pfizer standards (CaPS). The assessment will take into account whether each 
participant’s baseline test result is within or outside the laboratory reference range for the 
particular laboratory parameter.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis set prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
For purposes of PK/PD, safety and immunogenicity analyses, the following analysis sets are 
defined:
Population
Description
Applicable Analysis (for 
additional information  
refer to section 6)
Safety 
All randomized participants who applied at 
least 1 dose of study intervention.
Analysis for safety 
endpoints
PK 
Concentration 
All randomized participants who applied at 
least 1 dose of study intervention and for 
whom at least 1 concentration value is 
reported.
Analysis for PK 
concentration
PK Parameter 
All randomized participants who applied at 
least 1 dose of
study intervention and for whom at least 1 
of the PK
parameters of interest (e.g., AUCinf and 
Cmax) is calculated.
Analysis for PK 
parameters
Immunogenicity
All randomized participants who applied at 
least 1 dose of study intervention with at 
least 1 post-treatment anti-drug 
(PF-06480605) antibody determination.
Analysis for 
immunogenicity
endpoints
PD
All randomized participants who have at 
least 1 PD assessment.
Analysis for PD 
biomarkers
All analyses will not include data from participants who are randomized but not treated. If a 
participant receives a treatment that is not consistent with the treatment they were randomly 
assigned to, then the participant will be reported under the treatment that the participant 
actually received for all PK/PD, safety and immunogenicity analyses, where applicable.
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5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
No formal statistical hypothesis testing will be conducted the analyses in this study.
5.2. General Methods
No formal statistical tests will be performed. Descriptive analyses will be provided for all 
endpoints by treatment for each cohort.
Additionally, a population PK model will be developed to characterize the PK and assess the 
effect of ethnicity on PK using all available data. The detailed analysis plans will be 
described in a separate pharmacometric analysis plan.
5.2.1. Analyses for Binary Endpoints
Number and percentage of participants in each category will be used to summarize the 
endpoints, if not otherwise specified.
5.2.2. Analyses for Continuous Endpoints
The summary statistics n, arithmetic mean, median, standard deviation (SD), minimum and 
maximum will be used to summarize the endpoints, if not otherwise specified.
The summary statistics for PK parameters are described in Section 6.2.
5.2.3. Analyses for Categorical Endpoints
Number and percentage of participants in each category will be used to summarize the 
endpoints, if not otherwise specified.
5.3. Methods to Manage Missing Data
Missing data will not be imputed.
5.3.1. Concentrations Below the Limit of Quantification
In all data presentations (except listings), PK and PD concentrations below the limit of 
quantification (BLQ) will be set to zero. In listings, BLQ values will be reported as “<LLQ”, 
where LLQ will be replaced with the value for the lower limit of quantification.
5.3.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables, plots of mean profiles and plots of median profiles, summary statistics
will be calculated by setting concentrations to missing if one of the following cases is true:
•
A concentration has been collected as ND (Not Done) or NS (No Sample).
•
A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50%
of the data are missing.
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5.3.3. PK Parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a participant’s concentration data, the parameter
will be coded as NC (Not Calculated). Note that NC values will not be generated beyond the 
day a participant discontinues.
In summary tables, summary statistics will be calculated by setting NC values to missing;
and summary statistics will not be presented at a particular time point if more than 50% of
the data are missing.
If an individual participant has a known biased estimate of a PK parameter (eg, due to known
loss of drug during SC administration), this will be footnoted in summary tables and will not
be included in the calculation of summary statistics.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
The primary endpoints include PK and safety endpoints.
The primary PK parameters will be calculated from the concentration-time values for each 
participant, as applicable, using noncompartmental analysis as described in the protocol. The 
primary PK parameters will be listed and summarized for participants in the PK parameter 
analysis set. Each PK parameter will be summarized by dose (450 mg, 150 mg [if needed]) 
and will include the set of summary statistics as specified in the table in Section 6.1.1.
The safety endpoints will be listed and summarized by treatment (450 mg, 150 mg [if 
needed] and placebo) for participants in the safety analysis set. All participants received 
placebo in either 450 mg or 150 mg (if needed) cohort will have a pooled placebo group.
6.1.1. Primary PK Parameters
Parameter
Summary statistics
Cmax, AUC14 days, AUCinf
n, arithmetic mean, median, SD, minimum,
maximum, percent coefficient of variation (%CV), 
geometric mean and geometric %CV.
Tmax
n, median, minimum, maximum.
t½
n, arithmetic mean, median, SD, minimum, 
maximum, %CV.
There will be one summary table presenting all PK parameters for each dose (450 mg and 
150 mg [if needed]). The PK concentrations will be listed and summarized for participants in 
the PK concentration analysis set. Presentations for PF-06480605 concentrations will 
include:
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•
A listing of all concentrations sorted by subject ID, dose and nominal time postdose.
The concentration listing will also include the actual times. Deviations from the
nominal time will be given in a separate listing.
•
A summary of concentrations by dose and nominal time postdose, where the set of 
summary statistics will include n, arithmetic mean, median, SD, %CV, minimum, 
maximum and the number of concentrations above the lower limit of quantification.
•
Individual concentration time plots by dose (on both linear and semi-log scales) 
against actual time postdose (there will be separate spaghetti plots for each dose per 
scale).
•
Individual concentration time plots by participant (on both linear and semi-log scales) 
against actual time postdose (there will be separate plots for each participant per 
scale).
•
Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose (all doses on the same plot per scale, based on the summary of 
concentrations by dose and time postdose).
•
Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose (all doses on the same plot per scale, based on the summary of 
concentrations by dose and time postdose).
Note that if the cohort of 150 mg is not needed, then all the presentations above will only be 
available for 450 mg. The length of time used for the ݔ-axes of these plots will be decided on 
review of the data, and will depend on how long PF-06480605 concentration is quantifiable 
in the matrix.
For summary statistics, mean and median plots by sampling time, the nominal PK sampling 
time will be used. For individual participant plots by time, the actual PK sampling time will 
be used.
6.1.2. Adverse Events
AEs (including injection site reactions) will be listed and summarized following CaPS.
6.1.3. Vital Signs
Absolute values and changes from baseline on vital signs will be listed and summarized by 
treatment following CaPS. In addition, the maximum increase and decrease from baseline 
over all measurements taken postdose for supine systolic blood pressure (BP) and diastolic 
BP will also be determined.
The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each postdose measurement to give the change from baseline. The maximum of 
these values over all measurements will then be selected, except for cases in which a 
participant does not show an increase. In such an instance, the minimum decrease should be 
taken.
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Similarly, the maximum decrease from baseline will be determined by selecting the 
minimum value of the changes from baseline. In cases where a participant does not show a 
decrease, the minimum increase should be taken.
6.1.4. Electrocardiograms
A listing of all ECG data sorted by subject ID, treatment and nominal time postdose will be 
produced. 
Absolute values and changes from baseline for the ECG parameters (ie, QT interval, QTc 
interval, PR interval, and QRS interval) will be summarized by treatment and time postdose 
following CaPS. Average values of the ECG parameters for a participant will be calculated 
for summarization when ECG repeated at any assessment time for the participant. 
The number and percentage of participants with maximum postdose QTc values and 
maximum increase from baseline in the following categories will be tabulated by treatment:
Safety QTc Assessment
Degree of 
Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450 – 480
>480 – 500
>500
Increase from baseline
30 – 60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
6.1.5. Physical Examination
Absolute values of height and body weight at baseline will be listed and summarized by 
treatment following CaPS.
6.1.6. Laboratory Data
Absolute values and changes from baseline on laboratory data will be listed and summarized 
by treatment following CaPS.
6.2. Secondary Endpoint(s)
The secondary endpoints are additional PK, immunogenicity and PD biomarker endpoints.
6.2.1. Secondary PK Parameters
Each PK parameter will be summarized as described in Section 6.1.1 and will include the set 
of summary statistics as specified in the table below:
Parameter
Summary statistics
Cmax(dn), AUClast, AUCinf(dn), AUClast(dn), Vz/F, 
CL/F
n, arithmetic mean, median, SD, minimum,
maximum, %CV, geometric mean and geometric 
%CV.
dn = dose normalized to 1 mg
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To assess the relationship between the PK parameters and dose, dose normalized parameters 
Cmax(dn), AUClast(dn) and AUCinf(dn) (if data permitted) will be plotted against dose (using a 
logarithmic scale) and will include individual participants values and the geometric means 
for each dose. Geometric means will have a different symbol than the individual values. The 
values will be dose normalized to 1 mg by dividing the individual values and raw geometric 
means by dose. A footnote will be added to the plots to indicate that geometric means are 
presented. Note that if the cohort of 150 mg is needed, then the dose will include both 450 
mg and 150 mg and perform a within-study comparison; if the cohort of 150 mg is not 
needed, then the analyses will only be based on dose of 450 mg and no within-study 
comparison will be performed.
6.2.2. Immunogenicity Endpoints
The incidence of the development of ADA and NAb will be listed and summarized for 
participants in the immunogenicity analysis set. Presentations for PF-06480605 
concentrations will include:
•
Listing of ADA and NAb incidence sorted by subject ID and dose.
•
Summary of ADA and NAb incidence by dose and time.
•
Summary of ADA and NAb incidence by overall postdose measurements (if 150 mg 
is conducted).
•
Summary of treatment emergent ADA and NAb positive participants. An ADA 
incidence is considered treatment emergent if any ADA positive occurs for the first
time after dosing and was negative at Day 1 (0 hr predose). An NAb incidence is
considered treatment emergent if any NAb positive occurs for the first time after
dosing and was negative at Day 1 (0 hr predose).
•
Summary of mean PK concentrations by ADA and NAb status, dose and time 
postdose.
•
Summary of mean PK parameters by ADA and NAb status and dose.
Immunogenicity assay titers will be used to determine incidence for ADA and NAb. Titer 
values will also be listed.
6.2.3. PD Biomarker
The PD biomarker endpoints will be listed and summarized for participants in the PD 
analysis set. Presentations for total sTL1A protein concentration in serum will include:
•
A listing of sTL1A observed value, change and percent change from baseline sorted 
by subject ID and treatment (450 mg, 150 mg [if needed] and placebo). The sTL1A 
listing will also include the actual test times.
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•
A summary of sTL1A observed value, change and percent change from baseline 
sorted by time postdose and treatment, where the set of summary statistics will 
include n, arithmetic mean, SD, median, 25% quantile and 75% quantile.
•
Individual plots of sTL1A against actual time postdose (there will be separate plots 
for each dose per scale).
•
Individual plots of change from baseline in sTL1A against actual time postdose (there 
will be separate plots for each dose per scale).
•
Individual plots of percent change from baseline in sTL1A against actual time 
postdose (there will be separate plots for each dose per scale).
•
Mean sTL1A time plots against nominal time postdose (all treatments on the same 
plot per scale, based on the summary of concentrations by treatment and time 
postdose).
•
Median sTL1A time plots against nominal time postdose (all treatments on the same 
plot per scale, based on the summary of concentrations by treatment and time 
postdose).
6.3. Subset Analyses
No formal subset analysis will be conducted for this study.
6.4. Baseline and Other Summaries and Analyses
6.4.1. Baseline Summaries
Demographic data (age, sex, ethnicity and race etc.) will be summarized following CaPS.
6.4.2. Study Conduct and Participant Disposition
The following participant dispositions will be summarized.
•
A summary of participant discontinuations up to end of study;
•
Summary of participant disposition;
•
Summary of numbers of participant treated by treatment group.
Data will be reported following CaPS.
6.4.3. Concomitant Medications and Nondrug Treatments
All concomitant medications as well as nondrug treatments will be summarized following 
CaPS.
6.5. Safety Summaries and Analyses
In order to report the impact of COVID-19 on clinical trial populations and study data, the 
following additional listings and summaries will be produced:
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•
Listing of participants affected by COVID-19 related study disruption;
•
Protocol deviations related to COVID-19;
•
Discontinuations from study drug due to COVID-19 related AEs.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor may conduct unblinded reviews of the data of 450 mg SC cohort through Day 14 
and during the course of the study for the purpose of determining whether or not to conduct 
150 mg SC cohort, and preliminarily assess any ethnic differences between Chinese and non-
Chinese, thus to support China joining further global Phase 2 or Phase 3 studies.
The 150 mg cohort will be started only if it indicates the ethnic PK difference (eg, more than 
two-fold higher exposure) based on all available serum concentrations data of PF-06480605 
obtained until the timing when the PK sample is collected at Day 14 after administration, by 
comparing the dose-normalized mean exposures (or dose-normalized mean concentrations 
profiles) in this study versus dose-normalized mean exposures in Western study B7541001 
and Japanese study B7541006.
8. REFERENCES
Not applicable.
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9. APPENDICES
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Appendix 1. List of Abbreviations
Abbreviation
Term
AE
adverse event
AUC
area under the curve
BLQ
below the limit of quantitation
BP
blood pressure
CaPS
CDISC & Pfizer Standards
CD
Crohn’s disease
CDARS
Clinical Data Analysis and Reporting System (of US Food and Drug Administration)
CDISC
Clinical Data Interchange Standard Consortium
Cmax
maximum observed concentration
CRF
case report form
CRU
Clinical research unit
CSR
clinical study report
DMC
data monitoring committee
DR3
Death Receptor 3
EAC
event adjudication committee
ECG
electrocardiogram
E-DMC
external data monitoring committee 
ET
Early termination
FDA
Food and Drug Administration (United States)
GCP
Good Clinical Practice
ICD
informed consent document
ICH
International Council for Harmonisation
IgG
immunoglobulin G
IRC
internal review committee
LLOQ
lower limit of quantitation
LOD
limit of detection
MedDRA
Medical Dictionary for Regulatory Activities
N/A
not applicable
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Abbreviation
Term
NC
Not Calculated
ND
Not Done
NS
No Sample
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PRO
patient-reported outcome
PR
Pulse rate
PT
preferred term
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
RCDC
reverse cumulative distribution curve
RR
relative risk
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SD
standard deviation
SGS
Statistical Guidance Standards
SOP
standard operating procedure
TA
therapeutic area
TL1A
Tumor Necrosis Factor like Ligand 1A
TNF
tumor necrosis factor
UC
ulcerative colitis
ULN
upper limit of normal
%CV
percent coefficient of variation
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