A PHASE 1, SINGLE-ARM, OPEN-LABEL, NON-RANDOMIZED, NON-CONTROLLED MULTICENTER STUDY TO EVALUATE THE PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND TOLERABILITY OF A SINGLE SUBCUTANEOUS DOSE OF PF-06741086 IN CHINESE ADULT PARTICIPANTS WITH SEVERE HEMOPHILIA
Phase: PHASE1
Conditions: Severe Hemophilia
Sponsor: Pfizer

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A PHASE 1, SINGLE-ARM, OPEN-LABEL, NON-RANDOMIZED, NON-
CONTROLLED MULTICENTER STUDY TO EVALUATE THE 
PHARMACOKINETICS, PHARMACODYNAMICS, SAFETY, AND 
TOLERABILITY OF A SINGLE SUBCUTANEOUS DOSE OF PF-06741086 IN 
CHINESE ADULT PARTICIPANTS WITH SEVERE HEMOPHILIA
Investigational Product Number:
PF-06741086
Investigational Product Name:
Marstacimab
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2018-003660-31
Protocol Number:
B7841010
Phase:
1
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information 
in confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
CCI

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procedures should proceed to completion.  
If a participant experiences a bleeding 
episode after Day 28 following the initial 
administration of PF-06741086, the 
participant is to be stabilized utilizing the 
participant’s usual hemostatic treatment 
regimen.
7.1 Discontinuation of 
Study Intervention
Revised: Since this is a single-dose study, 
this section is not applicable. In rare 
instances, it may be necessary for a 
participant to permanently discontinue 
investigational product.  If investigational 
product is permanently discontinued, the 
participant will withdraw from the study.
If a clinically significant
finding is 
identified pre dosing, the investigator or 
qualified designee will determine if the 
participant can continue in the study and if 
any change in participant management is 
needed. Any new clinically relevant finding 
should be reported as an AE.
See the SoA for data to be collected at the 
time of intervention discontinuation and 
follow up and for any further evaluations 
that need to be completed
Revised according to the 
appropriate protocol template.
7.2 Participant 
Discontinuation/Withdraw
al From the Study
Revised: A participant may withdraw from 
the study at any time at his own request. 
Reasons for discontinuation from the study 
include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

or may be withdrawn at any time 
at the discretion of the 
investigator for safety, behavioral,
compliance, or administrative 
reasons.
To comply with the updated 
protocol template.
7.2 Participant 
Discontinuation/Withdraw
al From the Study
Revised: See the SoA (visit Day 7) for 
assessments
Added missed assessment for 
discontinuation in SoA.
7.2 Participant 
Discontinuation/Withdraw
al From the Study
Revised: If a participant withdraws from 
the study, he may request destruction of 
any remaining samples taken and not 
tested, but data already generated from the 
samples will continue to be available, and 
may be used to protect the integrity of 
existing analyses. 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 below
Revised based on the new 
protocol template.

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Section 7.2.1) for disclosure of future 
information
Section 8
Table 3 Blood Volume
Updated sample volume in Table 3
Updated sample volume to 
reflect central &local laboratory 
specifications for sample 
analyses
Section 8
Added: 8.1. Efficacy Assessments
Not applicable.
Mandatory section in new 
protocol template
8.2.3 Electrocardiograms
Revised: At each time point at which 
triplicate ECG are required (ie, when 
single ECG is abnormal or when troponin I 
is abnormal), 3 individual ECG tracings 
should be obtained abnormal or when 
troponin I is abnormal)
Deleted the repeated content
8.2.3 Electrocardiograms
Changed “Appendix 7” to “Appendix 6”
8.2.3 Electrocardiograms
Revised: the triplicate ECG measurements 
collected at each nominal time point 
during Observational Phase Visit at pre-
dose Day1 will serve as each participant’s 
baseline value.
Correction of error.
8.2.5 Injection Site 
Reaction
Deleted: Participants will be provided  
written instructions and will be trained by 
study staff on the ment of injection site 
reactions.
Deleted inappropriate content.
8.3.1 Time Period and 
Frequency for Collecting 
AE and SAE Information
Revised: 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 case 
report form (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 AEs or SAEs after conclusion of the 
study participation.
However, if the 
To comply with the updated 
protocol template.

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investigator learns of any SAE, including a 
death, at any time after a participant has 
been discharged from the study, and he/she 
considers the event to be reasonably related 
to the study intervention, the investigator 
must promptly report the SAE to Pfizer 
using the CT SAE Report Form.
8.3.1.2 Recording 
Nonserious AEs and SAEs 
on the CRF
Revised: All nonserious AEs and SAEs 
occurring in a participant during the active 
collection period, which begins after 
obtaining informed consent as described in 
Section 8.2.1, will be recorded on the AE 
section of the CRF.
The investigator is to record on the CRF 
all directly observed and all spontaneously 
reported AEs and SAEs reported by the 
participant.
During the active collection period, both 
nonserious AEs and SAEs are recorded on 
the CRF.
To comply with the updated 
protocol template.
Section 8.3
Added: 8.3.8. Adverse Events of Special 
Interest
Not applicable.
To comply with the updated 
protocol template.
Throughout section 8.3.9
Medical Device 
Deficiencies
Changed “device incidents or 
malfunctions” to “device deficiencies”
Changed “device incident” to “device 
deficiency”
Changed “Appendix 8” to “Appendix 7”
To comply with the updated 
protocol template.
8.3.9.2 Follow-up of 
Medical Device 
Deficiencies
Follow-up applies to all participants, 
including those who discontinue study 
intervention.
All medical device incidents involving an 
AE will be followed and reported in the 
same manner as other AEs (see Section 
8.2.3).  This applies to all participants, 
including those who discontinue study 
intervention.
To comply with the updated 
protocol template.
8.3.9.3 Prompt Reporting 
of Device Deficiencies to 
Sponsor
Device deficiencies incidents will be 
reported to the sponsor within 24 hours 1 
day after the investigator determines that 
the event meets the protocol definition of a 
medical device incident deficiency. 
Information will be provided to the 
sponsor as described in the IP Manual. 
Any device deficiency that is associated 
with an SAE must be reported to Pfizer 
Safety within 24 hours upon the 
investigator’s awareness as outlined in 
Section 8.3.1.1 and 8.3.1.2
To comply with the updated 
protocol template.
8.4 Treatment of Overdose
Revised: 2. Closely monitor the participant 
for any AEs/SAEs and laboratory 
abnormalities until PF 06741086 can no 
longer be detected systemically (at least 21 
days) for at least 5 half-lives or 28 
Revised according to treatment 
over dose in global Phase 3 
protocol amendment 4 and to 
comply with the updated 

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calendar days after the overdose of study 
intervention (whichever is longer)
3. Obtain 2 blood samples (7 days apart)
for pharmacokinetic (PK) analysis within 7
28 days from the date of the last dose of 
study intervention
protocol template.
Section 8.5.2 
Analysis of Anti-PF-06741086 Antibodies 
and Neutralizing Antibodies to Anti PF-
06741086 Antibodies
Blood samples of approximately 4.5
9.0 mL, to provide approximately 2 3.0 
mL plasma, will be collected for 
determination of anti-PF-06741086 
antibodies (ADA) and neutralizing 
antibodies (NAb) to anti PF-06741086
antibodies.
Each plasma sample will be divided into 2 
aliquots (1 for ADA, 1 for NAb).
Revised for accuracy and 
updated sample volume to 
comply with central lab 
requirement.
8.6 Pharmacodynamic
Revised: Biomarker concentration data 
(TFPI [total and free], Thrombin 
generation, PF1+2, D-dimer, and dPT)  
Revised for accuracy
8.6.1 Tissue Factor 
Pathway Inhibitor
Revised: Blood samples of approximately 
2.7 mL (combined for both total and free 
TFPI), at each timepoint, to provide 
approximately 1.4 mL plasma, will be 
collected into appropriately labeled tubes 
containing sodium citrate for TFPI (total 
and free) analysis as specified in the SoA.
Revised for accuracy
Section 8.6.2
Thrombin Generation Assay
Revised for accuracy
Section 8.6.3
Prothrombin Fragment 1 and 2 (PF1+2)
and Dilute Prothrombin Time (dPT)
Blood samples of approximately 4.5 mL 
(combined for PF1+2 and dPT) will be 
collected into appropriately labeled tubes 
containing sodium citrate to provide 2 
aliquots of 500 µL approximately 1.0 mL 
plasma for PF1+2 analysis and 
approximately 1.0 mL plasma for dPT 
analysis, each (1 for routine testing, 1 
as back up) for PF1+2 and dPT 
analyses, and 2 aliquots of 
approximately 400 µL plasma each 
(1 for routine testing, 1 as back up) 
for coagulation tests analysis of 
D dimer as specified in the SoA
Revised for accuracy
Section 8.6.4
Moved down: D-dimer
Blood samples of approximately 1.8 mL 
will be collected into appropriately labeled 
tubes containing sodium citrate to provide 
approximately 900 µL plasma for D-dimer 
analysis as specified in the SoA. 
Instructions for the collection and handling 
Separated D-dimer as a new 
section for accuracy

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of biological samples will be provided in 
the lab manual or by the sponsor. The 
actual date and time (24-hour clock time) 
of each sample will be recorded.
8.7.1 Specified Genetics
Revised: Genetics (specified analyses) are 
not evaluated in this study. A 5mL blood 
sample for DNA isolation will be collected. 
DNA samples will be analyzed for the 
purpose of assessing Factor V Leiden 
mutation and prothrombin 20210 mutation 
only
at screening. No other genetic 
assessments are conducted.
Corrected genetics testing 
content.
9.3 Populations for 
Analysis
Added population description table
Updated according to new 
protocol template
9.5.1 Electrocardiogram 
Analyses
Added section 9.5.1
To comply with new protocol 
template
10.2 Appendix 2 Table 6
Added “Microscopy 
&
Culturea” in 
urinalysis column
Added “urine drug screeningd” in Other 
column
Added “Total bile acids” in Hy’s law 
column
Revised “a. Only if urinalysis is positive for 
blood, protein, leukocyte or nitrites” in foot 
note
Added “d. At Screening and Day -1 only. 
Minimum requirement for drug screening 
includes:cocaine, 
tetrahydrocannabinol(THC), 
opiates/opioids,benzodiazepines 
and 
amphetamines.” in foot note. 
Revised for accuracy.
10.3 Appendix 3
Added in “Events Meeting the AE 
Definition” :
•
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.
To comply with new protocol 
template.
10.3.2. Definition of SA
Added in the table: f. Other situations:
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 
To comply with new protocol 
template.

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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 
SAE
Changed “none” to “All AEs/SAEs 
associated with exposure during pregnancy 
or breastfeeding.Occupational exposure is 
not recorded” in column of “Recorded on 
the CRF”
Added “Note:  Include all SAEs 
associated with exposure during pregnancy 
or breastfeeding. Include all AEs/SAEs 
associated with occupational exposure.” in 
column of “Reported on the CT SAE 
Report Form to Pfizer Safety Within 24 
Hours of Awareness”
To comply with new protocol 
template.
10.5. 
Added Section Appendix 5: Genetics
To comply with new protocol 
template.
10.6 Appendix 6: Liver 
Safety
In addition to repeating measurements of 
AST and ALT and Tbili for suspected cases 
of Hy’s law, additional laboratory tests 
should include albumin, creatine kinase 
(CK), 
direct 
and 
indirect 
bilirubin, 
gammaglutamyl 
transferase 
(GGT), 
prothrombin 
time 
(PT)/international 
normalized ratio (INR), total bile acids, and 
alkaline phosphatase at the discretion of the 
investigator.
Revised for accuracy
10.8 Appendix 8
Updated the whole section
“Medical 
Device Adverse Events, Adverse Device 
Effects, Serious Adverse Events, and 
Device 
Deficiencies: 
Definition 
and 
Procedures for Recording, Evaluating, 
Follow-up, and Reporting” 
To comply with new protocol 
template.
10.10 Appendix 10: 
Alternative Measures 
During Public 
Emergencies
Added new appendix
New appendix was added 
describing alternative study 
procedures during COVID-19 
pandemic. 

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6.2. Preparation/Handling/Storage/Accountability ........................................................43
6.2.1. Preparation and Dispensing........................................................................44
6.2.2. Allocation to Investigational Product .........................................................44
6.3. Study Intervention Compliance...............................................................................44
6.4. Concomitant Therapy..............................................................................................45
6.4.1. Prohibited Medications...............................................................................45
6.4.2. Treatment(s) for Bleeding Episodes...........................................................46
6.5. Dose Modification...................................................................................................47
6.6. Intervention After the End of the Study..................................................................47
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................47
7.1. Discontinuation of Study Intervention ....................................................................47
7.2. Participant Discontinuation/Withdrawal From the Study.......................................47
7.2.1. Withdrawal of Consent:..............................................................................48
7.3. Lost to Follow-up....................................................................................................49
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................49
8.1. Efficacy Assessments..............................................................................................51
8.2. Safety Assessments .................................................................................................51
8.2.1. Physical Examinations................................................................................51
8.2.2. Vital Signs ..................................................................................................51
8.2.3. Electrocardiograms.....................................................................................52
8.2.4. Clinical Safety Laboratory Assessments ....................................................52
8.2.5. Injection Site Reaction................................................................................53
8.3. Adverse Events and Serious Adverse Events..........................................................53
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......54
8.3.2. Method of Detecting AEs and SAEs ..........................................................54
8.3.3. Follow-up of AEs and SAEs.......................................................................55
8.3.4. Regulatory Reporting Requirements for SAEs...........................................55
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................55
8.3.6. Cardiovascular and Death Events...............................................................56
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................56

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8.3.8. Adverse Events of Special Interest.............................................................57
8.3.9. Medical Device Deficiencies......................................................................57
8.3.10. Medication Errors.....................................................................................58
8.4. Treatment of Overdose............................................................................................59
8.5. Pharmacokinetics ....................................................................................................59
8.5.1. Analysis of PK PF-06741086 Concentration .............................................59
8.4.2 Analysis of Anti-PF-06741086 Antibodies and Neutralizing 
Antibodies to PF-06741086.............................................................................60
8.6. Pharmacodynamics..................................................................................................61
8.6.1. Tissue Factor Pathway Inhibitor.................................................................62
8.6.2. Thrombin Generation Assay.......................................................................62
8.6.3. Prothrombin Fragment 1 and 2 (PF1+2) and Dilute Prothrombin 
Time (dPT).......................................................................................................62
8.6.4. D-dimer.......................................................................................................62
8.7. Genetics...................................................................................................................63
8.7.1. Specified Genetics ......................................................................................63
8.7.2. Banked Biospecimens for Genetics............................................................63
8.8. Biomarkers ..............................................................................................................63
8.8.1. Specified Gene Expression (RNA) Research .............................................63
8.8.2. Specified Protein Research.........................................................................63
8.8.3. Specified Metabolomic Research ...............................................................63
8.8.4. Banked Biospecimens for Biomarkers .......................................................63
8.9. Health Economics ...................................................................................................63
9. STATISTICAL CONSIDERATIONS ................................................................................63
9.1. Estimands and Statistical Hypotheses.....................................................................63
9.2. Sample Size Determination.....................................................................................64
9.3. Populations for Analysis .........................................................................................64
9.4. Statistical Analyses .................................................................................................64
9.4.1. Pharmacokinetic Analysis ..........................................................................64
9.4.2. Pharmacodynamic Analysis........................................................................65
9.5. Safety Analyses.......................................................................................................65
9.5.1. Electrocardiogram Analyses.......................................................................66
9.6. Interim Analyses .....................................................................................................66

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9.6.1. Data Monitoring Committee.......................................................................66
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................67
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............67
10.1.1. Regulatory and Ethical Considerations ....................................................67
10.1.2. Financial Disclosure .................................................................................68
10.1.3. Informed Consent Process ........................................................................68
10.1.4. Data Protection .........................................................................................69
10.1.5. Dissemination of Clinical Study Data ......................................................69
10.1.6. Data Quality Assurance ............................................................................70
10.1.7. Source Documents....................................................................................72
10.1.8. Study and Site Closure..............................................................................72
10.1.9. Publication Policy.....................................................................................72
10.1.10. Sponsor’s Qualified Medical Personnel .................................................73
10.2. Appendix 2: Clinical Laboratory Tests .................................................................74
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................76
10.3.1. Definition of AE .......................................................................................76
10.3.2. Definition of SAE.....................................................................................77
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................78
10.3.4. Reporting of SAEs....................................................................................81
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................................83
10.5. Appendix 5:  Genetics...........................................................................................85
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........86
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................88
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting..............................................90
10.8.1. Definition of AE and ADE .......................................................................90
10.8.2. Definition of SAE, SADE, and Unanticipated Serious Adverse 
Device Effect ...................................................................................................90
10.8.3. Definition of Device Deficiency...............................................................91

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Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 
To determine the safety and 
tolerability of a single SC dose of PF-
06741086 administered to Chinese 
adult participants with severe 
hemophilia A or B, with or without 
inhibitors.

Frequency, severity and causal 
relationship of treatment emergent 
adverse events (TEAEs)  and 
withdrawals due to TEAE; Day 1 up 
to Day 42.

Frequency and magnitude of 
abnormal laboratory findings 
(including hematology, prothrombin 
time (PT)/ international normalized 
ratio (INR), activated partial 
thromboplastin time (APTT), 
chemistry, urinalysis, fibrinogen, 
anti-thrombin III (ATIII) activity and 
cardiac troponin I (cTnI)); Day 1 up 
to Day 28.

Changes from baseline in vital sign 
(blood pressure, pulse rate, 
temperature and respiration rate) 
measurements, 12-lead
electrocardiogram (ECG) parameters 
and physical examination; Day 1 up 
to Day 28.

Frequency, severity and causal 
relationship of injection site 
reactions; Day 1 up to Day 7.
Secondary: 
Secondary: 

To characterize the PK profile of a 
single SC dose of PF-06741086.

To characterize the PD profile of a 
single SC dose of PF-06741086.

Plasma PF-06741086 concentrations 
as determined by a validated assay 
from Day 1 up to Day 28, and 
noncompartmental PK parameters 
including peak or maximum observed 
concentration (Cmax), time to reach 
maximum concentration (Tmax), area 
under the concentration-time curve 
from time 0 to the time of the last 
quantifiable concentration (AUClast), 
area under the concentration-time 
curve from time 0 to infinity 
(AUCinf), terminal half-life, apparent 
volume of distribution (Vz/F), 
apparent clearance (CL/F).

TFPI (total and free); Thrombin 
generation (including lag time, peak 
thrombin generation and endogenous 
thrombin generation potential); 
Prothrombin fragment 1+2 (PF1+2);

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
To characterize the immunogenicity 
of a single SC dose of PF-06741086.
D-dimer; Dilute prothrombin time
(dPT); Day 1 up to Day 28.

Frequency of anti-drug antibody 
(ADA) and neutralizing antibody 
(NAb) production against 
PF-06741086; Day 1 up to Day 28.  
Only positive ADA samples and the 
corresponding baseline sample will be 
tested in the NAb assay.
Overall Design
This is a Phase 1, single-arm, open-label, non-randomized, non-controlled, multicenter  study 
in 6 Chinese adult participants between ages 18 to <75 years with severe hemophilia A or B 
(defined as Factor VIII (FVIII) or Factor IX (FIX) activity <1%, respectively), with or without 
inhibitor. This study aims to evaluate the PK, PD, safety and tolerability of a single
subcutaneous (SC) dose of PF-06741086.
Number of Participants
Approximately 6 participants are planned for enrollment at 2 study sites. 
Intervention Groups and Duration
Participants who meet the selection criteria will accept a single SC injection of 300 mg PF-
06741086 and go through a 7 day evaluation after dosing (including intensive PK) while 
confined in the study center. Following this 7 day period, all participants will return for 
outpatient follow-up visits once a week to Day 42 per Schedule of Activities. The total duration 
of the study for a single subject, from initial screening to final follow-up, will be approximately 
2.5 months.
Data Monitoring Committee: No
Statistical Methods
Statistical objective is exploratory. Descriptive analyses will be performed.
1.2. Schema
Not applicable.

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or FIX.
Potential Risks 
Individuals may experience risks or discomforts at the anatomical site of SC injection with PF-
06741086. Injection Site Reactions, which may include pain, swelling, bruising, induration, and 
hematoma, are considered adverse drug reactions for PF-06741086. 
Potential risks for treatment with PF-06741086 are thrombi or emboli. Depending on location 
and severity, thrombi or emboli may be life threatening or fatal. 
Because PF-06741086 is a fully human IgG1 with no endogenous counterpart, the anti-drug 
antibody response (ADA) is expected to primarily affect the PK, efficacy and/or measurement of 
PF-06741086. An additional potential immunogenicity risk is the ADA-induced hypersensitivity. 
Therefore, individuals with a diagnosis or history of thrombotic or ischemic disease (including 
myocardial infarction, deep venous thrombosis or pulmonary embolism), individuals with 
coronary artery disease and individuals with an allergy to hamster protein should be excluded 
from study participation. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of PF-06741086 may be found in the investigator’s brochure
(IB), which is the single reference safety document (SRSD) for this study. 

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3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 
To determine the safety and 
tolerability of a single SC dose of PF-
06741086 administered to Chinese 
adult participants with severe 
hemophilia A or B with or without 
inhibitors.

Frequency, severity and causal 
relationship of treatment emergent 
adverse events (TEAEs)  and 
withdrawals due to TEAE; Day 1 up 
to Day 42.

Frequency and magnitude of 
abnormal laboratory findings 
(including hematology, PT/INR, 
APTT, chemistry, urinalysis, 
fibrinogen, ATIII activity and 
cardiac troponin I); Day 1 up to Day 
28.

Changes from baseline in vital signs 
(blood pressure, pulse rate, 
temperature and respiration rate) 
measurements 12-lead
electrocardiogram (ECG) parameters 
and physical examination; Day 1 up 
to Day 28.

Frequency, severity and causal 
relationship of injection site 
reactions; Day 1 up to Day 7.
Secondary: 
Secondary: 

To characterize the PK profile of a SC 
single dose of PF-06741086.

To characterize the PD profile of a SC 
single dose of PF-06741086.

To characterize the immunogenicity 
of a single SC dose of PF-06741086.

Plasma PF-06741086 concentrations 
as determined by a validated assay 
Day 1 up to Day 28, and 
noncompartmental PK parameters 
including Cmax, Tmax, AUClast, AUCinf, 
terminal half-life, Vz/F, CL/F.

TFPI (total and free); Thrombin 
generation (including lag time, peak 
thrombin generation and endogenous 
thrombin generation potential); 
Prothrombin fragment 1+2 (PF 1+2);
D-dimer; Dilute prothrombin time
(dPT); Day 1 up to Day 28.

Frequency of anti-drug antibody 
(ADA) and neutralizing antibody 
(NAb) production against 
PF-06741086; Day 1 up to Day 28.  
Only positive ADA samples and the 
corresponding baseline sample will be 
tested in the NAb assay.

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
Documentation of current high titer inhibitor (≥5 BU/mL) or current low titer 
inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or 
FIX recovery <60% of expected within previous 4 months  prior to screening.

Participants with on-demand treatment regimen with ≥6 bleeding episodes 
(spontaneous and/or traumatic) necessitating treatment with bypass factor for at 
least 4 months prior to screening and willing to continue to receive on-demand 
treatment during the study. Surgical bleeding episodes do not apply to this criterion.
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 informed consent 
document (ICD) and in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Previous or current treatment for and/or history of coronary artery diseases, venous or 
arterial thrombosis (Common Terminology Criteria for Adverse Events [CTCAE]13
Grade >1), or ischemic disease (except treatment for catheter-associated thrombosis).
2. Known planned surgical procedure during the planned study period.
3. Known hemostatic defect other than hemophilia A or B.
4. Abnormal renal or hepatic function as defined by the following laboratory results at 
Screening:
a.
Alanine transaminase (ALT) >2 × upper limit of normal (ULN).
b. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin 
is fractionated and direct bilirubin <35%).
c.
Current unstable liver or biliary disease per investigator assessment defined by 
the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, 
oesophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable 
chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, 
and chronic stable hepatitis B or C -eg, presence of hepatitis B surface antigen 
[HbsAg] or positive hepatitis C antibody test result at screening or within 3 
months prior to starting study intervention) is acceptable if the participant 
otherwise meets entry criteria.
d. Serum albumin less than the lower limit of normal (LLN).
e.
Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.
5. Abnormal hematology values as defined by the following laboratory tests at Screening:
a.
Platelet count <100,000/Ul
b. Fibrinogen level <LLN
c.
Hemoglobin level <10 g/Dl

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6. Abnormal coagulation activity as defined by the following laboratory results at 
Screening:
a.
Prothrombin time (PT) >1.25 × ULN.
7. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.
8. Corrected QT interval (QTc) >450 msec for male participants or QTc >480 msec in 
participants with bundle branch block.
9.
Individuals with hypersensitivity or an allergic reaction to hamster protein or other 
components of the study intervention. 
10. A positive urine drug screen.
Prior/Concomitant Therapy:
11. Current routine prophylaxis with bypassing agent (eg, activated prothrombin complex 
concentrate (aPCC), Prothrombin Complex Concentrates [PCC], and/or rFVIIa) or non
coagulation factor-replacement therapy (eg, emicizumab).
12. Regular, concomitant therapy with immunomodulatory drugs (eg, IV immunoglobulin 
[IVIG], and routine systemic corticosteroids, rituximab).
13. Ongoing or planned use of immune tolerance induction during the study phase, or 
prophylaxis with FVIII or FIX replacement during the study.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving investigational drug(s) within 30 days (or as 
determined by local requirements) or 5 half-lives prior to study entry and/or during 
study participation. 
Diagnostic Assessments:
15. CD4 cell count ≤200/Ul if human immunodeficiency virus (HIV)-positive
16. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results.
Other Exclusions:
17. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or Pfizer 
employees, including their family members, directly involved in the conduct of the 
study. 

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5.3. Lifestyle Considerations
No lifestyle restrictions are required.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently entered in the study.  A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities.  Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE).
Screen failure data are collected and remain as source and are not reported to the clinical 
database.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  Rescreened participants should be assigned the same participant number as for the 
initial screening.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used synonymously 
with study intervention.
6.1. Study Intervention(s) Administered
ARM Name
PF-06741086
Intervention Name
PF-06741086
Type
Biological product
Dosage Form
Injectable
Dosage
300 mg once a
Route of Administration
Subcutaneous injection
b
IMP and NIMP c
IMP
Sourcing
Provided centrally by the sponsor
Packaging and Labeling
Study Intervention will be provided in a sterile liquid 
solution for injection packaged in a prefilled syringe for 
single use. Each package will be labeled as required per 
country requirement.
b. Following an overnight fast of least 10 hours, participants will receive PF-06741086 by SC injection at approximately 
0800 hours (plus or minus 2 hours).  All participants will be required to refrain from lying down (except when required for 
blood pressure, pulse rate, and ECG measurements), eating, and drinking beverages other than water during the first 4 hours 
CCI
CCI

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7. See the investigational product manual (IP manual) for storage conditions of the study 
intervention once reconstituted and/or diluted.
8. Any excursions from the study intervention label storage conditions should be reported 
to Pfizer upon discovery along with any actions taken.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention 
must be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use 
of the study intervention after the temperature excursion. Use of the study intervention 
prior to Pfizer approval will be considered a protocol deviation. Specific details 
regarding the definition of an excursion and information the site should report for each 
excursion will be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator 
site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer, and all destruction must be adequately documented.
6.2.1. Preparation and Dispensing 
See the investigational product manual (IP manual) for instructions on how to prepare the 
investigational product for administration.  Investigational product should be prepared and 
dispensed by an appropriately qualified and experienced member of the study staff (eg, 
physician, nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, or 
pharmacist) as allowed by local, state, and institutional guidance.
6.2.2. Allocation to Investigational Product
This is an open-label, single-arm study. The investigator’s knowledge of the treatment should 
not influence the decision to enroll a particular participant or affect the order in which 
participants are enrolled.
The investigator will assign participant identification numbers sequentially to the participants 
as they are screened for the study. This identifying number will be retained throughout the
study. A participant identifying number must never be reassigned or reused for any reason. 
Study intervention will be dispensed at the study visits summarized in the Schedule of 
Activities (SoA).
Returned study intervention must not be redispensed to the participants.
6.3. Study Intervention Compliance
Participant compliance with investigational product will be assessed.  

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Compliance will be assessed by direct questioning.  Deviation(s) from the prescribed dosage 
regimen should be recorded in the case report form (CRF).
All doses of investigational product will be administered by the appropriately designated study 
staff at the investigator site.
6.4. Concomitant Therapy
Participants will abstain from all prohibited concomitant medications, except for the treatment 
of adverse events or acute bleeding episodes as described in Section 6.4.1 of this protocol.
All concomitant treatments taken during the study must be recorded with indication, and start 
and stop dates of administration. All participants will be questioned about concomitant 
treatments at each clinic visit. If a participant receives a prohibited concomitant medication 
during their participation in the study, the participant’s continued participation in the study will 
be decided on a case-by-case basis, at the discretion of the investigator and sponsor.
For emergency or unplanned surgical interventions, investigators must contact the sponsor’s 
medical monitor as soon as possible to review concomitant treatments and any impact on 
participant participation.
Treatments taken within 28 days prior to informed consent being signed will be documented 
as a prior treatment. Treatments taken from date of signed informed consent will be 
documented as concomitant treatments.
6.4.1. Prohibited Medications
Factor VIII (within 72 hours) or Factor IX replacement therapy (within 96 hours), extended 
half-life FVIII or FIX replacement therapy (within 4 x half-life) or bypass agent therapy 
(rFVIIa, PCC or aPCC: within 72 hours) before Screening is prohibited. Depending on the 
coagulation factor product in use, additional wash out time may be required prior to the 
screening assessments to achieve a factor activity level ≤1%. If a participant experiences an
acute bleeding episode during this washout period requiring treatment with a Factor VIII or IX 
replacement therapy, or bypass agent therapy, the participant is to be stabilized utilizing this
regimen and a new washout period should be initiated. The regimen used to treat the episode
should be recorded as a prior medication.
Factor VIII (within 72 hours) or Factor IX replacement therapy (within 96 hours), extended 
half-life FVIII or FIX replacement therapy (within 4 x half-life)  or bypass agent therapy (for 
rFVIIa, PCC or aPCC: at least 72 hours) before Day 1 treatment is also prohibited. If a 
participant experiences an acute bleeding episode during this washout period requiring 
treatment with a Factor VIII or IX replacement therapy, or bypass agent therapy the participant 
is to be stabilized utilizing this regimen and a new washout period should be initiated. The 
regimen used to treat the episode should be recorded as a concomitant medication. All acute 
bleeding episodes between Screening and Day 1 must be recorded. Treatment with rFVIIa at 
a dose level greater than approximately 90 ­g/kg and to exceed a dosing frequency of 
approximately every 2 hours is prohibited throughout the study. If a participant receiving 
investigational product is subsequently administered a rFVIIa dose greater than approximately 
90 μg/kg or more frequent than every 2 hours, the investigator must immediately contact the 

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sponsor’s medical monitor to discuss the case to determine if the respective participant should 
continue to receive IP, remain in the study, or be withdrawn  immediately.
The following are prohibited throughout the study: immunomodulatory medications (eg, IVIG, 
routine systemic corticosteroids, rituximab), emicizumab, aPCC. Bypassing agent therapy is 
not permitted at any time for participant without inhibitor. 
The use of antifibrinolytic agents or medications known to influence platelet function (eg, 
aspirin, certain non-steroidal anti-inflammatory drugs (NSAIDs) or certain traditional Chinese 
medicines (TCMs)) within 5 days before initial study drug administration through Day 42 is 
prohibited.
6.4.2. Treatment(s) for Bleeding Episodes
Bleeding episodes that occur during this study may be treated (on-demand) with hemostatic
therapy (recommend intravenous factor products for participants without inhibitors; rFVIIa 
bypass agent therapy at approximately 90 µg/kg and not to exceed a dosing frequency of every 
2 hours for participants with inhibitors; or PCC at the lowest effective dose, in accordance with 
the Product Prescribing Information) as deemed appropriate by the investigator. The specific 
treatment with hemostatic therapy is at the discretion of the subject/caregiver/investigator, but 
all doses of hemostatic therapy taken after signing of informed consent will be documented as 
concomitant medications or concomitant treatments.
If a participant experiences a bleeding episode during the washout period preceding screening
laboratory assessments, the participant is to be stabilized utilizing the participant’s usual 
hemostatic treatment regimen. Once the bleeding episode has been successfully treated a new 
washout period should be completed prior to obtaining the screening laboratory tests.
If a participant experiences a bleeding episode during the washout period preceding the initial
administration of PF-06741086 the participant is to be stabilized utilizing the participant’s 
usual hemostatic treatment regimen and a new washout period should be implemented. Once
treatment of the bleeding episode with hemostatic agents has been completed a new washout
period should be initiated in anticipation of the initial treatment with PF-06741086.
If a participant experiences a bleeding episode during the PK assessment period following
administration of PF-06741086, the participant is to be stabilized utilizing the Factor VIII or 
Factor IX treatment regimen at the lowest effective dose according to the approved Product 
Prescribing Information, or rFVIIa bypass agent therapy at approximately 90 µg/kg and not 
to exceed a dosing frequency of every 2 hours, or PCC at the lowest effective dose, in 
accordance with the Product Prescribing Information, and protocol specified observations 
and procedures should proceed to completion.  
If a participant experiences a bleeding episode after Day 28 following the initial
administration of PF-06741086, the participant is to be stabilized utilizing the participant’s 
usual hemostatic treatment regimen.
Treatment with aPCC or other plasma product (eg: Fresh frozen plasma or cyoprecipitate) in 
accordance with approved product labeling may be allowed only in the following scenarios in 
cases where such treatment is considered medically necessary during an emergency situation:

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
rFVIIa provides insufficient control of participant’s bleeding;

in the absence of suitable hemostatic medication.
The use of hemostatic medications for bleeding episodes as specifically outlined in this Section 
(6.4.2) is not considered to be a protocol violation.
6.5. Dose Modification 
Not Applicable. 
6.6. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Since this is a single-dose study, this section is not applicable.
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his 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 (visit Day 7) 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 termination visit applies only to participants who are enrolled 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 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.

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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.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Clinical Trial (CT) SAE Report.
The investigator should inquire about the reason for withdrawal, request that the participant 
return for a final visit, if applicable, and follow-up with the participant regarding any
unresolved adverse events (AEs).
It may be appropriate for the participant to return to the clinic for final safety assessments to 
be scheduled as early as practically feasible following the decision to withdraw from the study.
Participants should be questioned regarding their reason for withdrawal. At the early 
withdrawal visit, every effort must be made to complete the following assessments:
Brief physical examination, if there is a new or open AE or clinically significant
abnormal physical finding from the last visit;

Assess heart rate, respiration rate, temperature and supine blood pressure;

Single 12-lead ECG measurement (if ECG is abnormal, collect triplicate ECG);

Obtain blood and urine samples for the following laboratory tests;

Hematology (details in Table 6);

Serum chemistry (details in Table 6);

PT/INR;

APTT;

Anti-thrombin III;

Fibrinogen;

Cardiac Troponin I (only if withdrawal is prior to CRU discharge/Day 7);

TFPI (total and free) levels;

Thrombin Generation;

Prothrombin fragment 1 + 2;

D-dimer;

Dilute prothrombin time (dPT);

Urinalysis;

Pharmacokinetic (PK) analysis;

Immunogenicity (ADA, NAb).
Lack of completion of all or any of the withdrawal/early termination 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 treatment will remain in the study and 
must continue to be followed for protocol specified followup 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.  

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Participants should notify the investigator in writing of the decision to withdraw consent from 
future follow-up, whenever possible.  The withdrawal of consent should be explained in detail 
in the medical records by the investigator, as to whether the withdrawal is only from further 
receipt of investigational product or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page.  In the event that vital status (whether the 
participant is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if they repeatedly fail 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, they will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA.  Protocol waivers or exemptions 
are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to record 

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details of all participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and shipment 
instructions and contact information will be provided to the investigator site prior to initiation 
of the study.
The total blood sampling volume for individual participants in this study is approximately 
289.2 mL. Table 3 reflects approximate sample volumes needed for each measured endpoint. 
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 30 consecutive days.
Table 3.     Blood Volume
Sample Type
Sample
Volume (mL)
Number of Sampling Times
Total
Volume 
(mL)
Screening
Study
Period
Follow
-Up
Safety Labs:
           67
FVIII or FIX activity
2.7 
1
1
5.4
FVIII or FIX inhibitora
2.7 
1
2.7
Serum chemistry (with Lipid profilea)
4
1
3
0
16
Hematology
2
1
3
0
8
Serology (HbsAg, HBc Ab, HCV Ab, and HIV)a
5
1
0
0
5
APTT, PT/INR, Fibrinogen, 
2.7 (combined)
1
3
3
            18.9
Anti-thrombin III
Cardiac Troponin I
3
0
3
0
9
Other Screening a:
10
Protein C activity, protein S level, 
5
1
0
0
5
Factor V Leiden mutation, Prothrombin 20210 
mutation
5
1
0
0
5
PK: PF-06741086 concentration
4.5
0
8
3
49.5
Immunogenicity: (ADA, NAb)
9.0
0
1
3
36.0
PD biomarkers:
128.7
TFPI (total and free) levels
2.7
0
8
3
29.7
TGA
2.7
0
8
3
29.7
PF1+2, dPT
4.5 (combined)
0
8
3
49.5
D-dimer
1.8
0
8
3
19.8
TOTAL
289.2

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a at Screening only.
This total volume does not include discarded blood from pre-draws used to remove fluid from flushed, if
applicable.
8.1. Efficacy Assessments
Not applicable.
8.2. Safety Assessments
8.2.1. Physical Examinations

A complete physical examination will include, at a minimum, assessments of the head, 
ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, 
musculoskeletal, and neurological systems. Height and weight will also be measured and 
recorded. 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. 

A brief physical examination will include, at a minimum, assessments of the general
appearance, the respiratory and cardiovascular systems, as well as participant reported 
symptoms.

Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. Vital Signs

Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed. Blood 
pressure and pulse measurements will be assessed in a resting position (either seated or 
supine) with a completely automated device. Manual techniques will be used only if an 
automated device is not available.

Blood pressure, respiratory rate, and pulse measurements should be preceded by at least 5 
minutes of rest for the participant in a quiet setting without distractions (eg, television, cell 
phones).

Respiratory rate should be measured by observing and counting the respirations of the 
participant for 30 seconds and multiplied by 2. When blood pressure is to be taken at the 
same time, measurement should be done during the 5 minutes of rest and before blood 
pressure measurement.

No eating, drinking, or smoking is allowed for 15 minutes prior to the measurement of 
oral temperature.

Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse 
and 3 blood pressure measurements (3 consecutive blood pressure readings will be 
recorded at intervals of at least 1 minute). The average of the 3 blood pressure readings 

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will be recorded on the CRF.
8.2.3. Electrocardiograms

Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT 
intervals.

At each time point at which triplicate ECG are required (ie, when single ECG is abnormal 
or when troponin I is abnormal), 3 individual ECG tracings should be obtained 
approximately 2-4 minutes apart.
Single 12-lead ECGs are performed for all participants in a supine position. If a single time
point ECG is abnormal (see Appendix 7 for examples of abnormal results), then a triplicate
ECG is required. When done in triplicate, ECGs will be obtained approximately 2-4 minutes
apart; the average of the triplicate ECG measurements collected at pre-dose Day1 will serve as 
each participant’s baseline value.
Sites with the cTnI assay available at their local laboratory will collect cTnI samples for central 
and local analysis. If cTnI results are abnormal, the investigator should consult with a
cardiologist concerning cTnI and ECG results, and outcome of cardiac consult is then
discussed with the Pfizer medical monitor to determine appropriate course of action. When
possible, the participant should return within 24 hours for repeated cTnI sample collection.
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead
placement as contributing to the ECG abnormality. It is important that leads are placed in the
same positions each time in order to achieve precise ECG recordings.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.4. 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.
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 28 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.

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All protocol required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the the SoA.
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the CRF.
Any remaining serum/plasma from samples collected for clinical safety labs at baseline and at 
all times post-dosing may be retained and stored for the duration of the study.
8.2.5. Injection Site Reaction
Injection site reactions will be assessed after single dose of PF-06741086 and according to 
the Schedule of Activities. Injection site reactions will be measured using the Common 
Terminology Criteria for Adverse Events (CTCAE), Version 5.0.13 These measurements 
will be categorized by CTCAE Grades 1-5 (Table 4).
Table 4.     Common Terminology Criteria for Adverse Events for Injection Site Reactions
Grade 1
Tenderness with or without associated symptoms (eg, warmth, erythema, itching)
Grade 2
Pain, lipodystrophy, edema, phlebitis
Grade 3
Ulceration or necrosis, severe tissue damage, operative intervention indicated
Grade 4
Life-threatening consequences, urgent intervention indicated
Grade 5
Death
If deemed appropriate by the investigator, a consultation with a dermatologist will be
performed. Documentation may include a dermatologist report, clinic notes and photographs.
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 it meets 
the criteria for classification as an SAE or that caused the participant to discontinue the study 
intervention/study (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.

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8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection period”) 
for each participant begins from the time the participant provides informed consent, which is 
obtained before the participant’s participation in the study (ie, before undergoing any study 
related procedure and/or receiving investigational product), through and including a minimum 
of 42 calendar days after the last administration of the study intervention.
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 AEs or SAEs after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
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 as described in Section 
8.3.1 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.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.2.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.

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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, institutional review boards (IRBs)/ethics committees (ECs), and 
investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file 
it along with the with the SRSD(s) for the study and will notify the IRB/EC, if appropriate 
according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy and occupational
exposure are reportable to Pfizer Safety within 24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female partners of male participants will be collected after the 
start of study intervention and until 28 days after the last dose.

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If a pregnancy is reported, the investigator should inform the sponsor within [24 hours] of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 
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.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s
awareness, using the CT SAE Report Form, regardless of whether there is an associated SAE.
Since the information does not pertain to a participant enrolled in the study, the information is 
not recorded on a CRF; however, a copy of the completed CT SAE Report Form is maintained 
in the investigator site file
8.3.6. Cardiovascular and Death Events
Any cardiovascular events and deaths will be assessed on a case by case basis through duration 
of the study.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
The following disease-related events (DREs) are common in participants with hemophilia A 
or B and can be serious/life threatening:

Bleeding, pain, swelling, or decreased range of motion due to a bleed
Certain events, due to the participant’s hemophilia, will be recorded as a DRE. Investigators 

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should determine if an event is expected because of the participant’s hemophilia. But bleeding 
or bruising, not due to paticipants’ hemophilia, should be recorded as an AE, not a DRE.
Because these events are typically associated with the disease under study, they will not be
reported according to the standard process for expedited reporting of SAEs even though the
event may meet the definition of a SAE. These events will be recorded on the SAE CRF page
in the participant’s CRF within 24 hours.
NOTE: However, if either of the following conditions applies, then the event must be recorded 
and reported as an SAE (instead of a DRE):

The event is, in the investigator’s opinion, of greater intensity, frequency, or
duration than expected for the individual participant.
OR

The investigator considers that there is a reasonable possibility that the event was
related to study intervention.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.9. Medical Device Deficiencies
Medical devices are being provided for use in this study as a prefilled syringe for the purposes 
of administering study intervention. In order to fulfill regulatory reporting obligations
worldwide, the investigator is responsible for the detection and documentation of events
meeting the definitions of device deficiency that occur during the study with such devices.
The definition of a medical device incident can be found in Appendix 8.
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.3.1 through 8.3.4 and Appendix 3 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Incidents
Medical device deficiencies of the device that result in an incident will be detected, 
documented, and reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator will promptly notify the sponsor.
The method of documenting medical device incidents is provided in Appendix 8.
8.3.9.2. Follow-up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the incident.

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New or updated information will be recorded on a follow-up form with all changes signed and 
dated by the investigator.
8.3.9.3. Prompt Reporting of Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency. 
Information will be provided to the sponsor as described in the IP Manual. 
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Section 8.3.1.1 and 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating 
to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.

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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 an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of PF-06741086 greater than 600 mg within a 6 day (144-hour) time 
period 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 immediately.
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 study intervention 
(whichever is longer).
3. Obtain 2 blood samples (7 days apart) for pharmacokinetic (PK) analysis within 7 days 
from the date of the last dose of study intervention if requested by the medical monitor
(determined on a case-by-case basis).
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics 
8.5.1. Analysis of PK PF-06741086 Concentration
If an arm is used for the SC injection, the opposite arm should be used for the PK/PD blood 
sample collections, if possible. 
During all study periods, blood samples (4.5 mL) to provide approximately 2 mL plasma for 
PK analysis will be collected into appropriately labeled tubes containing sodium citrate at times 

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8.7. Genetics
8.7.1. Specified Genetics
A 5 mL blood sample for DNA isolation will be collected. DNA samples will be analyzed for 
the purpose of assessing Factor V Leiden mutation and prothrombin 20210 mutation only at 
screening. No other genetic assessments are conducted.
8.7.2. Banked Biospecimens for Genetics
Banked biospecimen collection is not included in this study.
8.8. Biomarkers
Collection of samples for biomarker research is also part of this study. 
The following samples for biomarker research are required and will be collected from all 
participants in this study as specified in the SoA:
8.8.1. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study.
8.8.2. Specified Protein Research 
Specified protein research is not included in this study.
8.8.3. Specified Metabolomic Research 
Specified metabolomic research is not included in this study.
8.8.4. Banked Biospecimens for Biomarkers
Banked biospecimen collection is not included in this study.
8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
There are no statistical hypotheses and estimands are not applicable.

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regression of the log-linear 
concentration-time curve.  
AUClast
Area under the plasma 
concentration-time profile from time 
zero to the time of the last quantifiable 
concentration (Clast)
Linear/Log trapezoidal method
AUCinf
Area under the plasma 
concentration-time profile from time 
zero extrapolated to infinite time
AUClast + (Clast/kel),
where Clast is the predicted plasma 
concentration at the last quantifiable time 
point estimated from the log-linear 
regression analysis.
CL/F
Apparent clearance
Dose/AUCinf
Vz/F
Apparent volume of distribution
Dose/ (AUCinf*kel)
Actual PK sampling times will be used in the derivation of PK parameters. 
9.4.2. Pharmacodynamic Analysis
The PD endpoints include TFPI (total and free), dPT, PF1+2, D-dimer, and thrombin 
generation (parameters may include lag time, peak thrombin generation, and endogenous 
thrombin generation potential).  These PD endpoints will be listed and summarized 
descriptively by sampling time. 
Maximum change from baseline and area under effect curve for change from baseline PD 
values may be summarized if data allow. 
Parameter
Definition
Method of Determination
MaxEff
Maximum PD change from baseline
Observed directly from data
AUEC
Area under the PD change from 
baseline-time profile from time zero to 
Day 28
Linear/Linear trapezoidal method
PK and PD data from this study will also be included in separate population PK and PK/PD 
analyses.   The population PK and PK/PD analyses will be presented separately from the 
main CSR.
9.5. Safety Analyses
All safety analyses will be performed on the safety population.
AEs, ECGs, blood pressure (BP), pulse rate, weight, and safety laboratory data (including 
chemistry, hematology, PT/INR, APTT, urinalysis, fibrinogen, anti-thrombin III activity, and 
cardiac troponin I) 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 descriptively, where appropriate.
Immunogenicity (ADA, NAb) results will be listed (including titers) by timepoint.

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9.5.1. 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.
The number (%) of participants with maximum postdose QTcF 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.
If more than 1 ECG is collected at a nominal time after dose administration (for example, 
triplicate ECGs), the mean of the replicate measurements will be used to represent a single 
observation at that time point.  If any of the 3 individual ECG tracings has a QTcF value 
>500 msec, but the mean of the triplicates is not >500 msec, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500-msec value in appropriate clinical context.  However, values from individual tracings 
within triplicate measurements that are >500 msec will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 msec. 
Changes from baseline will be defined as the change between the post dose QTcF value and 
the average of the time -matched baseline triplicate values on Day 1, or the average of the 
pre-dose triplicate values on Day 1.  
9.6. Interim Analyses
No interim analyses will be performed. As this is an open label study, the sponsor may 
conduct unblinded reviews of the data during the course of the study for the purpose of safety 
assessment, facilitating PK/PD modeling and supporting clinical development.
9.6.1. Data Monitoring Committee 
This study will not use a data monitoring committee (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 Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines;
•
Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
guidelines;
•
Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, investigator’s brochure (IB), and other relevant 
documents (eg, advertisements) must be reviewed and approved by the sponsor and submitted 
to an IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study 
is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:
•
Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;
•
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
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.
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, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC or study 
center.
The investigator must ensure that each study participant or his 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 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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10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only authorized 
study staff have access.  The study site will implement appropriate technical and organizational 
measures to ensure that the personal data can be recovered in the event of disaster.  In the event 
of a potential personal data breach, the study site shall be responsible for determining whether 
a personal data breach has in fact occurred and, if so, providing breach notifications as required 
by law.
To protect the rights and freedoms of natural persons with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code.  Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred.  All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code.  The study site will maintain 
a confidential list of participants who participated in the study, linking each participant’s 
numerical code to his or her actual identity.  In case of data transfer, the sponsor will protect 
the confidentiality of participants’ personal data consistent with the clinical study agreement 
and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs).
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.

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EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of the 
PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used to 
identify individual participants have been removed) on www.pfizer.com for Pfizer-sponsored 
interventional studies at the same time the US Basic Results document is posted to 
www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, under
Phase 2 of this policy, includes the publishing of individual participant data.  Policy 0070 
applies to new marketing authorization applications submitted via the centralized procedure 
since 01 January 2015 and applications for line extensions and for new indications submitted 
via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes of 
“bona-fide scientific research” that contribute to the scientific understanding of the disease, 
target, or compound class.  Pfizer will make available data from these trials 24 months after 
study completion.  Patient-level data will be anonymized in accordance with applicable privacy 
laws and regulations.  CSRs will have personally identifiable information redacted.
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 onsite monitoring), are provided in the study 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 electronic CRF (eCRF) that are transcribed from 
source documents must be consistent with the source documents or the discrepancies must be 
explained.  The investigator may need to request previous medical records or transfer records, 
depending on the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in monitoring plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/EC or 
local health authorities, the sponsor’s procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications such 
as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 30 days 
before submission.  This allows the sponsor to protect proprietary information and to provide 
comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer intervention-related 
information necessary for the appropriate scientific presentation or understanding of the study 
results.

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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 supporting study documentation.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational product identifiers, participant numbers, contact 
information for the investigator site, and contact details for a contact center in the event that 
the investigator site staff cannot be reached to provide advice on a medical question or problem 
originating from another healthcare professional not involved in the participant’s participation 
in the study.  The contact number can also be used by investigator staff if they are seeking 
advice on medical questions or problems; however, it should be used only in the event that the 
established communication pathways between the investigator site and the study team are not 
available.  It is therefore intended to augment, but not replace, the established communication 
pathways between the investigator site and the study team for advice on medical questions or 
problems that may arise during the study.  The contact number is not intended for use by the 
participant directly, and if a participant calls that number, they will be directed back to the 
investigator site.

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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of the 
method of analysis or the type of analyzer used by the clinical laboratory; or as derived from 
calculated values.  These additional tests would not require additional collection of blood.  
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety concerns.
Table 6.
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/urea and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Lipid profileb
Ph
Glucose 
Protein 
Blood 
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopy& 
Culturea
HBsAgb
HBcAbb
HCVAbb
HIVb
CD4 cell countb
Anti-thrombin III
Protein C activityb
Protein S levelb
Factor 
V 
Leiden 
mutationb
Prothrombin 20210
Mutationb
PT/INR
APTT
Fibrinogen
Cardiac Troponin I
Factor VIII activityc
Factor IX activityc
Factor VIII and Factor 
IX
inhibitor b
urine drug screeningd
Additional Tests 
(Needed for Hy’s law)
AST, ALT (repeat)
Total bilirubin (repeat)
Albumin (repeat)
Alkaline phosphatase
(repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
Total bile acids
GGT
PT/INR
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = 
blood urea nitrogen; CO2 = carbon dioxide; HbsAg= hepatitis B surface antigen; HBc Ab=hepatitis B core 
antibody; HCV Ab=hepatitis C virus antibody;HIV=human immunodeficiency virus; MCH = mean corpuscular 
hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; 
RBC = red blood cell; WBC = white blood cell. 

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a.
Only if urinalysis is positive for blood, protein, leukocyte or nitrites.
b.
At Screening only.
c.
At Screening, Day 1 and Day 7 only
d.
At Screening and Day -1 only. Minimum requirement for drug screening includes: cocaine, 
tetrahydrocannabinol(THC), opiates/opioids, benzodiazepines and amphetamines.
Investigators must document their review of each laboratory safety report.

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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
No contraception methods are required for male participants in this study as there is no risk of 
teratogenicity/fetotoxicity.
Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:
•
A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or being 
exposed to the investigational product;
An example of environmental exposure would be a case involving direct contact with a Pfizer 
product in a pregnant woman (eg, a nurse reports that she is pregnant and has been exposed to 
chemotherapeutic products).
•
A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, 
regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the exposure.  
The information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for all 
EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural integrity 
of the terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.

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Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 
•
Spontaneous abortion includes miscarriage and missed abortion;
•
Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure to 
the investigational product. 
Additional information regarding the EDP may be requested by the sponsor.  Further follow-
up of birth outcomes will be handled on a case by case basis (eg, follow-up on preterm infants 
to identify developmental delays).  In the case of paternal exposure, the investigator will 
provide the participant with the Pregnant Partner Release of Information Form to deliver to his 
partner.  The investigator must document in the source documents that the participant was 
given the Pregnant Partner Release of Information Form to provide to his partner.

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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, susceptibility to, 
and severity and progression of disease.  Therefore, where local regulations and IRBs/ECs 
allow, a blood sample will be collected for DNA analysis.

The results of genetic analyses may be reported in the CSR or in a separate study summary, 
or may be used for internal decision making without being included in a study report.

The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 

The samples will be retained as indicated:
Samples for specified genetic analysis (see Section 8.7.1) will not be stored beyond the 
completion of this study.

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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a more 
serious potential outcome.  These participants fail to adapt and therefore are “susceptible” to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury (D
ILI).  Participants who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” or 
are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (Tbili) elevations (>2 × ULN) by several days 
or weeks.  The increase in Tbili typically occurs while AST/ALT is/are still elevated above 3 
× ULN (ie, AST/ALT and Tbili values will be elevated within the same laboratory sample).  In 
rare instances, by the time Tbili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to Tbili that meet the criteria outlined below are 
considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury have 
been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the participant’s 
individual baseline values and underlying conditions.  Participants who present with the 
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:
•
Participants with AST/ALT and Tbili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a Tbili value >2 × ULN 
with no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not 
available.
•
For participants with baseline AST OR ALT OR Tbili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:
Preexisting AST or ALT baseline values above the normal range: AST or ALT values >2 times 
the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller).
Preexisting values of Tbili above the normal range: Tbili level increased from baseline value 
by an amount of at least 1 × ULN or if the value reaches >3 × ULN (whichever is smaller).
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, creatine kinase (CK), direct and 
indirect bilirubin, gammaglutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase at the discretion of the 
investigator.  Consideration should also be given to drawing a separate tube of clotted blood 
and an anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by 
itself or as a coformulated product in prescription or over the counter medications), recreational 
drug, supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  Further 
testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and 
collection of serum sample for acetaminophen drug and/or protein adduct levels may be 
warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
Tbili elevation defined above should be considered potential DILI (Hy’s law) cases if no other 
reason for the liver function test (LFT) abnormalities has yet been found.  Such potential DILI 
(Hy’s law) cases are to be reported as SAEs, irrespective of availability of all the results 
of the investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of reasonable 
investigations have been received and have excluded an alternative etiology.

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10.9. Appendix 9: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ABR
annualized bleeding rate
Abs
Absolute
ADA
antidrug antibodies
ADCC
antibody-dependent cell-mediated cytotoxicity
ADE
adverse device effect
AE
adverse event
ALB
albumin
ALT
alanine aminotransferase
aPCC
activated prothrombin complex concentrate
APTT
activated partial thromboplastin time
AST
aspartate aminotransferase
ATIII
anti-thrombin III
AUC
area under the curve
AUCinf
area under the concentration time curve from time 0 to infinity
AUClast
area under the concentration time curve from time 0 to the time of 
the last quantifiable concentration
AUCt
area under the concentration-time curve from time 0 to time t, where 
t can have a numerical value
AUEC
area under the PD change from baseline time profile from time zero 
to Day 28
BID
Twice a day
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
CDC
Complement dependent cytotoxicity
CDE
Center for Drug Evaluation
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
Cmax
maximum observed concentration
CNS
central nervous systems
CL/F
apparent clearance
CO2
carbon dioxide (bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
Coronavirus Disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
clinical study report
CT
clinical trial

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Abbreviation
Term
CTCAE
Common Terminology Criteria for Adverse Events
cTnI
cardiac troponin I
CV
cardiovascular
%CV
geometric percent coefficient of variation
DILI
drug induced liver injury
DMC
data monitoring committee
dPT
dilute prothrombin time
DRE
disease-related event
EC
ethics committee
ECG
Electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FcR
Fc receptor
Fg
fibrinogen
FIH
first in human
FIP
first in patient
FVIIa
factor-activated coagulation factor VII
FIX
coagulation factor IX
FXa
activated coagulation factor IX
rFVIIa 
recombinant activated coagulation factor VII
FVIII
coagulation factor VIII
GCP
Good Clinical Practice
eGFR
Estimated glomerular filtration rate
GGT
gamma-glutamyl transferase
GLOB
globulin
GLP
Good Laboratory Practice
HbcAb
hepatitis B core antibody
HbsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
Kel
the terminal phase rate constant calculated by a linear regression of 
the loglinear concentration time curve.
K1
Kunitz domain 1
K2
Kunitz domain 2
hr
hours
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
Identification

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Abbreviation
Term
IFN-¤
Interferon gamma
IgG1
immunoglobulin G isotype, subclass 1
IMP
investigational medicinal product
IND
investigational new drug application
INR
international normalized ratio
IL-6
Interleukin-6
IP manual
investigational product manual
ISO
International Organization for Standardization
IRB
institutional review board
IV
intravenous
IVIG
IV immunoglobulin
LFT
liver function test
LLN
lower limit of normal
MaxEff
Maximum PD change from baseline
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
min
minutes
msec
millisecond
N/A
not applicable
NAb
neutralizing antibodies
NIMP
noninvestigational medicinal product
NMPA
National Medical Products Administration
NOAEL
no-observed-adverse-effect level
NSAIDs
non-steroidal anti-inflammatory drugs
PCC
prothrombin complex concentrate
PCD
primary completion date
PD
pharmacodynamic(s)
PF1+2
prothrombin fragment 1+2
PK
pharmacokinetic(s)
PT
prothrombin time
PWH
people with hemophilia
PVC
premature ventricular contraction/complex
QW
once weekly
QTc
corrected QT interval
QTcF
corrected QT interval (Fridericia method)
QoL
quality of life
QW
once weekly
RBC
red blood cell
RNA
ribonucleic acid
SADE
serious adverse device effect
SAE
serious adverse event
SAP
statistical analysis plan

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Abbreviation
Term
SARS-CoV2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous
SoA
schedule of activities
SOP
standard operating procedure
SPR
Surface Plasmon Resonance
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
t½
apparent terminal half-life
Tbili
total bilirubin
TCMs
traditional Chinese medicine
TEAE
treatment-emergent adverse events
TEG
thromboelastography
TF
tissue factor
TGA
thrombin generation assays
THC
tetrahydrocannabinol
TFPI
tissue factor pathway inhibitor
Tmax
time to reach maximum concentration
TNF¢
Tumor necrosis factor¢
TK
toxicokinetic
ULN
upper limit of normal
US
United States
WBC
white blood cell
WFH
World Federation of Hemophilia

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10.10. Appendix 10: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer.
Use of these alternative study measures are expected to cease upon the return of business as
usual circumstances (including the lifting of any quarantines and travel bans/advisories).
10.10.1. Eligibility 
While SARSCoV2 testing is not mandated for this study, local clinical practice standards for 
testing should be followed. A patient should be excluded if he/she has a positive test result 
for SARS-CoV2 infection, is known to have asymptomatic infection, or is suspected of 
having SARS-CoV2. 
10.10.2. Telehealth Visits
In the event that in-clinic study visits can not be conducted, every effort should be made to 
follow- up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare
information and services via telecommunication technologies (e.g., audio, video, video-
conferencing software) remotely,allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit:
•
Review and record any new concomitant medications or changes in concomitant 
medications since last contact. 
•
Review and record any AEs and SAEs since last contact, including but not limited to 
COVID-19 related events. The AE and SAE reporting process should be followed per 
protocol (Section 10.3, Appendix 3). 
•
Confirm that the participant is adhering to the contraception method(s) required in the 
protocol.
•
Review bleeding episodes and factor or bypass infusions. 
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
10.10.3. Alternative Facilities for Safety Assessments
10.10.3.1. Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local regulations. The 
local laboratory may be a standalone institution or within a hospital. The following safety
laboratory evaluations may be performed at a local laboratory:

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•
Hematology
•
Serum chemistry
•
APTT,PT/INR,Fg
•
Anti-thrombin III;
•
Cardiac Troponin I;
•
Urinalysis;
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/ 
accreditations for filing at the site. Laboratory test results are to be provided to the site staff as 
soon as possible. The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should be recorded on 
the CRF.
10.10.3.2. Electrocardiograms
If the participant is unable to visit the study site for ECGs, the participant may visit an alternative 
facility to have the ECGs performed. Qualified study site personnel must order, receive, and 
review results.
10.10.4. Study Intervention
If the safety of a trial participant is at risk because they cannot complete required evaluations or 
adhere to critical mitigation steps, then discontinuing that participant from study intervention 
must be considered.
10.10.5. Home Health Visits
A home health care service may be utilized to facilitate scheduled visits per the Schedule of 
Activities. Home health visits include a healthcare provider conducting an in-person study visit at 
the participant’s location, rather than an in-person study visit at the site. The following may be 
performed during a home health visit:
•
Physical exam/brief physical exam 
•
All protocol required lab draws 
•
Weight and vital signs (eg, body temperature, BP, pulse rate, respiratory rate). 
10.10.6. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an adverse event (AE) 
or serious adverse events (SAE) and appropriate medical intervention provided. It is 
recommended that the investigator discuss temporary or permanent discontinuation of study
intervention with the study medical monitor.

PF-06741086
B7841010
Final Protocol Amendment 1 22-Oct-2020
PFIZER CONFIDENTIAL
Page 101
11. REFERENCES
1.
Srivastava A, Brewer AK, Mauser-Bunschoten EP et al. Guidelines for the management of 
hemophilia. Haemophilia 2013;19: e1–47
2.
2017 Global annual survey report World Federation of Hemophilia (WFH)
3.
China Statistical Yearbook 2011
4.
Sun J et al.The demographics, treatment characteristics and quality of life of adult people 
with haemophilia in China - results from the HERO study. Haemophilia. (2017)
5.
Poon MC, Luke KH. Haemophilia care in China: achievements of a decade of World 
Federation of 
Hemophilia treatment centre twinning 
activities. Haemophilia 
2008;14(5):879-88
6.
MC Ozelo, MA Matta, R Yang Meeting the challenges of haemophilia care and patient 
support in China and Brazil Haemophilia, 2012
7.
Runhui Wu et al The benefit of low dose prophylaxis in the treatment of hemophilia: a 
focus on China Expert review of hematology 2017;10:995-1004
8.
Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 2012;379(9824):1447-56.
9.
Astermark J. Overview of inhibitors. Semin Hematol. 2006;43(2 Suppl 4):S3-7.
10. Maroney SA, Ellery PE, Wood JP, et al. Comparison of the inhibitory activities of human 
tissue 
factor 
pathway 
inhibitor 
(TFPI)alpha 
and 
TFPIbeta. 
J 
Thromb 
Haemost.2013;11(5):911-8.
11. Knappe S, Gorczyca ME, Jilma B, et al. Plasmatic tissue factor pathway inhibitor is a major 
determinant of clotting in factor VIII inhibited plasma or blood. Thromb Haemost. 
2013;109(3):450-7.
12. Dahm A, Van Hylckama Vlieg A, Bendz B, et al. Low levels of tissue factor pathway 
inhibitor (TFPI) increase the risk of venous thrombosis. Blood. 2003;101(11):4387-92.
13. Department of Health and Human Services, National Institutes of Health, National Cancer 
Institute, Common Terminology Criteria for Adverse Events. Version 5.0. 27 November 
2017

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