Clinical trial NCT03275740
Conditions: Healthy Primary Immune Thrombocytopenia Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Sponsor: Pfizer
Start date: 2017-07-17; Completion date: 2023-01-06
Enrollment: 58 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This phase 1 single ascending dose study will provide a first in human assessment of safety and tolerability of PF-06755347 in healthy adult males as well as adult males and females with Immune Thrombocytopenia (ITP). Pharmacokinetics and pharmacodynamics will also be evaluated.

Detailed description:

Arms: arm 1: intravenous administration arm 2: intravenous administration arm 3: subcutaneous administration arm 4: subcutaneous administration arm 5: subcutaneous
Interventions: intervention 1: PF-06755347 intravenous healthy participant intervention 2: Placebo intravenous healthy participant intervention 3: PF-06755347 subcutaneous healthy participant intervention 4: Placebo subcutaneous healthy participant intervention 5: PF-06755347 subcutaneous ITP
Intervention descriptions: intervention 1: Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6. intervention 2: Placebo comparator intervention 3: single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5. intervention 4: placebo comparator intervention 5: single doses of PF-06755347 will be administered subcutaneously at 2 dose levels tested in healthy participants

Protocol documents:
Prot_000.pdf: 
PF-06755347 
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Final Protocol Amendment 8, 25 July 2022
PFIZER CONFIDENTIAL
Page 1
CLINICAL PHARMACOLOGY PROTOCOL
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN,
PLACEBO -CONTROLLED, FIRST-IN-HUMAN TRIAL TO EVALUATE THE 
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF-06755347 AFTER 
SINGLE ASCENDING INTRAVENOUS AND SUBCUTANEOUS DOSING IN 
HEALTHY ADULT MALE PARTICIPANTS AND OPEN-LABEL AFTER SINGLE 
SUBCUTANEOUS DOSING IN MALE AND FEMALE PARTICIPANTS WITH 
PERSISTENT OR CHRONIC PRIMARY IMMUNE THROMBOCYTOPENIA
Investigational Product Number:
PF-06755347
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
 
European Clinical Trials Database 
(EudraCT) Number:
Protocol Number:
B7801001
Phase:
1
Short Title: A Phase 1 randomized, placebo-controlled study to evaluate safety, 
tolerability, and PK of PF-06755347 after SAD IV or SC dosing in HPs and open-label by
SC dosing in participants with persistent or chronic primary ITP.
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol Amendment Summary of Changes Table
Amendment 8 25 July 2022
Overall Rationale for the Amendment to incorporate changes requested by the Czech 
Republic Regulatory Agency, add 
 biomarker collection and clarify rescue 
medications to be consistent with BRC.  
Section # and 
Name
Description of 
Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 10.12 
Appendix 12
Country Specific 
Requirements
Added specific Czech 
Republic requirements 
to Appendix 12
Regulatory request
Substantial
Section 6.6 Dose 
Progression
Added specific Czech 
Republic enrollment 
requirements for
female participants
Regulatory request
Substantial
 
 
 
 
 
Rescue Medication 
6.5.1.1 and 6.5.1.2
Provided specific 
guidance to 
investigators regarding 
rescue therapy for 
CRS and for bleeding 
in participants with 
ITP
Regulatory request 
for clarity and RMC 
requirement
Nonsubstantial
4.2.1.3.2. 
Subcutaneous 
Administration in 
Healthy 
Participants
Table 7
Added updated values
of Observed Human 
Exposures and Safety 
Margins Following 
Single SC 
Administration of 
PF-06755347
Makes data table 
current
Nonsubstantial
Section 5.3 
Inclusion Criteria 
for Participants 
with ITP
Added references for 
the established 
guidelines for ITP
Corroborates with
the inclusion 
criterion for ITP
Nonsubstantial
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Section # and 
Name
Description of 
Change
Brief Rationale
Substantial or 
Nonsubstantial
Section 1.1 
Protocol Overview 
Cohort Overview 
for IV and SC 
Administration
Added numbers of
participants dosed
Makes data table 
current
Nonsubstantial
Section 4.1 
Overall Design
Included changes 
implemented with
PACL dated 01 Apr 
2022
To explain the 
reason that the safety 
and tolerability of 
PF-06755347 is not 
being evaluated in 
healthy female 
participants prior to 
administration to 
female participants 
with ITP in 
B7801001
Nonsubstantial
Section 10.13 
Appendix 13
Protocol 
Amendment 
History
Moved protocol 
amendment history to 
new Appendix 13
Updated per 
Sponsor’s revised 
SOP protocol 
template
Nonsubstantial
This amendment incorporates all revisions to date, including amendments made at the
request of country health authorities and IRBs/EC and any global protocol administrative 
change letter(s).


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
LIST OF FIGURES ...................................................................................................................9
SCHEDULE OF ACTIVITIES................................................................................................10
1. PROTOCOL SUMMARY...................................................................................................19
1.1. Synopsis ..................................................................................................................19
1.2. Schema ....................................................................................................................23
2. INTRODUCTION ...............................................................................................................24
2.1. Study Rationale .......................................................................................................24
2.1.1. Drug Development Rationale .....................................................................26
2.2. Background .............................................................................................................27
2.2.1. Nonclinical Pharmacology..........................................................................27
2.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................28
2.2.3. Nonclinical Safety ......................................................................................29
2.3. Benefit/Risk Assessment.........................................................................................32
3. OBJECTIVES AND ENDPOINTS.....................................................................................34
4. STUDY DESIGN.................................................................................................................34
4.1. Overall Design.........................................................................................................34
4.2. Dose Justification ....................................................................................................36
4.2.1. Human Predictions......................................................................................36
4.2.1.1. Prediction of Human Pharmacokinetics....................................36
4.2.1.2. Prediction of Human Efficacious Exposure..............................37
4.2.1.3. Clinical Dose Selection .............................................................37
4.3. End of Study Definition ..........................................................................................40
5. STUDY POPULATION......................................................................................................40
5.1. Inclusion Criteria for Healthy Participants..............................................................41
5.2. Exclusion Criteria for Healthy Participants ............................................................41
5.3. Inclusion Criteria for Participants with ITP ............................................................44
5.4. Exclusion Criteria for Participants with ITP...........................................................45
5.5. Lifestyle Considerations..........................................................................................49
5.5.1. Meals and Dietary Restrictions...................................................................49
5.5.2. Caffeine, Alcohol and Tobacco ..................................................................49


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5.5.3. Activity .......................................................................................................49
5.5.4. Contraception..............................................................................................50
5.6. Screen Failures ........................................................................................................50
6. STUDY INTERVENTION..................................................................................................50
6.1. Study Intervention(s) Administered........................................................................50
6.1.1. Administration............................................................................................51
6.1.1.1. Guideline on Intravenous Infusion............................................51
6.1.1.2. Guideline on Subcutaneous Injection........................................52
6.2. Preparation/Handling/Storage/Accountability ........................................................53
6.2.1. Preparation and Dispensing........................................................................54
6.3. Measures to minimize bias: Randomization and blinding ......................................54
6.3.1. Allocation to Investigational Product .........................................................54
6.3.2. Breaking the Blind (for HP cohorts only)...................................................55
6.4. Study Intervention Compliance...............................................................................55
6.5. Concomitant Therapy..............................................................................................56
6.5.1. Rescue Medication......................................................................................56
6.5.1.1. Rescue Therapy for CRS...........................................................56
6.5.1.2. Rescue Therapy for Bleeding Events in ITP Participants.........56
6.6. Dose Progression.....................................................................................................56
6.7. Dose Escalation.......................................................................................................58
6.8. Infusion or Injection Site Reactions (ISR) ..............................................................59
6.9. Intervention After the End of the Study..................................................................60
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................60
7.1. Participant Discontinuation/Withdrawal from the Study........................................61
7.1.1. Withdrawal of Consent...............................................................................62
7.2. Lost to Follow up ....................................................................................................62
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................63
8.1. Efficacy Assessments..............................................................................................64
8.2. Safety Assessments .................................................................................................64
8.2.1. Physical Examinations................................................................................64
8.2.2. Vital Signs ..................................................................................................64


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8.2.2.1. Respiratory Rate........................................................................65
8.2.2.2. Temperature ..............................................................................65
8.2.3. Electrocardiogram.......................................................................................65
8.2.3.1. Continuous Cardiac Monitoring by Telemetry .........................66
8.2.4. Clinical Safety Laboratory Assessments ....................................................66
8.2.5. Pulse Oximetry ...........................................................................................67
8.2.6. Pregnancy Testing ......................................................................................67
8.3. Adverse Events and Serious Adverse Events..........................................................67
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......68
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................68
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF .................68
8.3.2. Method of Detecting AEs and SAEs ..........................................................69
8.3.3. Follow-up of AEs and SAEs.......................................................................69
8.3.4. Regulatory Reporting Requirements for SAEs...........................................69
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................70
8.3.5.1. Exposure During Pregnancy......................................................70
8.3.5.2. Exposure During Breastfeeding ................................................71
8.3.5.3. Occupational Exposure .............................................................72
8.3.6. Cardiovascular and Death Events...............................................................72
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................72
8.3.8. Adverse Events of Special Interest.............................................................72
8.3.8.1. Lack of Efficacy........................................................................72
8.3.9. Medical Device Deficiencies......................................................................72
8.3.10. Medication Errors.....................................................................................72
8.4. Treatment of Overdose............................................................................................73
8.5. Pharmacokinetics ....................................................................................................74
8.5.1. Analysis of PF-06755347 ...........................................................................74
8.5.2. Analysis of Anti-Drug Antibodies..............................................................74
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9. STATISTICAL CONSIDERATIONS ................................................................................78
9.1. Statistical Hypotheses .............................................................................................78
9.2. Sample Size Determination.....................................................................................78
9.3. Populations for Analysis .........................................................................................79
9.4. Statistical Analyses .................................................................................................79
9.4.1. Efficacy Analyses .......................................................................................79
9.5. Pharmacokinetic Analysis.......................................................................................79
9.5.1. Derivation of Pharmacokinetic Parameters ................................................79
9.5.1.1. Statistical Methods ....................................................................81
9.7. Analysis of Other Endpoints ...................................................................................81
9.8. Safety Analysis........................................................................................................81
9.8.1. Electrocardiogram Analysis........................................................................82
9.9. Interim Analysis ......................................................................................................82
9.10. Data Monitoring Committee .................................................................................83
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................84
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............84
10.1.1. Regulatory and Ethical Considerations ....................................................84
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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................84
10.1.2. Informed Consent Process ........................................................................85
10.1.3. Data Protection .........................................................................................86
10.1.4. Dissemination of Clinical Study Data ......................................................86
10.1.5. Data Quality Assurance ............................................................................88
10.1.6. Source Documents....................................................................................89
10.1.7. Study and Site Closure..............................................................................89
10.1.8. Publication Policy.....................................................................................90
10.1.9. Sponsors Qualified Medical Personnel.....................................................90
10.2. Appendix 2: Clinical Laboratory Tests .................................................................92
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................94
10.3.1. Definition of AE .......................................................................................94
10.3.2. Definition of SAE.....................................................................................96
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................97
10.3.4. Reporting of SAEs..................................................................................100
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..............................................................................................................101
10.4.1. Male Participant Reproductive Inclusion Criteria..................................101
10.4.2. Female Participant Reproductive Inclusion Criteria...............................101
10.4.3. Woman of Childbearing Potential ..........................................................102
10.4.4. Contraception Methods...........................................................................103
10.5. Appendix 5: Genetics..........................................................................................106
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......107
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................109
10.8. Appendix 8: Alternative Measures During Public Emergencies ........................111
10.8.1. Eligibility................................................................................................111
10.8.2. Telehealth Visits.....................................................................................111
10.8.2.1. Laboratory Testing ................................................................112
10.8.2.2. Electrocardiograms................................................................112
10.8.3. Adverse Events and Serious Adverse Events.........................................112


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10.9. Appendix 9: Grading System for Pro-Inflammatory-Related Adverse 
Events ......................................................................................................................113
10.10. Appendix 10: CRS Grading System and Management.....................................114
10.11. Appendix 11: CTCAE (version 4.03) Grading System for 
Infusion-Related Reactions .....................................................................................116
10.12. Appendix 12: Country Specific Requirements..................................................117
10.12.1. Czech Republic.....................................................................................117
10.13. Appendix 13 Protocol Amendment History......................................................121
10.14. Appendix 14: Abbreviations .............................................................................135
11. REFERENCES ................................................................................................................139
LIST OF TABLES
Table 1.
Schedule of Activities for IV cohorts.......................................................10
Table 2.
Schedule of Activities for SC Cohorts of Healthy Participants................13
Table 3.
Schedule of Activities for SC Cohorts of ITP Participants ......................16
Table 4.
Cohort Overview for IV and SC Administration......................................20
Table 5.
In Vitro PF-06755347 Potency for Increases in Cytokines and 
Complement Component..........................................................................29
Table 6.
Observed Human Exposure and Safety Margin Following Single IV 
Administration of PF-06755347...............................................................37
Table 7.
Observed/Predicted Human Exposures and Safety Margins 
Following Single SC Administration of PF 06755347.............................40
Table 8.
Guideline on Intravenous Infusion Scheme..............................................52
Table 9.
Total Blood Sample Volume ....................................................................78
Table 10.
Plasma Pharmacokinetic Parameter Definition ........................................80
Table 11.
Categories for Safety QTcF......................................................................82
Table 12.
Safety Laboratory Tests............................................................................92
Table 13.
ASTCT CRS Revised Grading System12................................................114
Table 14.
Schedule of Activities for SC Cohorts of ITP Participants- Czech 
Republic ONLY......................................................................................117
LIST OF FIGURES
Figure 1.
Study Schematic .......................................................................................23


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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES of the protocol for detailed information on each procedure and assessment required for compliance with the protocol.  The 
investigator may schedule visits (unplanned visits) in addition to those listed in the schedule of activities table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Table 1.
Schedule of Activities for IV cohorts
Protocol Activity
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
Abbreviations used in this table may 
be found in 10.14. Appendix 14: 
Abbreviations
-56 to 
-2
-1a
1
2
3
4
6
8
11
±2
15
±2
22
±2
29
±2
36a
±3
50a
±3
71a
±3 or 
ET
Hour(s) Post Dose 
0
pre-dose
0.5
1 or 
EOIb
3 or 
EOIc
3.5
4
5 
6
8
12
24
36
48 72 120 168 240 336 504 672 840 1176 1680
Informed consent
X
Demography (including Height)
X
Outpatient Visit
X
X
X
X
X
Xa
Xa
Xa
Study Site Confinement
X













X
Discharge
X
Chest X-rayd
X
QuantiFERON-TB Gold test
X
HIV, HepBsAg, HepBcAb, HCVAb 
tests
X
Test for anti-cardiolipin antibody, 
rheumatoid factor, anti-nuclear 
antibody, Total IgG and Total IgA, 
TSH, thyroxine (free T4), and 
triiodothyronine (free T3) and TSAb. 
Lipid profile.  
X
Inclusion/Exclusion
X
X
Medical history; history of illegal 
drug, alcohol & tobacco use
X
Xe
Medication history
X
Xe
Weight
X
X
Xf
Xf
Urine drug screening
X
X
Review contraception use
X
X
X
X
X
X
X
X
X
X
Physical examinationg
X
X
X
X
X
X
X
X
X
X


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Table 1.
Schedule of Activities for IV cohorts
Protocol Activity
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
Abbreviations used in this table may 
be found in 10.14. Appendix 14: 
Abbreviations
-56 to 
-2
-1a
1
2
3
4
6
8
11
±2
15
±2
22
±2
29
±2
36a
±3
50a
±3
71a
±3 or 
ET
Hour(s) Post Dose 
0
pre-dose
0.5
1 or 
EOIb
3 or 
EOIc
3.5
4
5 
6
8
12
24
36
48 72 120 168 240 336 504 672 840 1176 1680
Hematology & Coagulation (PT, 
INR, PTT, D-dimer & fibrinogen) 
Safety Labs
X
X
Xm,n
Xn
Xn
Xn
Xn
X
Xn
X
X
X
X
X
X
X
X
X
X
Chemistry/Urinalysis/Other Safety 
Labs
X
X
Xm,n
X
X
X
X
X
X
X
X
X
X
X
ECGh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Telemetry
Xi
Xi







X
Vital signs (BP, pulse rate, 
temperature)j
X
X
X
X
X
Xn
Xn
X
Xn
X
X
X
X
X
X
X
X
X
X
X
Xn
X
Xn
X
Pulse Oximetry
X
X
X
X
X
Xn
Xn
X
Xn
X
X
X
X
X
X
X
X
X
X
X
Xn
X
Xn
X
ADA blood sampling
Xo
X
X
X
X
X
 
 
IV administration
Xl

X
X
Infusion site assessment
X
X
X
X
Xn
Xn
X
Xn
X
X
X
Xn
Xn
Xn
Xn
PK blood sampling (IV Cohorts 1 
and 2 only)
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling (IV Cohorts 3-5)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling (IV Cohorts 5 
exp. 6-9, and optional IV cohorts)
X
Xm,n
X
Xn
Xn
X
Xn
X
X
X
X
X
X
X
X
X
X
X
X
X
Serious and non-serious Adverse 
Event monitoring
X
X




















X
Prior/Concomitant treatments
X
X
X
X










X
Abbreviations: = ongoing/continuous; ADA= anti-drug antibody; BP = blood pressure; ECG = electrocardiogram; EOI = end of infusion; HepBsAg = hepatitis B surface 
antigen; HepBcAb = hepatitis B core antibody; HCVAb = hepatitis C antibody; HIV = human immunodeficiency virus; IgA = immunoglobulin A; IgG = immunoglobulin G; 
INR = international normalized ratio; IV = intravenous; PK = pharmacokinetics; PT = prothrombin time; PTT = partial thromboplastin time; RNA = ribonucleic acid; 
TB = tuberculosis; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; TSAb = thyroid stimulating antibodies.
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a.
Admission may be on Day -2 or Day -1 at the discretion of the Investigator.  Cohorts with proposed doses ≤1 mg/kg by intravenous (IV) administration will 
complete the study on approximately Day 36.  Remaining visit(s)/assessments are not applicable if participant has completed the study.  Cohorts with 
proposed doses >1 mg/kg by IV administration will complete the study at approximately Day 71.  If a participant discontinues early they should, when 
possible, return to complete assessments outlined at Day 71.  The follow-up period may be extended if any participant in a particular cohort is tested positive 
for anti-drug antibody to PF-06755347 or has detectable concentration of PF-06755347 at final study visit.  If there is an early termination (ET), the Day 71 
schedule will be followed.
b.
Immediately prior to end of infusion (PEOI) for cohorts with targeted infusion duration of approximately 1 hour.  If the infusion is interrupted and restarted, 
the infusion duration will not exceed 2 hours.
c.
Immediately prior to end of infusion (PEOI for cohorts with targeted infusion duration of 3 hours. If the infusion is interrupted, the infusion duration will 
not exceed 4 hours.
d.
Chest X-ray results within 3 months of screening visit otherwise a chest X-ray must be performed at screening and results obtained prior to admission. 
e.
Update alcohol and nicotine use since screening.
f.
Weight should be measured at Day 36 for participants on a dose of ≤1 mg/kg and on Day 71 only for participants on a dose of >1 mg/kg.
g.
Full physical examination (PE) may be done at screening or may be deferred to admission at the discretion of the investigator.  If a full PE is performed at 
screening, a limited PE may be performed at admission.  Limited PE may be performed at discharge or at any outpatient visit at the discretion of the 
investigator.
h.
Single electrocardiogram (ECG) at screening and scheduled outpatient visits; triplicate ECG at all other time points (including unscheduled, early 
termination, or extended immune follow-up visit). 
i.
Baseline for at least 2 hours between admission and prior to dosing while awake. 
j.
Vital signs measurement (including BP, pulse rate & temperature) triplicate at pre-dose only, at the discretion of the investigator triplicate assessments may 
be taken at other timepoints. Oral or tympanic method for temperature determination is allowed, however must be used consistently for each participant.
k.
Banked biospecimen may be collected on admission or Day 1 (prior to dosing). If not collected on the designated collection day, collect at the next available 
time point when biospecimens are being collected in conjunction with a participant visit. 
l.
Start of infusion time.
m. Samples for safety laboratory and pharmacokinetics (PK) at 1 h will not be collected in participants with targeted infusion duration ≥3 h. 
n.
Procedures updated from amendment 2.
o.
No screening anti-drug antibody (ADA) blood sample is needed for participants in Cohort 5 expansion and in Cohorts 6-11.


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Table 2.
Schedule of Activities for SC Cohorts of Healthy Participants 
Protocol Activity
Abbreviations used in this table may be 
found in 10.14. Appendix 14: 
Abbreviations
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or 
ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5
6
8
12
24
36 48
72
96
120 168 240 336 504 672 840 1176 1680
Informed consent
X
Demography (including Height)
X
Outpatient Visit
X
X
X
X
X
X
X
X
Study Site Confinement
X















X
Randomization
X
Discharge
X
Chest X-rayb
X
QuantiFERON-TB Gold test
X
HIV, HepBsAg, HepBcAb, HCVAb 
tests
X
Test for rheumatoid factor, anti-nuclear 
antibody, Total IgG and Total IgA, 
TSH, thyroxine (free T4), and 
triiodothyronine (free T3) TSAb; Lipid 
profile.  
X
Inclusion/Exclusion
X
X
Medical history; history of illegal drug, 
alcohol & tobacco use
X
Xc
Medication history
X
Xc
Weight
X
X
X
X
Urine drug screening
X
X
Review contraception use
X
X
X
X
X
X
X
X
X
X
Physical examinationd
X
X
X
X
X
X
X
X
X
X
Hematology & Coagulation (PT, INR, 
PTT, D-dimer & fibrinogen) Safety 
Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry/Urinalysis/Other Safety 
Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECGe
X
X
X
X
X
X
X
X
X
X
X
X
X
Telemetryh
X
X







X


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Table 2.
Schedule of Activities for SC Cohorts of Healthy Participants 
Protocol Activity
Abbreviations used in this table may be 
found in 10.14. Appendix 14: 
Abbreviations
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or 
ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5
6
8
12
24
36 48
72
96
120 168 240 336 504 672 840 1176 1680
Vital signs (BP, pulse rate, 
temperature)f
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
Pulse Oximetry
X
X
X
X
X
X
X
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
ADA blood sampling
X
X
X
Xi
X
 
 
SC Administration
X
SC Injection site assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling (SC cohorts)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serious and non-serious Adverse Event 
monitoring
X
X






















X
Prior/Concomitant treatments
X
X
X
X












X
Abbreviations: = ongoing/continuous; ADA= anti-drug antibody; BP = blood pressure; ECG = electrocardiogram; EOI = end of infusion; HepBsAg = hepatitis B surface 
antigen; HepBcAb = hepatitis B core antibody; HCVAb = hepatitis C antibody; HIV = human immunodeficiency virus; IgA = immunoglobulin A; IgG = immunoglobulin G; 
INR = international normalized ratio; PK = pharmacokinetics; PT = prothrombin time; PTT = partial thromboplastin time; RNA = ribonucleic acid; SC = subcutaneous; 
TB = tuberculosis; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; TSAb = thyroid stimulating antibodies.
a.
Admission may be on Day -2 or Day -1 at the discretion of the Investigator. If a participant discontinues early they should, when possible, return to 
complete assessments outlined at Day 71. The follow up period may be extended if any participant in a particular cohort is tested positive for anti-drug
antibody to PF-06755347 or has detectable concentration of PF-06755347 at final study visit.  If there is an early termination (ET), the Day 71 schedule will 
be followed.
b.
Chest X-ray results within 3 months of screening visit otherwise a chest X-ray must be performed at screening and results obtained prior to admission. 
c.
Update alcohol and nicotine use since screening. 
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d.
Full physical examination (PE) may be done at screening or may be deferred to admission at the discretion of the investigator.  If a full PE is performed at 
screening, a limited PE may be performed at admission.  Limited PE may be performed at discharge or at any outpatient visit at the discretion of the 
investigator.
e.
Single electrocardiogram (ECG) at screening and scheduled outpatient visits; triplicate ECG at all other time points (including unscheduled, early 
termination, or extended immune follow up visit). 
f.
Vital signs measurement (including BP, pulse rate & temperature) triplicate at pre dose only, at the discretion of the investigator triplicate assessments may 
be taken at other timepoints. Either oral or tympanic method for temperature determination is allowed; however the method should be used consistently for 
each participant.
g.
Banked biospecimen may be collected on admission or Day 1 (prior to dosing).  If not collected on the designated collection day, collect at the next available 
time point when biospecimens are being collected in conjunction with a participant visit.
h.
Only participants dosed prior to acceptance of protocol amendment 6 will have telemetry performed.


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Table 3.
Schedule of Activities for SC Cohorts of ITP Participants 
Protocol Activity
Abbreviations used in this table may be 
found in 10.14. Appendix 14: 
Abbreviations
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or 
ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5 
6
8
12
24
36 48
72
96
120 168 240 336 504 672 840 1176 1680
Informed consent
X
Demography (including Height)
X
Outpatient Visit
X
X
X
X
X
X
X
X
Study Site Confinement
X















X
Randomization
X
Discharge
X
Chest X-rayb
X
QuantiFERON-TB Gold test
X
HIV, HepBsAg, HepBcAb, HCVAb 
tests
X
Test for rheumatoid factor, anti nuclear 
antibody, Total IgG and Total IgA, 
TSH, thyroxine (free T4), and 
triiodothyronine (free T3) TSAb; 
Lipid profile
X
Inclusion/Exclusion
X
X
Medical history; history of illegal drug, 
alcohol & tobacco use
X
Xc
Medication history
X
Xc
Weight
X
X
X
X
Urine drug screening
X
X
FSHh
X
Serum Pregnancyi
X
X
Review contraception use
X
X
X
X
X
X
X
X
X
X
Physical examinationd
X
X
X
X
X
X
X
X
X
X
Hematology & Coagulation (PT, INR, 
PTT, D-dimer & fibrinogen) Safety 
Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry/Urinalysis/Other Safety 
Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Table 3.
Schedule of Activities for SC Cohorts of ITP Participants 
Protocol Activity
Abbreviations used in this table may be 
found in 10.14. Appendix 14: 
Abbreviations
Screen
Clinical Confinement
Outpatient Follow-Up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or 
ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5 
6
8
12
24
36 48
72
96
120 168 240 336 504 672 840 1176 1680
ECGe
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP, pulse rate, 
temperature)f
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
Pulse Oximetry
X
X
X
X
X
X
X
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
ADA blood sampling
X
X
X
X
X
 
 
SC Administration
X
SC Injection site assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testj
X
X
X
Serious and non-serious Adverse Event 
monitoring
X
X






















X
Prior/Concomitant treatments
X
X
X
X












X
Abbreviations: = ongoing/continuous; ADA= anti-drug antibody; BP = blood pressure; ECG = electrocardiogram; HepBsAg = hepatitis B surface antigen; HepBcAb = hepatitis 
B core antibody; HCVAb = hepatitis C antibody; HIV = human immunodeficiency virus; IgA = immunoglobulin A; IgG = immunoglobulin G; INR = international normalized 
ratio; PK = pharmacokinetics; PT = prothrombin time; PTT = partial thromboplastin time; RNA = ribonucleic acid; SC = subcutaneous; TB = tuberculosis; T3 = triiodothyronine; 
T4 = thyroxine; TSH = thyroid stimulating hormone; TSAb = thyroid stimulating antibodies.
a.
Admission may be on Day -2 or Day -1 at the discretion of the Investigator.  If a participant discontinues early they should, when possible, return to complete assessments 
outlined at Day 71.  The follow-up period may be extended if any participant in a particular cohort is tested positive for anti-drug antibody to PF-06755347 or has detectable 
concentration of PF-06755347 at final study visit.  If there is an ET, the Day 71 schedule will be followed.
b.
Chest X-ray results within 3 months of screening visit otherwise a chest X-ray must be performed at screening and results obtained prior to admission. 
c.
Update medication history, alcohol and nicotine use since screening. 
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d.
Full PE may be done at screening or may be deferred to admission at the discretion of the investigator.  If a full PE is performed at screening, a limited PE may be performed 
at admission.  Limited PE may be performed at discharge or at any outpatient visit at the discretion of the investigator.
e.
Single ECG at screening and scheduled outpatient visits; triplicate ECG at all other time points (including unscheduled, early termination, or extended immune follow up 
visit). 
f.
Vital signs measurement (including BP, pulse rate & temperature) triplicate at pre dose only, at the discretion of the investigator triplicate assessments may be taken at other 
timepoints.  Either oral or tympanic method for temperature determination is allowed; however the method should be used consistently for each participant.
g.
Banked biospecimen may be collected on admission or Day 1 (prior to dosing).  If not collected on the designated collection day, collect at the next available time point when 
biospecimens are being collected in conjunction with a participant visit.
h.
Serum FSH will be performed to confirm postmenopausal status for females (at the investigator’s discretion whether to confirm post-menopausal status by FSH if greater than 
5 years since last menses.
i.
Serum pregnancy test will be conducted at a local lab. For female participants of childbearing potential, 2 negative pregnancy tests are required prior to dose on Day 1 (1 
negative serum pregnancy test at Screening and 1 negative urine pregnancy test on Day 1). Results of serum pregnancy test from Day -1 are not required prior to dosing.
j.
Urine pregnancy test will be conducted locally in females of ITP cohorts.


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1. PROTOCOL SUMMARY 
1.1. Synopsis
Short Title: A Phase 1 randomized, placebo controlled study to evaluate safety, tolerability, 
and PK of PF-06755347 after SAD IV or SC dosing in HPs and open-label by SC dosing in 
participants with persistent or chronic primary ITP.
Rationale
PF-06755347 is a fusion protein comprised of a recombinant human IgG1 Fc and IgG2 
hinge. The investigational product is designed to form Fc multimers in order to enhance 
avidity to low avidity Fcγ receptors and C1q. It is being developed for the treatment of 
primary immune thrombocytopenia (ITP), chronic inflammatory demyelinating 
polyneuropathy (CIDP) and rare autoimmune diseases that respond to human 
immunoglobulin.
The purpose of this first in human study is to evaluate the safety, tolerability, PK and 
potentially PD of PF-06755347 following dosing by single IV infusion and SC injection in
healthy adult male participants and by SC injection in adult male or female participants with 
persistent or chronic primary ITP.
Objectives and Endpoints
Primary Objective: 
Primary Endpoints: 

To evaluate safety and tolerability following a
single dose of PF-06755347 in the study 
population. 

Assessment of adverse events (AEs), clinical 
laboratory tests, vital signs, body temperature, 
cardiac telemetry (where collected) and 
12-lead electrocardiogram (ECG). 
Secondary Objective: 
Secondary Endpoints: 

To characterize the plasma PK profile following a 
single dose of PF-06755347 in the study 
population.

PK parameters derived from plasma 
PF-06755347 concentration: 
Cmax, Tmax, AUClast, t½, if data permit.

To evaluate the immunogenicity profile following 
a single dose of PF-06755347 in the study 
population. 

Incidence of the development of antidrug 
antibody to PF-06755347.

 
 
  
. 
Tertiary Objective: 
Tertiary Endpoints: 

To further characterize the plasma PK profile 
following a single dose of PF-06755347 in the 
study population.

PK parameters derived from plasma 
PF-06755347 concentration: 
Cmax (dn), AUClast (dn), AUCinf (dn), CL, Vss, 
CL/F, and Vz/F, if applicable.

 
 

Collection of biospecimens unless prohibited 
by local regulations or ethics committee 
decision.  Additional information on collection 
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and potential use is provided in the 
Biospecimens section.
Overall Design
This is a Phase 1, randomized, double-blind, Sponsor-open, placebo-controlled,
first-in-human SAD study to evaluate the safety, tolerability, and PK of PF-06755347 in 
healthy adult male participants by IV and SC administration and in adult male or female 
participants with persistent or chronic primary ITP by SC administration.
A schematic of the overall study design is provided in Figure 1.
A total of approximately 75 healthy adult male participants are planned to be randomized to 
either receive PF-06755347 or placebo by IV or SC administration in a 3:1 allocation ratio. 
Emerging clinical data from the IV cohorts supporting the transition to SC dosing are 
summarized in the IB, Section 6. The cohorts planned in this study are listed in Table 4. If 
cohort numbers are expanded, then the total number of participants randomized will not 
exceed 87.
Table 4.
Cohort Overview for IV and SC Administration
Cohort
Population
Optional
Number of 
Participants Dosed
SC Administration
Number of 
Participants Planned
1 - 4
HP
16
5
HP
4
6
HP
5
7
HP
4
8
HP
8
9
HP
8
10
HP
X
In progress
8
11
HP
X
ND
8
12
Japanese
X
ND
4 - 8
13
ITP
ND
3 - 6
14
ITP
ND
3 - 6
For all cohorts, participants will be dosed sequentially, with a minimum of 72-hour safety 
data (96-hour for SC administration) for each participant being reviewed by the team before 
dosing the next participant.  There will be a minimum interval of 96-hours for IV 
administration or 120-hours for SC administration between dosing of consecutive 
participants. Screening evaluation will occur within 56 days prior to dosing.  Eligible 
participants who meet the entry criteria will be admitted on Day -1 and are required to stay 
overnight through completion of Day 8 evaluations.  At the discretion of the study site,
participants may be admitted on Day -2. Participants will return for outpatient visits through 
approximately Day 36 (≤1 mg/kg IV dose level) or Day 71 (>1 mg/kg IV dose level and all 


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Page 21
subcutaneous dose levels) for a total of approximately 5 or 10 weeks study participation, 
respectively from first dose to follow-up, excluding screening.  
Dose Escalation and Study Stopping
Clinical tolerability, safety, PK
data will be reviewed 
by a dose escalation subteam to establish whether each dose level is considered safe and well 
tolerated. These criteria may lead to a pause to evaluate participants at a given dose level, to 
repeat a dose, or to dose escalation. Unless a specific pause criterion is met, a review of all 
available safety, PK, cytokine and complement data will occur after each cohort has 
completed and dose escalation will proceed if the last dose was considered to be well 
tolerated. In the event of dosing pause, all available safety, cytokine, and complement data 
for the participants will be reviewed by the dose escalation subteam. The subteam should 
determine whether clinical signs and symptoms, including laboratory findings, associated 
with the pause criteria have resolved and whether it is safe to continue dosing.
Data Monitoring Committee:
This study will not use an external data monitoring committee.  However, the dose escalation 
subteam will include an external Sponsor-independent safety reviewer.
Statistical Methods
No formal inferential statistics will be applied to the pharmacokinetic data.
The plasma concentration of PF-06755347 will be listed and summarized descriptively by 
nominal PK sampling time and treatment group.  Individual participant, mean and median 
profiles of the plasma concentration time data will be plotted by treatment group using actual 
and nominal times, respectively.  Mean and median profiles will be presented on both linear 
and log scales. 
Baseline and change from baseline in cytokines and complement components will be 
summarized descriptively and plotted by dose.
Platelet counts for participants in the ITP Cohorts will be listed and summarized
descriptively as absolute values and change from baseline.  
Immunogenicity (anti-drug antibody [ADA]) results will be listed (including titers) and 
summarized by treatment group and time points. Participant level immune response will also 
be summarized by treatment. Effect of positive ADA on safety, PD and PK will be assessed, 
if appropriate.
 
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Adverse events, ECGs, blood pressure (BP), and pulse rate, continuous cardiac monitoring 
by telemetry, and safety laboratory data will be reviewed and summarized on an ongoing 
basis during the study to evaluate the safety of participants.  Any clinical laboratory, ECG, 
BP, and pulse rate abnormalities of potential clinical concern will be described.  Safety data 
will be presented in tabular and/or graphical format and summarized descriptively, where 
appropriate.


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1.2. Schema
Figure 1.
Study Schematic
Within cohort sequential dosing scheme for IV and SC:
For all cohorts, participants will be dosed sequentially, one at a time.  A safety review of the 
post-dose 72-hour data (96-hour for SC) will occur for each participant in order to proceed 
with dosing the next participant. There will be a minimum of 96-hours (120-hours for SC 
administration) between dosing of consecutive participants.
Actual dose levels are subject to change. See Section 4.2.
Cohort 9 (N=8)
Dose 100 mg
Optional Cohort 10 
Dose 200 mg (N=8)
Cohort 7 (N=4)
Dose 25 mg 
Cohort 2 (N=4)
0.03 mg/kg
Cohort 3 (N=4)
0.1 mg/kg
Cohort 4 (N=4)
0.3 mg/kg
Cohort 5 (N=7)
1 mg/kg
Cohort 6 (N=8)
0.7 mg/kg
Subcutaneous Cohorts
(to be completed after IV Cohorts)
Cohort 1 (N=4)
0.01 mg/kg
Cohort 8 (N=8) 
Dose 50 mg
Optional Cohort 11 
Dose 300 mg (N=8)
Optional Cohort 12 
Japanese
(N, no greater than 8)
Intravenous Cohorts
Healthy Participants
Cohort 14 (N=3-6)
Dose 2 
Cohort 13 (N=3-6)
Dose 1 
Participants with ITP
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2. INTRODUCTION
PF-06755347 is a recombinant human IgG1 Fc fusion protein comprised of a recombinant 
human IgG1 Fc and IgG2 hinge. The drug candidate is designed to form multimers in order 
to enhance avidity to Fcg receptors and C1q. PF-06755347 is being developed as a treatment 
for primary ITP, CIDP, and rare autoimmune diseases that respond to human 
immunoglobulin.
2.1. Study Rationale
The current study is the first clinical trial with PF-06755347.  It is designed to evaluate the 
safety, tolerability, PK and 
 following IV infusion and SC 
injection to healthy adult male participants and SC injection in adult male or female 
participants with persistent or chronic primary ITP.  
Platelet count response in ITP is a robust, objective, validated biomarker for efficacy for 
IVIg.  An increase in platelet count would be informative for the clinical development of 
PF-06755347 in ITP and CIDP. Participants with persistent and chronic primary ITP are 
chosen to ensure a low likelihood of spontaneous resolution of the platelet count.  
Participants with moderate to severe ITP (30 – 75 x 109 platelet count) who have no acute 
need for therapy are selected to minimize undue risk to the participant (see IB,
Section 6.2.1.1), including bleeding at the injection site.
PF-06755347 modulates the production of pro- and anti-inflammatory cytokines and the 
production of complement activation products in vitro and in nonclinical species.  A 
maximum tolerated dose of 0.3 mg/kg by intravenous infusion has been identified, with 
Grades 1 and 2 CRS observed at higher doses of 0.7 and 1 mg/kg. No further IV dosing will 
occur. (see Investigator Brochure Section 6.2).  Moving forward, the safety, tolerability, and 
PK of PF-06755347 will be assessed following SC administration. 
In ITP, bleeding may occur due to low numbers of platelets, circulating cell fragments that 
clump together to form plugs in blood vessel injuries.  
The study design with single escalating IV and SC doses of PF-06755347 is ongoing with 
review of safety, PK and
.  To permit an unbiased assessment 
of safety, the administration of active PF-06755347 versus placebo in each healthy 
participant cohort will be double-blinded to site staff (except those involved in preparation of 
doses) and participants.  All participants in the ITP cohorts will receive PF-06755347.  To 
allow for real-time review of the safety, tolerability, PK and cytokine/complement data, a 
designated limited number of Sponsor colleagues will be unblinded, with careful measures 
exercised to limit degree of unblinding. Refer to Section 9.9 for details.  An independent and 
medically qualified reviewer, external to Sponsor and with authority to pause dose escalation 
to the subsequent cohort, will also be included as an unblinded member of the 
dose-escalation subteam.
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This study includes rigorous in-clinic monitoring of study participants.  Safety labs, 
urinalysis, telemetry (for participants prior to amendment 6), thorough ECG and vital sign 
assessments and adverse event monitoring will provide data to evaluate the safety and 
tolerability of PF-06755347.  A sequential dosing design (see Section 4.1), will be used for 
all participants. This design ensures no concurrent dosing of multiple participants at a given 
dose level before a sufficient amount of safety information for a given dose level is acquired. 
In total there will be a minimum of 96 hours for IV administration between each participant 
to allow for review of 72-hr safety data and a minimum of 120 hours for SC administration to 
allow for review of 96-hour safety data. In addition, the proposed dose progression and 
escalation rules (see Section 6.6 and Section 6.7) will minimize the risk to study participants 
and ensure close and controlled safety, tolerability and PK monitoring in advance of 
escalating the dose level. Blood samples will also be analyzed for anti-drug antibodies
following administration of PF-06755347.
The study will specifically screen and exclude potential participants with evidence of latent 
infections (eg, with chest X-rays and -QuantiFERON-TB Gold test for TB, HIV and 
hepatitis) to minimize the potential risk of infection even though there is no evidence of 
treatment related infections in nonclinical studies, or from the proposed immune-modulatory 
effect of PF-06755347. Additionally, given the rare thromboembolic events associated with 
intravenous (IVIg) and subcutaneous immunoglobulin (SCIg) treatment, lipid profiling (total 
cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL], triglycerides 
[TG], and apolipoprotein B100 [ApoB100]) will be conducted to exclude the participants 
who may be at higher risk of an event. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2.1.1. Drug Development Rationale 
PF-06755347 is being developed for the treatment of rare autoimmune diseases, specifically
primary ITP and CIDP.1,8,9 Primary ITP is characterized by a peripheral blood platelet count 
of <100 × 109/L in the absence of another cause/disorder to explain the deficit. The main 
clinical concern is an increased risk of bleeding due to insufficient numbers of platelets, 
circulating cell fragments that clump together to form plugs in blood vessel injuries. CIDP is 
a rare polyneuropathy typically affecting both motor and sensory nerves. Plasma derived 
IVIg is an approved therapy for both of these indications. Similar to IVIg, the therapeutic 
goal of the PF-06755347 program is to increase platelet levels in ITP patients, and to 
improve the balance of pro- and anti-inflammatory factors involved in autoimmunity and 
inflammation that occur in CIDP patients.
PF-06755347 has been demonstrated to have enhanced potency compared to IVIg in multiple
preclinical autoimmune disease models. These data suggested that lower doses of
PF-06755347 may be sufficient for efficacy in autoimmune disease patients, enabling lower
administration volumes and shorter administration times compared to those required for 
IVIg.
It has been shown that the Fc component of IVIg preparations is primarily responsible for the 
therapeutic activity of IVIg in several autoimmune disease models. IVIg preparations in 
which the Fab component was removed demonstrated similar efficacy to whole IVIg in the 
passive idiopathic thrombocytopenic purpura (ITP) model in mice,2 and in the rat 
experimental autoimmune neuritis (EAN) model of CIDP.3  In clinical ITP studies, it has 
been shown that the Fc component of IVIg rescued platelet numbers, similar to that seen with 
unmodified IVIg preparations.14  There are multiple potential mechanistic pathways 
involving discrete Fc receptors and different cell types that may contribute to the anti-
inflammatory and immune-modulatory activities of the Fc portion of IVIg. However it is not 
currently possible to identify a single molecular and cellular pathway that is responsible for 
clinical efficacy.2
PF-06755347 is a recombinant human IgG1 multimeric Fc fusion protein that is being 
developed for the treatment of autoimmune disorders currently treated with IVIg, including 
ITP and CIDP.  It is designed to form a drug product comprising multimerized Fc species
(including the homodimer) which display enhanced avidity to Fc receptors.  The multimeric 
structure of PF-06755347 is hypothesized to reproduce the functional activity of high
molecular weight Fc containing immune aggregates in IVIg for the treatment of various 
autoimmune diseases.  Internal studies demonstrated that multimerization drives a 2-3 order 
of magnitude greater avidity for the FcRs than IVIg and increased potency has been 
demonstrated in several cell-based assays of FcR activation and immune cell functional 
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activity.  PF-06755347 and its murine analogue M045, demonstrated efficacy in several 
independent autoimmune disease animal models including those for CIDP, ITP, rheumatoid 
arthritis, and myasthenia gravis.  In studies where a direct comparison was done with human 
IVIg, the recombinant material was similarly effective at a 25-fold lower dose. The proposed 
mechanism of action of PF-06755347, the Fc-dependent efficacy of IVIg in autoimmune 
diseases, and the PF-06755347 driven efficacy in autoimmune disease rodent models at doses 
significantly lower than IVIg together suggest a utility for PF-06755347 in the treatment of 
rare autoimmune diseases such as ITP and CIDP.
2.2. Background
2.2.1. Nonclinical Pharmacology 
PF-06755347 demonstrated high binding avidity (apparent Kd ≤1.45E-10 M) to a panel of 
available recombinant human FcRs.  These binding avidity values were 2-3 orders of 
magnitude lower than that seen with IVIg for all FcRs except for the high avidity receptor, 
FcRI.  Similar, but lower (compared to FcRs) binding to the neonatal Fc receptor (FcRN)
was observed with PF-06755347 and IVIg (Kd ≤3.61E-05 M).  PF-06755347 bound with high 
avidity to available recombinant human, cynomolgus monkey, rat and mouse FcRs, 
providing rationale for further studies in rodent and monkey efficacy and toxicology studies.
The consequence of PF-06755347 binding to these receptors was demonstrated by its 
inhibition of immune complex binding to Chinese Hamster Ovary (CHO) cells engineered to 
express FcRs and its inhibition of FcR-mediated macrophage phagocytosis of 
antibody-opsonized immune cells.  Also, PF-06755347 induced signaling downstream of 
ligand binding to human FcRIIA and FcRIIIA receptors on Jurkat cells in a reporter assay.  
In primary human blood-derived neutrophil preparations, PF-06755347 inhibited neutrophil 
chemotaxis induced by C5a with a mean IC50 in the range of 0.2-1 µg/mL, and inhibited 
neutrophil transendothelial migration induced by IL-8 with a mean IC50 in the range of 
1-25 µg/mL.  These cell-based functional activity assays demonstrated the 
immunomodulatory activity induced by PF-06755347.
In healthy human whole blood samples, PF-06755347 modulated a panel of pro- and 
anti-inflammatory cytokines and chemokines, and was shown to bind Complement 
component 1q (C1q), preventing the initiation of complement -dependent cytotoxicity 
(CDC).  Additional studies demonstrated that PF-06755347 induces self-limited complement 
activation that is governed by Factors H and I and results in the generation of proteolytically 
inactive product of complement component 3b (iC3b) which is associated with the induction 
of tolerance.10 Together these in vitro data demonstrated that PF-06755347 binds to multiple 
FcRs expressed on different immune cell subtypes and to C1q and affects several activities 
associated with an immuno-modulatory role that is also seen with IVIg but at higher 
concentrations.
The anti-autoimmune activity of PF-06755347 was evaluated in the rat EAN model, a well 
characterized model of CIDP induced by administration of bovine myelin.  PF-06755347 
ameliorated the neurological disease score in rats with EAN.  Although an ED50 was not 
calculated in this model, efficacy was achieved at 25-fold lower doses than for IVIg 


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(40 mg/kg vs 1000 mg/kg respectively).  Additional measures included body weight and 
Rotarod scores (measures balance and endurance), which correlated with the improvement in 
the neurological disease scores seen with PF-06755347.4  
The mouse collagen -induced arthritis (CIA) model is a well characterized model of 
rheumatoid arthritis and is used as a model of immune complex -mediated autoimmune 
disorders.  PF-06755347 ameliorated the CIA disease score, body weight loss and 
histopathology endpoints at doses 25-40 fold lower than the dose of IVIg administered.  The 
data from the mouse CIA model, in which PF-06755347 demonstrated an amelioration of the 
disease with a dose-responsive trend, was incorporated into the projections of the human 
therapeutic systemic drug concentration modeling.
2.2.2. Nonclinical Pharmacokinetics and Metabolism 
After single-dose IV administration of PF-06755347 to mice (pharmacology species), rats, 
and monkeys (toxicology species), the PK of PF-06755347 were characterized by low 
systemic clearance (CL) and low to moderate apparent volumes of distribution at steady-state 
(Vss).  Mean terminal elimination half-life (t½) values for PF-06755347 were 313 hours 
(approximately 13 days) in mice, 42 to 91 hours in rats, and 34 to 84 hours in monkeys. 
After weekly IV administration of PF-06755347 for up to 6-weeks in rats and monkeys, there 
were no apparent sex-related differences in systemic exposure (as assessed by maximum 
observed plasma concentration [Cmax] and area under the concentration-time curve from time 
0 to 168 hours [AUC168]).  Mean systemic exposure increased with increasing dose in an 
approximately dose-proportional or slightly higher than dose-proportional manner.  The 
overall incidence of ADA induction to PF-06755347 was 11% (22/199 animals) in rats and 
62% (24/39 animals) in monkeys for all PF-06755347 dosed animals assessed.  In monkeys, 
PF-06755347 serum exposures were generally similar in ADA-positive animals compared to 
ADA-negative animals. 
No in vitro or in vivo PK drug interaction studies have been performed to date.  
PF-06755347 is expected to have immuno-modulatory activity, affecting various cytokines.  
Cytokines have been shown to modulate expression of CYP enzymes and transporters.5,6  
Therefore, treatment with PF-06755347 could theoretically affect CYP enzyme and 
transporter levels through normalization of inflammatory states, and consequently modulate 
the clearance of concomitant medications that are substrates for these enzymes or 
transporters.  However, cytokine mediated- drug interactions observed with clinically 
immuno-modulatory drugs have been modest in magnitude, resulting in less than a 2x change 
in the exposure of coadministered- small molecule drugs.7
The primary clearance mechanism of PF-06755347 is via nonspecific catabolic degradation 
with some evidence of target-mediated disposition in monkeys.  At expected therapeutic 
doses, target-mediated disposition is predicted to be modest and therefore, it is unlikely that 
concomitant medication will significantly alter the clearance of PF-06755347, even if target 
expression is affected.


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2.2.3. Nonclinical Safety
The nonclinical safety profile of PF-06755347 has been evaluated using in vitro assays to 
measure cytokine and complement cascade modulation, cardiovascular (CV) safety 
pharmacology studies and toxicology studies of up to 6 weeks in duration in rats and 
cynomolgus monkeys.  In vivo studies primarily used a complex, stepped IV infusion 
paradigm.
In vitro, PF-06755347 increased the release of pro-inflammatory cytokines IL-6, IFN, and 
TNFin human whole blood, and complement component C4a in human and cynomolgus 
monkey serum, in a concentration-dependent manner.  The EC20 values were calculated for 
these experiments and presented in Table 5.
Table 5.
In Vitro PF-06755347 Potency for Increases in Cytokines and 
Complement Component 
Analyte (Species)
EC20 (µg/mL)
95% Reference Interval
IL6 (Human)
1.95
0.78 – 4.89
IFN(Human)
5.30
1.24 – 22.67
TNF(Human)
6.33
1.87 – 21.47
C4a (Human)
9.89
3.57 – 27.42
C4a (Cynomolgus monkey)
4.35
2.38 – 7.94
Cardiovascular safety pharmacology studies were conducted in rats and cynomolgus 
monkeys that were surgically implanted with telemetry devices.  These studies were 
conducted across a range of IV infusion rates and concentrations.  In rats, doses from 1 to 
160 mg/kg were infused over a range of durations from 1 to 5.5 hours.  Small increases in 
heart rate, BP and body temperature were observed that did not demonstrate dose 
dependence.
In cynomolgus monkeys, multiple safety pharmacology studies were conducted.  Variable 
infusion rates and durations allowed a wide dose range (0.1 to 990 mg/kg) and different 
infusion regimens to be assessed.  The first pivotal study evaluated doses of 25, 224, and 
750 mg/kg and the second assessed doses of 0.1, 10, and 50 mg/kg.  Hemodynamic changes 
including both increases and decreases in BP and heart rate were noted.  Antihistamine 
premedication was utilized in the initial high dose range studies in cynomolgus monkeys but
was not used in the subsequent studies to ensure the pharmacology of PF-06755347 could be 
fully evaluated.  In the 2 pivotal cardiovascular studies, cynomolgus monkeys demonstrated a 
low incidence of emesis and retching at doses ≥10 mg/kg, as well as minimally increased 
heart rate and decreased BP that showed no dose dependency.  At 50 mg/kg, the high dose in 
the second pivotal study, emesis was observed in 1/4 cynomolgus monkeys with minimal 
cardiovascular changes and no change in body temperature.  At 50 mg/kg in the safety 
pharmacology study, the Cmax was 966 µg/mL, which is 5680x the predicted human Cmax of 
0.17 µg/mL at the anticipated human starting dose of 0.01 mg/kg.


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Multiple rat and cynomolgus monkey repeat-dose toxicity studies were conducted.  The first 
set of toxicity studies used relatively high dose ranges while the second set of studies 
employed a lower dose range as described.
In the initial non-pivotal rat toxicity study, PF-06755347 was tolerated at doses of 160, 508, 
and 1611 mg/kg/week although it produced changes in a number of parameters.  However, 
these effects were considered to be non-adverse due to low incidence and/or magnitude of the 
effects.  Based on these results, the doses selected for the initial high dose range pivotal study 
in rats were 160, 566, and 2000 mg/kg/week.
In the initial pivotal higher dose range study in rats, a single dose of 2000 mg/kg/week was 
not tolerated.  Therefore, the high dose of 2000 mg/kg was lowered to 1200 mg/kg/week for 
the second weekly dose and the remainder of the study.  A total of 10 animals were 
euthanized in a moribund condition due to hind limb dysfunction associated with 
extravasation of the test article (6 rats at 2000 mg/kg, 3 rats at 566 mg/kg/week, and 1 rat at 
160 mg/kg/week).  These euthanized animals demonstrated clinical signs (swollen and 
limited use of the hind limb, swollen inguinal region), macroscopic findings (enlarged tarsus 
or swollen foot pad joint, thickened tissue or mass at the catheter/infusion sites), and 
microscopic findings (chronic-active inflammation of hind limb or at the catheter/infusion 
sites) that were associated with extravasation of the test article.  After 7 weekly doses, there 
were no adverse findings in surviving animals.
These hind limb findings were not reproduced in the second pivotal rat study.  In this lower 
dose range toxicity study, doses of 1, 10, or 160 mg/kg/week were administered over 6 weeks 
(7 weekly doses).  There were no PF-06755347-related effects on mortality, clinical signs, 
body weights, food consumption, ophthalmology, hematology, coagulation, clinical 
chemistry, or urinalysis parameters, immunophenotyping parameters (other than spleen 
activated dendritic cells), changes in concentrations of total cell count (TCC), or organ 
weight, macroscopic or microscopic changes.  PF-06755347 did produce non-adverse 
changes in cytokines (IL-6, IL-10, IL-13, IL-17, and TNF-) at ≥1 mg/kg and IL-4 at 
≥10 mg/kg. The no observed adverse effect level (NOAEL) was considered to be 
160 mg/kg/week (selected on the basis that this dose had no increased mortality relative to 
controls), with a Day 36 mean Cmax of 2210 µg/mL and mean AUC168 of 64000 µg·hr/mL.
In the non-pivotal toxicity study in cynomolgus monkeys, test article -related increases in 
cytokines IL-6, IL-10, and IL-1RA as well as complement activation products were observed 
at ≥150 mg/kg/week and were reversible.  In the initial higher dose range pivotal cynomolgus 
monkey study, doses of 50, 224, and 1000 mg/kg/week were administered over 6 weeks 
(7 weekly doses).  No adverse test article-related effects were noted at <224 mg/kg although 
PF-06755347 induced changes in immune cell subtypes, cytokines, and complement 
activation products.  In the second, lower dose range pivotal toxicity study, doses of 0.1, 10, 
or 50 mg/kg/week were administered over 6 weeks (7 weekly doses).  In this study, there 
were no PF-06755347-related effects on mortality, clinical observations, ophthalmic 
observations, body weight parameters, electrocardiography parameters, organ weight 
parameters, urinalysis, coagulation test parameters, macroscopic observations, and 
microscopic findings.  In addition, no test article -related changes were observed in the 


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numbers of peripheral blood leukocyte subsets of T cells, helper T cells, cytotoxic T cells, 
B cells, myeloid dendritic cells (mDC), or CD14+ monocytes, or in the percentage of CD14+ 
monocytes, mDC, or B cells expressing markers of activation, or in CD14 expression (MFI) 
on monocytes.  Test article -related, non-adverse decreases in peripheral blood 
CD3-CD159a+ natural killer (NK) cells (0.14x-0.41x baseline) and regulatory T cells 
(0.45x-0.62x baseline) were observed for males and females administered 50 mg/kg/week of 
PF-06755347.  The decreases of CD3-CD16+ NK cells observed for all animals administered 
10 or 50 mg/kg/week are likely due to the inability of the flow cytometry antibody to bind 
CD16 in the presence of the test article. Non-adverse test article related findings for 
cytokines and complement activation products included increases in IL-10, sC5b-9, and Bb 
concentrations at ≥0.1 mg/kg and increases in IL-1RA, IL-6, C3a, and C4a concentrations at 
≥10 mg/kg.  The NOAEL in this study is the highest dose of 50 mg/kg which corresponded 
to mean Cmax and AUC168 values of 1130 µg/mL and 34000 µg·hr/mL, respectively, on 
Day 36 of the dosing phase.
Mortality occurred in the rat toxicity studies.  The causes of mortality/morbidity for animals 
found dead or euthanized for humane reasons were attributed to procedural issues arising 
from long term infusion and were not considered to be due to PF-06755347.  These included 
blocked catheters, retracted catheters, complications from blood collection, extravasation of 
test article, infection, trauma of undetermined origin, air in infusion line, and complications 
during re-catheterization surgery.
In the second, lower dose range pivotal rat toxicity study, 6 of the 9 deaths occurred during 
or as a result of repair surgery and are not considered to be due to test article.  One animal 
was euthanized on Day 39 in a moribund condition resulting from infection at catheter site 
resulting in sepsis. The 2 undetermined deaths, 1 control and one 1 mg/kg/week, are 
considered to be incidental and not due to the test article as there was no deaths at 10 and 
160 mg/kg/week.
The variability of cytokine and complement activation product concentrations in untreated 
rats and monkeys is not available in the published literature.  Therefore, these data were 
compiled from vehicle control and pre-dose baseline samples across a number of the 
nonclinical studies.  These control cytokine and complement activation products data allowed 
comparison between cytokine and complement activation product concentrations at lowest 
observed effect level (LOEL) doses and untreated control samples.  Many, but not all, of the 
concentrations for these parameters at the LOEL doses were within the control range thereby 
proving additional support for the conclusion that these increases were not adverse.  In 
addition, although PF-06755347 increased cytokines and complement activation factors 
across a wide range of doses in both rat and cynomolgus monkeys the dose response curve 
was relatively flat.  No meaningful increase in cytokine levels were observed beyond 
10 mg/kg/week. For the 2 cynomolgus monkey studies, the overall NOAEL is considered to 
be 224 mg/kg/week.  This conclusion is based on the euthanasia of 2 animals in the 
1000 mg/kg/week dose group and 1 animal in the control group that was attributed to 
infection and not to test article.  However, in order to eliminate the uncertainty related to the 
possible test article -related causation of these deaths, the next lower dose of 
224 mg/kg/week is determined to be the overall cynomolgus monkey NOAEL.  Thus, 


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systemic exposure (Cmax and AUC168) at the NOAEL dose of 224 mg/kg/week in 
cynomolgus monkeys was 5870 µg/mL and 215000 µg·hr/mL, respectively.
In considering the 5 pivotal 6-week toxicology studies as a whole, the overall lowest NOAEL 
is concluded to be the 160 mg/kg/week dose in the second, lower dose rat study.  This dose 
had no increased mortality relative to controls.  The systemic exposure (Cmax and AUC168) at 
this overall NOAEL in rats was 2210 µg/mL and 64000 µg·hr/mL, respectively.
The proposed starting clinical dose of 0.01 mg/kg is expected to yield a Cmax of 0.17 µg/mL.  
This value is similar to the human in vitro cytokine release assay EC3 for IL-6 for the most 
sensitive endpoint for cytokine release or complement activation product and also 
corresponds to a projected 1% B cell receptor occupancy. This estimated Cmax of 
0.17 µg/mL at the proposed starting clinical dose of 0.01 mg/kg is 13000x and 6647x lower 
than the Cmax exposures at the NOAELs in rats (160 mg/kg/week) and cynomolgus monkeys 
(50 mg/kg/week), respectively.  The PK stopping limits proposed in the first in human (FIH)
study were chosen based on the exposures of PF-06755347 achieved at the NOAEL dose of 
50 mg/kg/week on Day 36 (1130 µg/mL) from the 6-week lower dose range cynomolgus 
monkey toxicity study.
The exposure margins at the starting dose are robust and, therefore considered sufficiently 
broad to compensate for the greater human in vitro sensitivity to cytokine release when 
compared to monkey.
In summary, the nonclinical program with PF-06755347 identified the expected 
pharmacological effects including modulation of cytokine release, detection of complement 
activation products and changes in immune cell subtypes.  These changes were generally 
transient over the 24 hrs post-start of infusion interval and not associated with microscopic 
changes at the NOAEL doses of 160 mg/kg/week (rats) and 224 mg/kg/week (cynomolgus 
monkeys) although there were monitorable and reversible effects on BP, heart rate, and body 
temperature.  The nonclinical program supports clinical trials with PF-06755347 up to 
6 weeks in duration.
2.3. Benefit/Risk Assessment
PF-06755347 is not expected to provide any clinical benefit to healthy participants but it may 
provide a transient increase in platelet count in participants with persistent or chronic ITP.  
This study is designed primarily to generate safety, tolerability, and pharmacokinetic data 
that will support further clinical development.
PF-06755347 has been shown to cause transient elevation in pro-inflammatory cytokines. 
Symptoms associated with CRS vary greatly and may be difficult to distinguish from other 
conditions.  The more common symptoms include fever, nausea, headache, tachycardia, 
hypotension, rash and shortness of breath.  The severity of symptoms can be mild to life 
threatening and thus there should be a high suspicion for CRS if these symptoms occur.  
Cytokines will be analyzed to determine if cytokine elevation consistent with CRS is 
observed (see Section 10.10).  The severity of CRS will be assessed according to the most


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recent consensus grading from the American Society for Transplantation and Cellular 
Therapy (ASTCT).2
For study participants with ITP, there is an increased risk of procedure-related 
bleeding/bruising from subcutaneous injections, mitigated by the lower bound of platelets in 
the eligibility criteria. An increased risk of thrombosis has also been reported in ITP.15 High 
dose single IV administration of PF-06755347 may transiently lower platelet counts in 
healthy participants, while repeat IV administration in non-clinical studies may also lower 
platelet counts.  The predicted Cmax with SC administration in ITP participants is
approximately 6 fold lower than observed Cmax at 1 mg/kg at which the reduction in platelet 
count was observed in healthy participant (see Table 6). More detailed information about the 
known and expected benefits and risks and reasonably expected adverse events of 
PF-06755347 may be found in the investigators brochure, which is the SRSD for this study. 
Each study site should have a COVID-19 risk mitigation policy (RMP), which documents the 
site’s COVID-19 virus testing strategy for participants and staff, social distancing measures, 
and management of COVID-19-like symptoms.
To account for the widespread deployment of COVID-19 vaccine during the COVID-19 
pandemic, the benefit/risk analysis has assessed both the impact of PF-06755347 on risk of 
COVID-19 disease in study participants who may become infected with SARS-CoV-2 and 
the efficacy of COVID-19 vaccines.
The benefit/risk analysis for study participants for COVID-19 related illness during the 
COVID-19 pandemic is similar to the benefit/risk prior to COVID-19. PF-06755347 is 
proposed to be an immunomodulator similar to IVIg, and so its safety in humans can 
reasonably be predicted from clinical experience with IVIg. PF-06755347 is not an 
immunosuppressant that might render an individual more susceptible to the impact of 
COVID-19. IVIg has been used in COVID-19 infected individuals because of its known 
immunomodulatory effects and is reported in uncontrolled trials to be helpful in critically ill 
individuals. There are currently no reports of injury because of the immunomodulatory 
effects of IVIg in COVID-19 infected individuals. 
In contrast, the benefit/risk analysis for study participants who are scheduled to receive or 
have received a COVID-19 vaccine suggests that appropriate interval between vaccination 
and administration of PF-06755347 is prudent because of the potential for an
immunomodulatory effect to interfere with development of the intended immune response to 
the vaccine.  While this has not be been studied for PF-06755347, extrapolation from other 
immunodulatory/immunosuppressive agents suggests at least a 28 day interval after 
completion of the vaccination course should be sufficient to allow a desired immune 
response.
By the time of discharge after study confinement on Day 8, approximately 3 terminal 
half-lives of the study drug will have elapsed.  Coupled with the rapidity of the cytokine 
response to study drug, longer duration of confinement for additional observation appears 
unnecessary. The on-site follow up requirements for the study are standard timelines for 
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3. OBJECTIVES AND ENDPOINTS
Primary Objective: 
Primary Endpoints: 

To evaluate safety and tolerability 
following a single dose of PF-06755347 
in the study population. 

Assessment of AEs, clinical laboratory tests, vital signs, 
body temperature, cardiac monitoring and cardiac 
telemetry (where collected) and 12-lead ECG.
Secondary Objective: 
Secondary Endpoints: 

To characterize the plasma PK profile 
following a single of PF-06755347 in 
the study population. 

PK parameters derived from plasma PF-06755347 
concentration:a
Cmax, Tmax, AUClast, AUCinf, t½, if data permit.

To evaluate the immunogenicity profile 
following a single dose of PF-06755347 
in the study population. 

Incidence of the development of anti-drug antibody to 
PF-06755347.

 
 
 
 
Tertiary Objective: 
Tertiary Endpoints: 

To further characterize the plasma PK 
profile following a single dose of 
PF-06755347 in the study population. 

PK parameters derived from plasma PF-06755347 
concentration:a
Cmax (dn), AUClast (dn), AUCinf (dn), CL, Vss, CL/F, and 
Vz/F, if applicable.

 
 

Collection of biospecimens unless prohibited by local 
regulations or ethics committee decision.  Additional 
information on collection and potential use is provided in 
the Biospecimens section.
a.
For a complete definition of all PK parameters, refer to Section 9.5.1.
4. STUDY DESIGN
4.1. Overall Design 
This is a Phase 1, randomized, double-blind, Sponsor-open, placebo -controlled,
first-in-human single -ascending dose study to evaluate the safety, tolerability, and PK of 
PF-06755347 in healthy adult male participants by IV and SC administration and in male or 
female participants with persistent or chronic ITP by SC administration. Personnel, trained 
in advanced cardiac life support, emergency resuscitative equipment and the management of 
anaphylaxis, are immediately available to treat systemic reactions under the supervision of a 
physician.  IV fluids, epinephrine, antihistamine and methylprednisolone will be available for 
immediate parenteral use in the event of an anaphylactic reaction.  
A schematic of the overall study design is provided in Section 1.2 (note actual dose levels to 
be administered beyond the starting dose are subject to change, see Section 4.2.1.3). A total
of approximately 75 healthy adult male participants are planned to be randomized to either 
receive PF-06755347 or placebo by intravenous or subcutaneous administration in a 
3:1 allocation ratio.  All participants with ITP will receive PF-06755347. Clinical data from 
the IV cohorts supporting the transition to SC dosing are summarized in the IB, Section 6.  
SC Cohorts 7-14 are planned, Cohort 7 will have 4 male participants (3 active and 1 placebo)
CCI
CCI


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and Cohorts 9-11 will have 8 male participants (6 active and 2 placebo). Cohort 12 (optional 
Japanese cohort) will include approximately 4-8 male Japanese healthy participants and 
Cohorts 13 and 14 combined will include a maximum of 12 male or female participants with 
ITP.  The total number of participants randomized will not exceed 87.  The ITP cohort dosing 
will start after completion of the 50 mg dose cohort in HPs.  
Participants within each cohort will be dosed using a sequential dosing scheme. For all
cohorts, only a single participant will be dosed at any given time. Based on the emerging 
safety data to date with IV dosing, cytokine and laboratory abnormalities reach their peak 
levels within the first few hours following PF-06755347 Cmax and are resolved within
24 hours. The Cmax was predicted to be 24 -48 hours with SC administration, however 
preliminary data from Cohort 7 supports increasing the monitoring period to 96-hr for safety.
A safety review of the post-dose 72-hour data (96-hour for SC administration) will occur for 
every participant in order to proceed with dosing the next participant. A minimum of 
96-hours (120-hours for SC administration) between dosing of consecutive participants. A 
safety review evaluation meeting may be required in order to proceed with dosing the next 
participant. The safety review period can be extended if deemed necessary at the discretion 
of any PI (in consultation with the Sponsor medical monitor).  Dose levels selected for 
optional cohorts will be selected based on the assumption that resulting clinical exposures 
will not exceed protocol defined PK stopping limits.
Only males will be enrolled in the healthy participant cohorts in an attempt to reduce overall
variability because there are significant gender variations in immune responses.16 Healthy 
Participants will  be screened to ensure that they do not have any autoimmune disease or 
immune deficiency prior to enrollment. Participants with ITP that have active autoimmune 
disease in the opinion of the investigator will be excluded. Participants with a history of 
migraine will also be excluded so as not to confound pro-inflammatory adverse event
assessments using the Common Terminology Criteria for Adverse Events (CTCAE) criteria.  
The age range will be 18-55 years in order to ensure adequate renal function and reduce the 
risk of thrombo-embolic events. Screening evaluation will occur within 56 days prior to 
dosing.
Male and female participants will be enrolled in the ITP cohorts. In adults, ITP is more 
common in females than in males. Therefore, it is important to allow for assessment of 
safety, tolerability and PK in both males and females. 
PF-06755347 has been administered to male and female cynomolgus monkeys by IV 
infusion and SC bolus injection across a wide range of doses in multiple studies. 
PF-06755347 PK parameters (Cmax, Tmax, AUC168) were similar between male and female 
cynomolgus monkeys at all doses. Additionally, incidence and magnitude of IL-6 or IL-1RA 
release was similar between the sexes. Therefore, nonclinical data support the expectation 
that no dose adjustment is needed in female participants in B7801001. 


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Eligible participants who meet the entry criteria will be admitted on Day -1 and are required 
to stay overnight through completion of Day 8 evaluations.  At the discretion of the study site 
participants may be admitted on Day -2. Participants will return for outpatient visits per the 
Schedule of Activities (SoA) through approximately Day 36 (≤1 mg/kg IV dose level) or 
Day 71 (>1 mg/kg IV dose level and all subcutaneous dose levels for a total of approximately 
5 or 10 weeks study participation, respectively from first dose to final follow-up, excluding 
screening.  The follow-up period may be extended for a participant and/or a cohort if any 
participant in the cohort tests positive for anti-drug antibody to PF-06755347 at the 
scheduled follow-up visit, or has detectable concentration of PF-06755347 at final follow-up 
visit.
If a participant discontinues during the study, the participant may be replaced at the 
discretion of the Sponsor in consultation with the PI.  Doses in the dose escalation sequence 
may be repeated or adjusted depending on the results obtained during the study to explore 
different doses and/or infusion/dosing rates as needed.  The total number of participants 
including the subcutaneous and optional cohorts will not exceed 87.
Some of the cohorts in the study may not be conducted if study objectives are deemed 
accomplished or if directed by emergent data. Participants in any cohort may be confined for 
a period beyond what is required in the SoA at the discretion of the investigator for safety 
reasons and/or to accommodate the frequency of required outpatient visits.
 
 
4.2. Dose Justification
4.2.1. Human Predictions
4.2.1.1. Prediction of Human Pharmacokinetics 
The PK data from cynomolgus monkeys were characterized using a 2-compartmental model 
incorporating linear and non-linear clearance (Vmax/Km model), to describe the observed 
non-linear PK.  Subsequently, a human PK model was established by allometrically scaling 
the PK parameters from monkey to human.  The scaling was performed to be the most 
conservative (produce the highest exposure) by using scaling factor of 0.75 for Vmax and 1 for 
Km.  In humans the projected serum CL and Vss for the linear process were 0.11 mL/hr/kg 
and 87 mL/kg respectively, and the parameters for non-linear clearance mechanism (Vmax and 
Km) were predicted to be 385 µg/kg/hr and 942 nM, respectively. The terminal half-life was 
estimated to be approximately 8-9 days.
CCI


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4.2.1.2. Prediction of Human Efficacious Exposure
The data obtained from the pharmacology study in a CIA mouse model were fitted using a 
direct effect Imax model where either average concentration (Cav) or trough concentration 
(Cmin) were assumed to drive the response (% normalized disease score).  The human 
efficacious concentration (Ceff) was defined as the Cav or Cmin to achieve the expected IC90s 
in human, which was calculated based on the mouse IC90s after correcting for the 
mouse-human potency difference.  The potency correction was based on the in vitro FcRIIB 
and FcRIIIA binding assays, which suggests a more than 10x higher binding avidity for 
human FcRIIB and FcRIIIA compared to mouse.  The projected Ceff is 37 µg/mL for 
Cav (or 6 µg/mL for Cmin).
4.2.1.3. Clinical Dose Selection
4.2.1.3.1. Intravenous Administration in Healthy Participants
The starting dose of PF-06755347 proposed for this study was 0.01 mg/kg (IV).  Subsequent 
dose escalation was to proceed to either the highest dose deemed to be well tolerated with an 
acceptable safety profile or the achievement of plasma exposure equivalent to the PK 
stopping limits. The PK stopping limits proposed in this study were chosen based on the 
Day 36 exposures of PF-06755347 achieved at the NOAEL (50 mg/kg weekly) from the 
6-week lower dose range monkey toxicity study (see Section 2.2.3). Human PK parameters 
and efficacious exposure predicted for PF-06755347, along with the toxicokinetic data, and 
anticipated binding and pharmacological activity, were used to establish the dose range to be 
studied.  The dose range in this study aimed to bracket the expected clinically efficacious 
exposure range in humans, while allowing for uncertainty in the prediction of targeted 
efficacious concentration and PK.  
Table 6.
Observed Human Exposure and Safety Margin Following Single IV 
Administration of PF-06755347
Dose (mg/kg)
Human Exposure of Plasma PF-06755347a
Observed Safety Marginb
Cmax (µg/mL)
AUC168 (µg·hr/mL)
Cmax
AUC168
0.01
0.112
1.41
10089
24113
0.03
0.446
10.5
2534
3238
0.1
1.65
45.2
685
752
0.3 
4.70
139.0
240
245
0.7 
12.4
281.0
91
121
1 
24.7
490.0
46
69
a. Cmax and AUC168 are observed exposure levels following IV administration. Please refer to Investigator's 
Brochure for additional details.
b. Safety margins for Cmax and AUC are calculated using the exposure limiting criteria (NOAEL in lower dose 
range monkey toxicity study: Cmax = 1130 µg/mL and AUC168 = 34000 µg·hr/mL); and equal to the ratio of 
limiting criteria/observed Cmax or AUC168.
The starting IV dose of 0.01 mg/kg was projected to be safe with anticipated level of 
Fc-gamma receptor occupancy estimated at 1% and minimal associated pharmacological
activity.  Non-clinical human pharmacology and non-human primate (NHP) toxicology 
studies suggested that this dose would achieve greater than 5000-fold safety margin over the 
NOAEL, and would not be associated with any clinical symptoms or vital sign changes. The
dose was predicted to be associated with low level transient systemic IL-6 release, but was


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not expected to be associated with elevated levels of other cytokines or with any evidence of 
complement activation.  
The observed Cmax (0.112 µg/mL; Table 6) at the starting IV dose was approximately 10-fold 
lower than the Cmax achieved at the lowest dose level tested in the 6-week pivotal toxicity 
study in cynomolgus monkeys (0.1 mg/kg, 1.77 µg/mL), and was similar to the Cmax on 
Day 1 of the investigative monkey study (8384439/18GR088) at the 2 lowest doses tested of 
0.005 (0.097 µg/mL) and 0.01 mg/kg (0.168 µg/mL).  All doses, 0.005, 0.01 and 0.05 mg/kg, 
produced minimal transient elevations in IL-6 but not in TNFor INFor complement.  
This IL-6-only response at ≤0.05 mg/kg was less than that observed at 0.1 mg/kg in 
monkeys, where non-adverse, minimal changes in cytokine and complement activation 
products were observed.  There were no effects on immune cells, or changes in clinical signs, 
other laboratory parameters or macroscopic and microscopic observations at 0.1 mg/kg in 
monkeys.  Minimal changes in heart rate were observed at 0.1 mg/kg in NHP, with no other 
hemodynamic changes (more details can be found in the accompanying IB).  Thus the safety 
data package supports the choice of the proposed starting dose of 0.01 mg/kg.
A receptor occupancy calculation was also performed.  Since PF-06755347 binds to multiple 
FcRs on multiple cells, the apparent Kd was determined using in vitro human whole blood.  
PF-06755347 exhibited the greatest binding avidity towards B cells, with an apparent Kd of 
13.95 µg/mL.  Using this most conservative apparent Kd value, the predicted peak receptor 
occupancy achieved at the starting dose of 0.01 mg/kg was expected to be approximately 1%,
which also represents an EC3 for in vitro IL-6 release in human whole blood, the most 
sensitive functional assay.  
Furthermore, the 0.01 mg/kg starting dose is 1/200,000th of the prescribed loading dose of 
2 g/kg for IVIg (based on Gamunex®-C US prescribing information [USPI]9 for CIDP) on a 
mg/kg basis (or 1/200th to 1/2000th of an estimated loading dose of IVIg, if corrected for the 
approximately 100-1000x higher human FcR binding avidity for PF-06755347 vs. IVIg). 
Dose escalation beyond the starting dose will be dictated by the criteria summarized in 
Section 6.7 and will aim to occur in incremental increases of no more than half-log 
(ie, 3.3 fold) based on predicted exposure, with smaller increments if required due to 
emerging safety data or once the expected PF-06755347 exposure approaches the PK 
stopping limit. The actual doses to be evaluated in the escalation sequence as well as the 
number of dose levels to be evaluated may be adjusted according to emerging safety, 
tolerability and PK data, provided the dose escalation criteria specified in Section 6.6 and 
Section 6.7 are not violated.  These criteria are applicable to both IV and SC administration. 
A body weight-based dosing approach (mg/kg) was used in this study for the IV cohorts with 
the goal of reducing inter-individual variations in IV infusion/dosing rate and PK exposure.  
PF-06755347 was administered as a single infusion over 60 minutes for the starting dose of 
0.01 mg/kg.  Based on emerging safety data of cytokine elevation at the 1 mg/kg dose level, 
the infusion duration was increased to 3 hours for an expansion cohort at 1 mg/kg. 
(Section 6.1.1.1). The increase in infusion duration was expected to modulate the tolerability 
of PF-06755347. Safety data from the 1 mg/kg expansion cohort showed that an increase in 


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infusion duration to 3 hours did not modulate the tolerability profile of PF-06755347 and 
subsequently, the next cohort used 0.7 mg/kg infused over 1 hour. Guidelines for the 
proposed infusion rate at each dose level are provided in Section 6.1.1.1.  However, the 
actual dosing rate could have been reduced and/or the overall infusion time increased at the 
discretion of the PI and upon the review of the available safety data.  The overall infusion 
time was not to exceed 4 hrs. If deemed appropriate by the PI, concomitant medications 
(such as acetaminophen and diphenhydramine) coupled with adjustment of dosing rate could 
have been implemented to manage possible emerging symptoms that may have been related 
to transient pro-inflammatory activity.
4.2.1.3.2. Subcutaneous Administration in Healthy Participants
Following IV administration of PF-06755347, the observed safety data to date has shown 
Grades 1 and 2 CRS associated with IV doses of 1.0 and 0.7 mg/kg, respectively.  Cytokine 
(eg, IL-6) elevation peaked within the first few hours following IV administration and 
returned to baseline levels within 24 hours. These results may suggest that the degree of 
cytokine release is dose dependent and potentially correlated with PF-06755347 Cmax and the 
rate of rise to achieve Cmax. SC dosing of PF-06755347 offers the potential to blunt the 
severity of CRS by reducing the Cmax and delaying the time to achieve Cmax (Tmax). The 
observed Cmax (0.895 µg/mL) at the proposed starting SC dose of 25 mg is approximately 
5-fold lower than the observed mean Cmax (4.7 µg/mL) achieved at the highest tolerated IV
dose level of 0.3 mg/kg (Table 6), with a safety margin of 1263 for Cmax and 345 for AUC168. 
Observed Cmax values in subsequent dose levels of 50 and 100 mg were of 1.37 and 
2.64 µg/mL respectively; approximately 3.5-fold and 1.8-fold lower than the values observed 
at the 0.3 mg/kg IV dose level.  The SC dose level of 300 mg will only be explored when SC 
doses up to 200 mg levels are deemed to be safe and well tolerated and within the PK 
stopping limit criteria. 
In order to support subcutaneous delivery of PF-06755347, a toxicology study (Study 
14MA141, IB Section 5.3.7) in NHP was conducted with a single 250 mg/kg SC dose and 
the results showed that the drug was tolerated. 
The dose for the optional Japanese SC Cohort 12, if conducted, will be the highest dose from 
Cohorts 7-11 that is found to be safe and well tolerated.


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Table 7.
Observed/Predicted Human Exposures and Safety Margins Following 
Single SC Administration of PF 06755347
Dose (mg)a
Human Exposure of Plasma PF-06755347
Safety Marginb
Cmax (µg/mL)
AUC576 or AUC168 (SC) 
(µg·hr/mL)
Cmax
AUC
25 mg SCc
0.895
98.5
1263
345
50 mg SCc
1.37
159
825
214
100 mg SCc
2.64
315
428
108
200 mg SC
5.28
630
214
54
300 mg SC
7.92
945
143
36
a.
Depending on the safety and PK data available, dose escalation may be adjusted to doses other than those 
outlined above while following dose progression and stopping rules outlined in Section 6.6 and 
Section 6.7.
b.
Safety margins for Cmax and AUC are calculated using the exposure limiting criteria (NOAEL in lower 
dose range monkey toxicity study: Cmax = 1130 µg/mL and AUC168 = 34000 µg·hr/mL); and equal to the 
ratio of limiting criteria/projected Cmax or AUC168 or AUC576 (SC).
c.
Observed exposures and safety margins are reported for 25 mg, 50 mg and 100 mg SC dose.
4.2.1.3.3. Subcutaneous Administration in Participants with ITP
The starting dose of the ITP cohorts will be dependent on the equivalent dose levels in 
healthy participants having been studied and been deemed to be safe and well tolerated.  
The dose levels to be tested in participants with ITP may include SC doses of 25 mg, 50 mg
or 100 mg.  The observed mean Cav after administration of a single 25 mg SC dose in HP was 
0.586 ug/ml. This Cav is approximately 2-fold higher than the Cav of 0.25 ug/ml for 
≥90% receptor occupancy for human FcγR. Thus it is expected that the lowest proposed 
dose in participants with ITP in this study could have pharmacological activity after a single 
dose. 
The starting dose for participants with ITP will be 25 mg based upon the safety and 
tolerability data in HP. 
Dosing progression and escalation are outlined in Section 6.6 and 6.7.
4.3. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study. 
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria for Healthy Participants
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
Healthy male participants who, at the time of screening, are between the ages of 
18 and 55 years, inclusive.  Healthy is defined as no clinically relevant abnormalities 
identified by a detailed medical history, full physical examination, including 
temperature, BP and pulse rate measurement, pulse oximetry, 12-lead ECG or clinical 
laboratory tests. 
Type of Participant and Disease Characteristics:
Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, and other study procedures.
Chest X-ray with no evidence of current, active TB or previous inactive TB, general 
infections, heart failure, malignancy, or other clinically significant abnormalities 
taken at Screening or within 3 months prior to Screening and read by a qualified 
radiologist.
Additional criterion for participants to be enrolled in Japanese cohort only: Japanese 
participants who have four Japanese biologic grandparents born in Japan.
Weight:
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50 kg such 
that the calculated total volume of the IV infusion of PF-06755347 will not exceed 
1 liter.
Informed Consent
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 for Healthy Participants
Participants with any of the following characteristics/conditions will not be included in the 
study:
Medical Conditions
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or 


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allergic disease (but excluding untreated, asymptomatic, seasonal allergies at the time 
of dosing).
Diagnostic assessments
2. A positive urine drug screen.
3. Participants with a history of autoimmune disorders and other conditions that 
compromise or impair the immune system (including but not limited to: Crohn’s 
Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, 
Graves’ disease, and asthma) or have a current positive result for the following; 
rheumatoid factor, anti-nuclear antibody, or abnormal free triiodothyronine (T3), 
free thyroxine (T4), thyroid stimulating hormone (TSH), or thyroid stimulating 
antibody (TSAb) suggestive of thyroid disease. 
4. Participants with a history of autoimmune deficiency or current evidence of total 
immunoglobulin G (IgG) or total immunoglobulin A (IgA) deficiency. 
5. Participants with a history of migraine. 
6. Participants with a history or current evidence from lab safety tests of clinically 
significant dyslipidemia in the opinion of the investigator. 
7. Participants with a history of allergic or anaphylactic reaction to any drug including 
immunoglobulin.
8. Participants with a fever or skin rash within 7 days prior to dosing.
9. History of active infections within 28 days prior to the screening visit.
10. Participants with a history of or current positive results for any of the following 
serological tests: Hepatitis B surface antigen (HepBsAg), Hepatitis B core antibody 
(HepBcAb), Hepatitis C antibody (HCVAb) or HIV.
11. Participants with a history of thromboembolic events.
12. Participants with a history of cyclic neutropenia.
13. History of TB or active, latent or inadequately treated TB infection.  All positive TB 
test result(s) are exclusionary.
Other exclusions
14. History of regular alcohol consumption exceeding 14 drinks/week for male
participants (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 
1.5 ounces [45 mL] of hard liquor) within 6 months before Screening.


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15. Use of tobacco or nicotine containing products in excess of the equivalent of 
5 cigarettes per day.
16. Exposure to live vaccines within the 28 days prior to the screening visit.
17. Treatment with an investigational drug within 30 days (or as determined by the local 
requirement) or 5 half-lives preceding the first dose of investigational product (IP)
(whichever is longer). An approved COVID-19 vaccine is considered a concomitant 
medication .  Due to the potential for interference with vaccine efficacy, the last dose 
of an approved COVID-19 vaccine must be completed 28 days prior to dosing with 
PF-06755347.
18. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest.  If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine the participants eligibility.
19. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval 
>450 msec or a QRS interval >120 msec.  If QTc exceeds 450 msec, or QRS exceeds 
120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or 
QRS values should be used to determine the participants eligibility.
20. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening or on admission, as assessed by the study specific laboratory and confirmed 
by a single repeat tests, if deemed necessary: 

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 
>1.25 × upper limit of normal (ULN);

Total bilirubin level >1.0 × ULN; participants with a history of Gilberts syndrome 
may have direct bilirubin measured and would be eligible for this study provided 
the direct bilirubin level is ≤ULN;

Creatinine levels >1.0 × ULN;

eGFR of <90 mL/min/1.73m2.
21. Male participants with partners currently pregnant; fertile male participants who are 
unwilling or unable to use a condom or whose female partners are unable or unwilling 
to use a highly effective method of contraception as outlined in this protocol for the 
duration of the study through final study release of the participant (inclusive of final 
extended immune follow-up visit, if required), or through at least 28 days after the 
last dose of IP (whichever is longer).
22. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to dosing. 


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23. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol. 
24. Participants who are 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 participants who are Pfizer employees, including their family 
members, directly involved in the conduct of the study.
25. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality (including 
prothrombin time [PT]/international normalized ratio [INR], partial thromboplastin 
time [PTT], Ddimer, fibrinogen, hematology and ionogram) 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.
Prior/Concomitant Therapy
26. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 
5 half-lives (whichever is longer) prior to the first dose of IP.  As an exception, 
acetaminophen/paracetamol may be used at doses of ≤1 g/day.  Limited use of 
nonprescription treatments that are not believed to affect participant safety or the 
overall results of the study may be permitted on a case-by-case basis following 
approval by the Sponsor. 
27. Herbal supplements must have been discontinued at least 28 days prior to the first 
dose of investigational product.
28. Due to the potential for interference with vaccine efficacy, the last dose of an 
approved COVID-19 vaccine must be at least 28 days prior to dosing with 
PF-06755347.
Prior/Concurrent Clinical Study Experience:
29. Participation in a previous cohort in the current study.
5.3. Inclusion Criteria for Participants with ITP 
1. Male and female participants ages 18-55 years at time of ICD signature. Female 
participants may be of non-childbearing or childbearing potential.
2. Diagnosis of Primary ITP.  ITP must be diagnosed in accordance with established 
guidelines.17,18

Persistent (>3 months and ≤12 months) OR Chronic (>12 months).
AND


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
Platelet count 30-75 x 109/L (inclusive) with criteria achieved on 2 qualifying 
counts 

The first platelet count must be taken within approximately 10 days prior to 
dosing. The second platelet count must be taken at the time of admission.

There must be at least 5 days between the 2 platelet counts 
3. Participants must have received and responded to IVIg or corticosteroids as treatment 
for ITP (response is defined as achievement of platelet count >50 x 109/L and 
doubling of platelet count from baseline).
4. Willing and able to comply with all scheduled visits, treatment plan, lab tests, 
lifestyle considerations and other study procedures. 
5. BMI of 17.5 to 30.5 kg/m2 and a total body weight >40 kg (88 lbs). 
6. Capable of giving informed consent, including compliance with requirements and 
restrictions in ICD and in the protocol.
5.4. Exclusion Criteria for Participants with ITP 
Medical Conditions:
1. Evidence or history of clinically significant hematological (other than ITP), renal, 
endocrine, metabolic, pulmonary, gastrointestinal, cardiovascular, hepatic, 
psychiatric, neurologic, or allergic disease (but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
2. Chest X-ray with evidence of current, active TB, previous inactive TB, general 
infections, heart failure, malignancy, or other clinically significant abnormalities. 
Chest x-ray must be taken at Screening or within 3 months prior to Screening and 
read by a qualified radiologist. 
3. Any bleeding event requiring medical evaluation or treatment in the 4 weeks prior to 
screening.
4. Any current bleeding event that, in the opinion of the investigator, requires treatment.
5. Scheduled or anticipated invasive procedures (eg, surgery, dental procedures) within 
28 days following PF-06755347 dosing.
6. Splenectomy within ≤180 days prior to PF-06755347 dosing or splenectomy planned 
during the period of the study.
Diagnostic Assessments:
7. Positive urine drug test.


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8. History of any active autoimmune disorder (other than ITP) or other conditions that
may compromise or impair the immune system (including but not limited to: Crohn’s 
Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, 
Graves’ disease, and asthma).
9. Participants with a history or current evidence from lab safety tests of clinically 
significant dyslipidemia in the opinion of the investigator. 
10. History of immune deficiency or current evidence of total IgG or total IgA deficiency.
11. History of allergic or anaphylactic reaction to any drug including immunoglobulin. 
12. Fever or skin rash within 7 days prior to dosing.
13. History of active infections within 28 days prior to the screening visit.
14. History of Hepatitis B, Hepatitis C or HIV or current positive results for any of the 
following serological tests - HBsAg, HBcAb, HCVAb or HIV. 
15. History of thromboembolic events.  For participants in the Czech Republic, see 
Appendix 12: Country Specific Requirements.
16. History of cyclic neutropenia.
17. Any evidence of latent or active tuberculosis infection.
18. Hemoglobin <9 g/dL.
19. Positive Direct Coombs test.
Other Exclusions:
20. History of regular alcohol consumption for male participants exceeding 
14 drinks/week and for female participants, 7 drinks/week (1 drink = 5 ounces 
[150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard 
liquor) within 6 months before Screening.
21. Male participants with partners currently pregnant; fertile male participants who are 
unwilling or unable to use a condom or whose female partners are unable or unwilling 
to use a highly effective method of contraception as outlined in this protocol for the 
duration of the study through final study release of the participant (inclusive of final 
extended immune follow-up visit, if required), or through at least 28 days after the 
last dose of study intervention (whichever is longer).
22. Pregnant female participants; breastfeeding female subjects; and female participants 
of childbearing potential who are unwilling or unable to use a highly effective method 
of contraception as outlined in this protocol for the duration of the study through final 
study release of the participant (inclusive of final extended immune follow up visit, if 


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required), or through at least 28 days after the last dose of study intervention 
(whichever is longer).
23. Exposure to live vaccines within the 28 days prior to the screening visit.
24. Treatment with an investigational drug within 30 days (or as determined by the local 
requirement) or 5 half-lives preceding the first dose of IP (whichever is longer). 
a.
An approved COVID-19 vaccine is considered as a concomitant medication. Due 
to the potential for interference with vaccine efficacy the last dose of an approved 
COVID-19 vaccine must be completed 28 days prior to dosing with 
PF-06755347.
25. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest.  If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine participant eligibility.
26. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval
>450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 
120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or 
QRS values should be used to determine participant eligibility.
27. ANY of the following abnormalities in clinical laboratory tests at screening or on 
admission, as assessed by the study-specific laboratory and confirmed by a single 
repeat tests, if deemed necessary:

AST or ALT ≥1.5 x upper limit of normal); If currently taking eltrombopag, AST 
or ALT >3 × ULN;

Total bilirubin ≥1.25 x upper limit of normal); If currently taking eltrombopag,  
total bilirubin level >1.5 × ULN (Participants with a history of Gilberts syndrome 
may have direct bilirubin measured and would be eligible for this study provided 
the direct bilirubin level is ≤ULN);

Serum creatinine >1.5 x ULN;

eGFR <60 ml/min/1.73m2 by CKD-EPI Formula.
28. Participants who are 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 participants who are Pfizer employees (including their family 
members) directly involved in the conduct of the study.


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29. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
30. Participation in a previous cohort in the current study.
Prior/Concurrent Therapy for ITP:
31. ≤28 days prior to PF-06755347 dosing: 

Treatment with IVIg or an anti-Rh D antigen agent (eg, WinRho®).

Treatment with high-dose pulse corticosteroid therapy (eg, dexamethasone 
40mg/day for 4 days or methylprednisolone 30 mg/kg/day for 3 days).

Other Anti-inflammatory Drugs, including NSAIDS for Cox-1 and Cox-2 
(eg, Ibuprofen, naproxen, aspirin, diclofenac) or anti-IL-6 agents tocilizumab or 
siltuximab.
32. Within 3 months prior to PF-06755347 dosing: 

Treatment with cytotoxic agents (eg, cyclophosphamide, vincristine).

Plasmapheresis.
33. Within 6 months prior to PF-06755347 dosing: 

Treatment with rituximab (or any other anti-CD20 agent).
Concomitant Therapy:
34. If receiving corticosteroids, the dose must be <1 mg/kg prednisone per day or 
equivalent, must have been stable or decreasing for ≥28 days prior to PF-06755347 
dosing and must be expected to remain stable or to decrease for the duration of the 
study.
35. If receiving any of the medications shown below, the dose must have been stable for 
≥28 days prior to PF-06755347 dosing and must be expected to remain stable for the 
duration of the study: 

Avatrombopag, eltrombopag, fostamatinib, or romiplostim.

Adjunct immunosuppressives cyclosporine, azathioprine, mycophenolate, or 
6-mercaptopurine.


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5.5. Lifestyle Considerations
The following guidelines are provided:
5.5.1. Meals and Dietary Restrictions

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations (minimum of 12 hrs for lipid profile at 
screening). Participants will not be required to fast on Day 1 for post-dose laboratory 
safety tests. Water may be consumed without restriction throughout the study. 

On dosing days, a standard breakfast will be provided approximately 1 hour prior to 
the start of dosing and last approximately 20 minutes.  Standard breakfast will be 
provided on other in-patient stay days.

Lunch will be provided approximately 4 hours after the start of dosing.

Dinner will be provided approximately 9 to 10 hours after the start of dosing.

An evening snack may be permitted.

While confined, the total daily nutritional composition should be approximately 
55% carbohydrate, 30% fat and 15% protein.  The daily caloric intake per participant
should not exceed approximately 3200 kcal.
5.5.2. Caffeine, Alcohol and Tobacco

Participants will abstain from alcohol for 24 hours prior to admission and continue 
abstaining from alcohol until discharge, as well as 24 hours prior to outpatient visits.  
Participants may undergo an alcohol breath, blood or urine test at the discretion of the 
investigator.

Healthy participants will abstain from caffeine-containing products for 24 hours prior 
to the start of dosing or until collection of the final PK sample prior to discharge on 
Day 8. Caffeine is allowed for participants with ITP.

Healthy participants will abstain from the use of tobacco- or nicotine-containing 
products for 24 hours prior to dosing and during confinement in the research unit. 
Nicotine-containing products are allowed for participants with ITP.
5.5.3. Activity

Participants will be confined to the procedure room/participant room, as appropriate, 
for the first 8 hours after the start of dosing on Day 1 during continuous cardiac 
monitoring, except for lunch and to use the bathroom.  After this, if the equipment 
setup allows, participants may be ambulatory during the continuous cardiac 
monitoring period, but should not engage in strenuous activities.  If equipment does 
not allow ambulation, appropriate accommodations will be made by the investigator 


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site to facilitate continuous monitoring (eg, bedside urinals should be provided to 
accommodate participants’ excretory needs).

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests.  Walking at a normal pace will be permitted.
5.5.4. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his/her partner(s) from the permitted list of contraception methods (see
Appendix 4) and will confirm that the participant has been instructed in its consistent and 
correct use.  At time points indicated in the SoA, the investigator or designee will inform the 
participant of the need to use highly effective contraception consistently and correctly and 
document the conversation and the participants affirmation in the participants chart 
(participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or the participant’s partner.
5.6. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to investigational product/entered in the study.  
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 once and must meet all inclusion/exclusion criteria.  Rescreened participants will 
be re-consented. All screening assessments must be repeated during rescreening.
6. STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
For this study, the investigational product is PF-06755347 and its non-matching placebo.
PF-06755347 and non-matching placebo will be supplied by Pfizer as solution for injection 
in sterile vials for preparation of intravenous infusion and subcutaneous injections at the
study site. 


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PF-06755347 1000 mg/vial Solution for Injection (50 mg/mL) is presented as a sterile 
solution for intravenous and subcutaneous administration.  Each vial of PF-06755347 
contains a sufficient amount of product to ensure an extractable volume of 20 mL of aqueous 
buffered solution, is sealed with a coated stopper and an overseal, and is labeled according to 
local regulatory requirements. 
Placebo for PF-06755347 Solution for Injection is presented as a sterile solution for 
intravenous and subcutaneous administration.  Each vial contains 20 mL of placebo as an 
aqueous buffered solution, is sealed with a coated stopper and an overseal, and is labeled 
according to local regulatory requirements. 
Sterile vials will be supplied as individual vials packaged in an open-label fashion in units of 
multiple vials in a carton.
6.1.1. Administration
Healthy Participants
Participants will start receiving IP in a blinded fashion at approximately 08:00 hours (plus or 
minus 3 hours). Blinded investigator site personnel will administer IP for each participant 
according to the IP Manual. The IV infusion will be on the opposite arm from PK sampling 
and start and stop time of the infusion will be recorded. The preferred site for subcutaneous 
injection(s) will be on the abdomen.
Participants with ITP
Participants will receive open-label IP at approximately 08:00 hours (plus or minus 3 hours). 
Investigator site personnel will administer IP for each participant according to the IP Manual. 
The preferred site for subcutaneous injection(s) will be on the abdomen.
6.1.1.1. Guideline on Intravenous Infusion
PF-06755347 or placebo will be administered by continuous IV infusion.  The infusion rate 
and duration depends on the dose and the volume to be infused.  Table 8 provides guidelines 
on infusion scheme for each proposed dose; however the actual infusion rate may be lowered
and/or infusion duration may be increased to mitigate infusion-related symptoms at the 
discretion of the PI (see Section 6.6 and Section 6.7).  The overall infusion time will not
exceed 4 hrs. The infusion scheme will also be adjusted appropriately if doses other than 
those proposed are used. 


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Table 8.
Guideline on Intravenous Infusion Scheme
Target 
Dose 
(mg/kg)
Infusate Drug 
concentration
(mg/mL)
Infusion Rate
(mL/kg/min)
Dosing
Rate
(mg/kg/min)
Infusion 
Durationc(min)
Dose per 
Interval
(mg/kg)
0.01
0.03
0.006
0.00018
60
0.01
0.03
0.03
0.017
0.00051
60
0.03
0.1
0.05
0.02
0.001
30
0.03
0.05
0.04
0.002
35
0.07
0.3
0.15
0.02
0.003
30
0.09
0.15
0.04
0.006
35
0.21
1a
0.5
0.02
0.01
30
0.3
0.5
0.04
0.02
35
0.7
1b
0.5
0.011
0.0055
180
1
2
0.5
0.022
0.011
180
2
4
1.5
0.015
0.023
180
4
8
1.5
0.03
0.045
180
8
16
2.5
0.036
0.09
180
16
a.
Infusion rates for the first 3 participants in Cohort 5 (1 mg/kg IV).
b.
Infusion rates for the 4 participants in Cohort 5 (1 mg/kg IV) expansion.
c.
Infusion duration of 180 minutes (±18 minutes).
6.1.1.2. Guideline on Subcutaneous Injection
For participants receiving a SC injection, the number of injections will be recorded. Time 0 
for the SC injection will be the time of the first injection. The preferred body location for the 
SC injection is the abdomen but the 5 cm area around the navel should be avoided. If 
abdominal injections are not possible, arm or thigh locations may also be used. If an arm is 
used for the SC injection, the opposite arm should be used for the PK blood sample 
collections. For doses that require more than one injection, individual injections should be 
administered approximately 3 cm away from the site of the previous injection (ie, the 
abdomen, same arm or thigh). Avoid umbilicus area and skin with tattoos and scarring. The 
maximum volume for an individual injection is 1.5 ml.  Since the drug product concentration 
is 50 mg/mL, the maximum number of injections will be approximately 4. At SC doses that 
require greater than the maximum number of injections, a SC infusion will be used.
If a participant experiences an infusion or injection site reaction during the administration
period, then treatment administration should be paused for that participant and supportive 
care should be provided according to the Investigator’s standard practice (eg, treatment with 
an antihistamine). Treatment administration may resume at the discretion of the Investigator 
if there are no systemic symptoms and if the reaction resolves. 
Consult the IP Manual for detailed instructions regarding study drug preparation, stability 
and administration. Per the drug stopping rules (Section 6.6 and Section 6.7), dosing will be 
paused for the entire cohort, for any serious adverse event (SAE) that occurs in a participant
receiving active treatment until causality is fully assessed by the PI and Sponsor.


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6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention, as 
applicable for temperature-monitored shipments. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperature since previously documented for all 
site storage locations upon return to business.
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records).  All study 
interventions will be accounted for using an investigational product accountability 
form/record.  
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
6. Study interventions should be stored in their original containers and in accordance 
with the labels. 
7. See the IP Manual for storage conditions of the study intervention once prepared. 
8. Deviations from the storage requirements, including any actions taken, must be 
documented and reported to Pfizer upon discovery.  The site should actively pursue 
options for returning the study intervention to the storage conditions described in the 
labeling, as soon as possible.  Once an excursion is identified, the study intervention
must be quarantined and not used until Pfizer provides permission to use the study 
intervention.  It will not be considered a protocol deviation if Pfizer approves the use 
of the study intervention after the temperature excursion. Use of the study 
intervention prior to Pfizer approval will be considered a protocol deviation. Specific 
details regarding the definition of an excursion and information the site should report 
for each excursion will be provided to the site in the IP manual.


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9. The Sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the investigational product ready for administration or dispensing to the participant by 
qualified staff.  Dispensing is defined as the provision of investigational product, 
concomitant treatments, and accompanying information by qualified staff member(s) to a 
healthcare provider or participant in accordance with this protocol.  Local health authority 
regulations or investigator site guidelines may use alternative terms for these activities. 
See the IP Manual for instructions on how to prepare and blind the investigational product 
for administration.  
PF-06755347 and placebo should be prepared by an appropriately qualified unblinded site 
personnel (ie, pharmacist) according to the IP manual 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. Dose preparation must be performed with locally 
accepted sterile handling technique and the investigational product will be administered in 
blinded fashion to the participant.
PF-06755347 and placebo vials are single use.
All dosing and administration calculations and dose preparation must be performed and 
checked by one qualified clinical site personnel and verified by a qualified and experienced 
second clinical site personnel (eg, physician, nurse, physician’s assistant, nurse practitioner, 
pharmacy assistant/technician, or pharmacist). The site will take all necessary precautions to 
maintain the investigator and other site personnel blind.
6.3. Measures to minimize bias: Randomization and blinding
An Interactive Response Technology (IRT) system will be programmed with blind-breaking 
instructions. Refer to subsections 6.3.1 Allocation to Investigational Product and 6.3.2
Breaking the Blind for further details.
6.3.1. Allocation to Investigational Product
Allocation of participants to treatment groups will proceed through the use of an interactive
response technology (IRT) system (interactive Web-based response [IWR]). The site
personnel (study coordinator or specified designee) will be required to enter or select
information including but not limited to the user’s identification (ID) and password, the
protocol number, and the participant number. The site personnel will then be provided with a


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treatment assignment and randomization number, when investigational product is being 
supplied via the IRT system. The IRT system will provide a confirmation report containing 
the participant number, randomization number, and treatment assignment.. The confirmation 
report must be stored in the site’s files.
Investigational product will be dispensed at Day 1 inpatient visit.
The study-specific IRT reference manual and IP manual will provide the contact information
and further details on the use of the IRT system.
6.3.2. Breaking the Blind (for HP cohorts only)
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process. The IRT will be programmed
with blind-breaking instructions. In case of an emergency, the investigator has the sole
responsibility for determining if unblinding of a participant’s treatment assignment is
warranted. Participant safety must always be the first consideration in making such a
determination.
If the investigator decides that unblinding is warranted in the interest of the safety of a 
participant, the investigator should make every effort to contact the Sponsor prior to 
unblinding a participant’s treatment assignment unless this could delay further management 
of the participant. However, discussion with the Sponsor in advance of unblinding is not 
required. If a participant’s treatment assignment is unblinded, the Sponsor must be notified 
within 24 hours after breaking the blind.
When the blinding code is broken, the reason must be fully documented and entered on the 
data collection tool (DCT).
Blood specimens will be obtained from all participants for PK analysis to maintain the study 
blind at the investigator site.  The investigator site staff and blinded study monitor, if 
assigned, will be blinded to IP.  A designated limited number of Sponsor colleagues within 
the study team will be unblinded to participant treatments in order to permit real-time
interpretation of the safety and PK data and provide information necessary to potentially alter 
the dose-escalation sequence (see Section 9.9).  Specimens from participants randomized to 
placebo will not be routinely analyzed.  To minimize the potential for bias, treatment 
randomization information will be kept confidential by Pfizer unblinded personnel and will 
not be released to the blinded investigator or blinded investigator site personnel until the 
study database has been locked or the investigator requests unblinding for safety reasons. 
6.4. Study Intervention Compliance
The site will complete the required dosage Preparation Record located in the IP manual.  The 
use of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system.  The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose.  This may be used in place of the Preparation Record after 
approval from the Sponsor and/or designee.


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6.5. Concomitant Therapy
Healthy participants will abstain from all concomitant therapies except those required for the 
treatment of adverse events.
Participants with ITP will be permitted to continue any medications that they routinely 
receive for treatment of ITP or any other co-existing medical conditions, so long as their use 
does not violate any inclusion or exclusion criteria. They will also be permitted to receive 
concomitant therapies required for the treatment of adverse events. 
Acetaminophen/paracetamol, nonsteroidal anti-inflammatory drugs (for HPs only) and 
diphenhydramine  are permitted to manage adverse events and infusion or injection related
reactions. 
Limited use of nonprescription treatments that are not believed to affect participant safety or 
the overall results of the study may be permitted on a case-by-case basis following approval 
by the Sponsor.
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  All participants will be questioned about 
concomitant treatment at each clinic visit.
Treatments taken within 56 days before the first dose of investigational product will be 
documented as a prior treatment.  Treatments taken after the first dose of investigational 
product will be documented as concomitant treatments.
6.5.1. Rescue Medication
6.5.1.1. Rescue Therapy for CRS
Rescue therapy for CRS should be immediately available including oral paracetamol, oral 
NSAIDs, IV normal saline, IV corticosteroids, oxygen.
An ICU should be available for additional support and administration of vasopressors if 
appropriate. The availability of anti-IL-6 agents is optional.
See Section 10.10 for further guidance.
6.5.1.2. Rescue Therapy for Bleeding Events in ITP Participants  
Rescue therapy for bleeding events in ITP participants should be carried out in accordance 
with each country’s/site’s standard procedures and practices.19
6.6. Dose Progression
The participants within each cohort will be dosed using a sequential dosing scheme. For all 
cohorts, a single participant will be dosed at a given time, followed by a minimum of 72-hour 
(for IV) and 96-hours (for SC) safety monitoring period. In total there will be a minimum of 
96 hours between each IV participant dosed and 120 hours for each SC participant dosed. 


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The following rules will be applied when considering dosing of the next participant in the 
cohort.
Sequential dosing may proceed only if no adverse events are reported OR all of the 
following criteria are met:
1. Any pro-inflammatory events are < Grade 2 Per CTCAE criteria in Appendix 9.
2. All other adverse events are deemed mild or moderate in severity, regardless of 
relatedness.
3. Any laboratory, ECG or vital sign changes are considered not clinically significant.
4. No other pause or stop criteria are met.
5. For participants with ITP, in addition to the above  criteria, no participant has greater 
than a 30% decrease in platelet count – defined from the immediate pre-dosing 
platelet count to the lowest postdosing platelet count.  Dose progression will be 
independent of dose progression from HP cohorts at higher dose levels.
Sequential dosing should be paused if any criterion below is met in a participant receiving 
active drug: 
1. Grade 2 (Objective) pro-inflammatory event (vomiting, diarrhea, hypotension or 
hypoxia) (see Appendix 9).
2. Adverse event which is considered to be severe (Grade 3 or higher) AND is deemed 
related to study intervention.
3. A moderate event (Grade 2) AND is deemed related to study intervention not 
otherwise identified as a proinflammatory event or AE of special interest, that in the 
opinion of the PI and Sponsor are of concern and warrant further investigation before 
additional dosing.
4. For participants with ITP, platelet count of <30 x 109/L AND a decrease from 
baseline ≥30%, or a platelet count decrease from baseline of ≥50%, defined from the 
immediate pre-dosing platelet count to the lowest post-dosing platelet count, or a 
bleeding or bruising-related AE CTCAE 4.03 Grade 2 or higher (except metrorrhagia 
Grade 3 or higher).
Sequential dosing should be stopped at the current dose level if any criterion below is met in 
participant receiving active drug:
1. Grade 3 or greater pro-inflammatory event.
2. Serious adverse event that is deemed related to study intervention.  


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3. A single occurrence of confirmed drug induced liver injury (see Appendix 6) or 
confirmed drug induced kidney injury (see Section 7.1) will be reported as a serious 
adverse event, and therefore, will be considered dose limiting.
In the event of a dose pause, all available safety, PK (if available), cytokine, and 
complement data for the participants will be reviewed by the dose escalation subteam. The 
subteam should determine whether clinical symptoms associated with the pause criteria have 
resolved and determine whether IL-6 has returned to near baseline levels ie that the event is 
reversible. IL-6 has been selected as the surrogate marker for decision making purposes as it 
appears to be the most sensitive cytokine pathways from the non-human primate and human 
in vitro data. However, TNF-, IFN-cytokine and complement data will be available at the 
time of review. If the dose escalation subteam determines that dosing may resume, a plan 
that mitigates risks to participants with the resumption of dosing may be implemented.  Such 
a plan could include a revision of inclusion/exclusion criteria, repeating or reducing the dose, 
reducing infusion/dosing rate or adding appropriate safety monitoring or prophylactic 
treatment. This mitigation plan may need to be discussed with the Institutional Review 
Board (IRB) or Regulatory Authority as appropriate. The ultimate decision to continue 
dosing of study participants rests with the PI.  Sponsor dose escalation subteam cannot 
overrule PI decision/clinical judgement.
If the decision is to stop dose progression this will also stop any further dose escalation.
6.7. Dose Escalation
After each cohort has completed, a batched level review of all available safety, PK, cytokine 
and complement data will occur. For purposes of dose escalation, a completer is defined as a 
participant that has finished the clinical confinement up to Day 8. Dose escalation can 
proceed if the last dose was considered to be safe and well tolerated in all participants up to 
Day 8. Dose escalation may be stopped if it is determined that the limits of safety and/or 
tolerability or PK stopping criteria have been reached.  This decision will be made after a 
discussion takes place between the Sponsor study team and each site’s investigator or 
delegate.  The Sponsor study team may not overrule the investigators decision to stop dose 
escalation.  If dose escalation is stopped because of any of these criteria, additional cohorts 
may receive the same or lower doses of the investigational product.
Dose escalation may progress when one of the following criterion is met:

Sequential dosing was completed successfully for the cohort and the last dose was 
considered to be safe and well tolerated.

In the event that a dosing pause criteria has been met for the cohort (see Section 6.6), 
the dose escalation subteam confirmed that, after review of all data, it is safe to 
progress. Any requested mitigations must be applied eg, reduction in infusion rate. 

Dose escalation from the first to second ITP cohort will occur when the first dose is 
deemed safe and tolerable in ITP participants AND the second ITP cohort dose is 
deemed safe and tolerable in HPs, ie, dependent upon HP data. 


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For sites in the Czech Republic, the participation of females with ITP should commence only 
following approval by the Sponsor’s dose escalation subteam. Please refer to Appendix 12: 
Country Specific Requirements for further details. 
The dose escalation will be terminated if any of the following criterion is met:

If 50% or more of the participants receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar clinically significant laboratory, ECG, 
or vital sign abnormalities, in the same organ class, indicating dose-limiting 
intolerance.

Severe nonserious AEs, considered as, at least, possibly related to study intervention 
administration, in 2 participants at a given dose level (but not participants receiving 
placebo), independent of within or not within the same system organ class, indicating 
dose limiting intolerance.

It is determined that the limit of safety and/or tolerability has been reached.  This 
decision will be made following discussions between the study team and the 
investigator.

Other findings that, at the discretion of the study team and investigators, indicate that 
dose escalation should be halted.

Sequential dosing was stopped based on the criteria in Section 6.6. 

At any dose level, the exposure reaches or exceeds the PK stopping limits in any 
individual participant (AUC168 of 34000 µg·hr/mL and/or Cmax of 1130 µg/mL).

Based on the observed data, the Cmax or AUC168 of the next planned dose is projected 
to exceed the escalation limits in any individual participant, that dose will not be 
explored.  Modified doses may be explored if they are not expected to exceed PK 
stopping criteria.
If following an internal safety review, it is appropriate to restart the trial, a substantial 
amendment will be submitted to CAs and ECs.  The trial will not restart until the amendment 
has been approved by CAs and ECs.
Progression to the next dose will occur if the last dose was well tolerated and after 
satisfactory review of the available safety and PK data.
6.8. Infusion or Injection Site Reactions (ISR)
ISR is a type of hypersensitivity reaction that may be immediate, although it usually appears 
within 24-48 hrs after injection. ISR, by definition, includes the following: erythema, 
induration ecchymosis, pain and pruritus at the infusion or injection site.  


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Infusion or injection-related reactions will be assessed and managed based on the CTCAE
severity scale for infusion reactions (see Appendix 11). 

Grade 1 reaction (Mild): Participant will be monitored closely at bedside while 
infusion or injection continues.  For IV dosing, the PI may slow the infusion rate, 
based on medical judgement.

Grade 2 (Moderate): Infusion may be paused, and symptomatic treatment (such as 
antihistamine, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) 
may be administered.  For IV dosing, if the infusion is paused, once symptoms 
subside, infusion may be restarted at a 50% reduction in infusion rate.  Infusion rate 
may be increased after 30 minutes if participant is stable. 

Grade 3 (Severe) or 4 (life-threatening): FoIV dosing, the infusion will be stopped 
promptly.  Participant will be followed until symptoms resolve, and no further 
follow-up regarding the AEs is needed in the opinion of the PI. 

For IV dosing, acute infusion reactions of mild-moderate severity (Grade 1 or 
Grade 2) which fully resolve following dose interruption and/or the administration of 
antihistamines/antipyretics with subsequent resumption and safe completion of dosing 
will not be considered dose limiting.
6.9. 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
Discontinuation of Study Intervention
Potential Cases of Acute Kidney Injury
Abnormal values in serum creatinine (SCr) concurrent with presence or absence of increase 
in blood urea nitrogen (BUN) that meet the criteria below, in the absence of other causes of 
kidney injury, are considered potential cases of acute kidney injury and should be considered 
important medical events. 
An increase of ≥0.3 mg/dL (or ≥26.5 µmol/L) in SCr level relative to the participants own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness.
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 µmol/L] in SCr
relative to the participants own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 µmol/L), 
adequate, immediate, supportive measures taken to correct apparent acute kidney injury.


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Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result.  This evaluation should include laboratory tests, detailed history, and physical 
assessment.  In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices.  Continued follow-up per protocol as well as any additional 
specific investigations/management required to manage the kidney injury is required until 
resolution.
All cases confirmed on repeat testing as meeting the laboratory criteria for acute kidney 
injury, with no other cause(s) of laboratory abnormalities identified, should be considered 
potential cases of drug-induced kidney injury irrespective of availability of all the results of 
the investigations performed to determine etiology of the abnormal SCr.  If ≥2 healthy 
participants in a given cohort are noted to have 2 consecutive SCr results of ≥0.3 mg/dL (or
≥26.5 µmol/L), an assessment of whether the finding may be considered an adverse drug 
reaction should be undertaken.
7.1. 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.
If a participant discontinues during the trial, the participant may be replaced at the discretion 
of the Sponsor in consultation with the PI.  
At the time of discontinuing from the study, if possible, an early termination visit with 
assessments from Day 71 should be conducted.  See the SoA for assessments to be collected 
at the time of study discontinuation and follow-up and for any further evaluations that need 
to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study.  Participants should be questioned regarding 
their reason for withdrawal.  The participant will be permanently discontinued both from the 
study intervention and from the study at that time.
If a participant withdraws from the study, he 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 7.1.1) 
for disclosure of future information, no further evaluations should be performed, and no 
additional data should be collected.  The Sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participants safety was preserved.
7.1.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or persons previously authorized by the participant to provide this information.  
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible.  The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate case report form (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.
7.2. Lost to Follow up 
A participant will be considered lost to follow-up if he repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participants last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant’s medical record;

Should the participant continue to be unreachable, he 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.


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8. STUDY ASSESSMENTS AND PROCEDURES
Participants will be screened within 56 days prior to administration of the investigational 
product to confirm that they meet the study population criteria for the study.  The investigator 
(or an appropriate delegate at the investigator site) must obtain a signed and dated ICD 
before performing any study-specific procedures.  
A participant who qualified for this protocol but did not enroll from an earlier cohort/group 
may be used in a subsequent cohort/group without rescreening, provided laboratory results 
obtained prior to the first dose administration meet eligibility criteria for this study.  In 
addition, other clinical assessments or specimen collections, eg, banked biospecimens, may 
be used without repeat collection, as appropriate.
Study procedures and their timing are summarized in the SoA.  Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter or if not, ensure 
adequate rest is achieved prior to the collection of vital signs. 
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.
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.


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8.1. Efficacy Assessments
Not Applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, assessment of head, ears, eyes, 
nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, 
musculoskeletal, and neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant reported symptoms. 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. 
Height and weight will also be measured and recorded as per the SoA.  For measuring 
weight, a scale with appropriate range and resolution is used and must be placed on a stable, 
flat surface. Participants must remove shoes, bulky layers of clothing, and jackets so that 
only light clothing remains.  They must also remove the contents of their pockets and remain 
still during measurement of weight.
8.2.2. Vital Signs
Supine BP will be measured with the participants arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study. Blood pressure should be 
taken from the contralateral arm to that receiving infusion.  Participants should be instructed 
not to speak during measurements.
The same properly sized and calibrated BP cuff will be used to measure BP each time.  The 
use of an automated device for measuring BP and pulse rate is acceptable, however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds.  When the timing of these measurements coincides with a blood collection, BP
and pulse rate should be obtained prior to the nominal time of the blood collection.
Triplicate vital signs measurement (including oral temperature) at the times specified in the 
SoA should be collected approximately 2 minutes apart.
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data.


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Normal range for vital sign measurements are defined as: 90 mmHg ≤systolic BP
≤139 mmHg; 50 mmHg ≤diastolic BP ≤89 mmHg; 40 bpm ≤heart rate ≤100 bpm; 
35.4°C ≤oral temperature ≤37.5°C.
8.2.2.1. Respiratory Rate
Not Applicable.
8.2.2.2. Temperature
Temperature will be measured using either an oral or tympanic method.  The same collection 
method for each participant is required throughout the study. No eating and drinking is 
allowed for 15 minutes prior to the measurement.
8.2.3. Electrocardiogram
Standard 12-Lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex.  Alternative lead placement methodology using torso leads (eg, Mason-Likar) is not 
recommended given the potential risk of discrepancies with ECGs acquired using standard 
limb lead placement. All scheduled ECGs should be performed after the participant has 
rested quietly for at least 10 minutes in a supine position. 
Triplicate 12-lead ECGs will be obtained approximately 2 to 4 minutes apart; the average 
QTc value from the triplicate ECG measurements collected at each nominal time point on 
Day -1 will serve as each participant’s time-controlled baseline QTc value.
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements.  Additional ECG monitoring will occur if a) the 
mean value from the triplicate measurements for any postdose QTc interval is increased by
≥30 msec from the baseline and is >450 msec; or b) an absolute QTc value is ≥500 msec for 
any scheduled ECG.  If either of these conditions occurs, then a single ECG measurement 
must be repeated at least hourly until QTc values from 2 successive ECGs fall below the 
threshold value that triggered the repeat measurement.
If a postdose QTc interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator), or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator). 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 


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qualified medical providers interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.3.1. Continuous Cardiac Monitoring by Telemetry
All abnormal rhythms will be recorded and reviewed by the study physician for the presence 
of rhythms of potential clinical concern.  The time, duration, and description of the clinically 
significant event will be recorded in the DCT.  In addition, a printed record of the tracing(s) 
of the clinically significant rhythm(s) will be made and retained with other source 
documents.
Telemetry should be collected using a centralized system that also allows for the storage and 
advanced analysis of all recorded data in order to preserve important events for future 
evaluations.  Holter monitoring should not be used in parallel with continuous telemetry, 
unless it is the only means of data storage available at the investigator site, or verifiable 
arrhythmia quantification is required.  To establish a baseline, telemetry should be recorded 
for at least 2 hours before dosing.  This may be done immediately prior to dosing or at some 
2-hour continuous interval between admission and prior to dosing, as long as the recording is 
performed when the participant is awake.  Telemetry may be stopped within a reasonably 
short period of time prior to dosing, in order to avoid interference with study operations 
conducted immediately before dosing.  However, it is expected that the telemetry leads will 
be in place and the system connected prior to dosing.
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.  All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.  
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study 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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See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.5. Pulse Oximetry
Saturation level of oxygen in blood (Sp02) will be measured as outlined in the SoA using 
Pulse Oximetry and can be obtained in a supine position.  Additional collection times, or 
changes to collection times will be permitted, as necessary, to ensure appropriate collection 
of safety data.
8.2.6. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior to the participant’s receiving PF-06755347. Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study. Pregnancy tests may also be 
repeated if requested by IRBs/ECs or if required by local regulations. If a urine test cannot 
be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In 
such cases, the participant must be excluded if the serum pregnancy result is positive.
8.3. Adverse Events and Serious Adverse Events
The definition 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 participants 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 (see Section 7). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
Assessment of adverse events will include the type, incidence, severity (CTCAE version 
4.03, Appendix 11) timing, seriousness, and relatedness for injection site reactions.  The 
severity of CRS will be assessed according to the grading described by the ASTCT and Lee 
et al. (2019, see Appendix 10).12


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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 participants participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 28 calendar days, except as indicated below, after the last administration of the 
investigational product.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AE or SAE 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 or study participation, the investigator must 
promptly notify the Sponsor.
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 and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3.  The 
investigator will submit any updated SAE data to the Sponsor within 24 hours of it being 
available.
SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Non-serious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.


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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.2).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs)/ ECs, and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the Sponsor will review and then file it along with the investigators 
brochure and will notify the IRB/EC, if appropriate according to local requirements.


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8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure.  Below are examples of 
environmental exposure during pregnancy:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation, or skin contact then exposes his female partner 
prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred.  The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP
Supplemental Form, regardless of whether an SAE has occurred.  Details of the 
pregnancies will be collected after the start of study intervention and until at least 
5 terminal half-lives after the last dose.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form.  Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 


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integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs.  If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly [in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death]), the investigator should follow the procedures 
for reporting SAEs.  Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the Sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure).  An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.  
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred.  The 
information must be reported using the CT SAE Report Form.  When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF.  However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.


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An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use.  However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, 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.
The investigator must report occupational exposure 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
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
All adverse events of special interest (AESIs) must be reported as an AE or SAE following 
the procedures described in Section 10.3.  An AESI is to be recorded as an AE or SAE on the 
CRF.  In addition, an AESI that is also an SAE must be reported using the CT SAE Report 
Form.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength, or 
noncompliance as described in Section 6.4.  
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.


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Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the Sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on 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 investigational product greater than that prescribed at each dose 
level will be considered an overdose.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-06755347 (whichever 
is longer).
3. Obtain a blood sample for PK analysis within 2 days from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
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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 PF-06755347
Blood samples (2 mL) to provide approximately 0.5 mL plasma for pharmacokinetic analysis 
will be collected into appropriately labeled tubes containing dipotassium ethylene diamine 
tetraacetic acid (K2EDTA) at times specified in the SoA. 
The actual times may change but the number of samples will remain the same.  All efforts 
will be made to obtain the pharmacokinetic samples at the exact nominal time relative to 
dosing.  However, samples obtained within 10% of the nominal time (eg, within 6 minutes of 
a 60 minute sample) from dosing will not be captured as a protocol deviation, as long as the 
exact time of the sample collection is noted on the source document and data collection tool 
(eg, DCT). Collection of samples more than 10 hours after dose administration that are
obtained ≤1 hour away from the nominal time relative to dosing will not be captured as a 
protocol deviation, as long as the exact time of the collection is noted on the source 
document and data collection tool (eg, DCT). This protocol deviation window does not 
apply to samples to be collected more than 10 hours after dose administration at 
outpatient/follow-up visits with visit windows.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity.  Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the Sponsor.  
On a case-by-case basis, the Sponsor may make a determination as to whether sample 
integrity has been compromised.  Any deviation from the specified sample handling 
procedure resulted in compromised sample integrity will be considered a protocol deviation.
As part of understanding the pharmacokinetics of the IP, samples may be used for metabolite 
identification and/or evaluation of the bioanalytical method, 
 
  These data will not be included in the clinical study report (CSR). 
8.5.2. Analysis of Anti-Drug Antibodies 
Blood samples (4 mL) to provide approximately 1.5 mL serum for the assessment of antidrug 
(anti-PF-06755347) antibodies will be collected into appropriately labeled tubes containing 
no anticoagulant or gel serum separator at visits specified in the SoA. 
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The ADA sample analysis will follow a tiered approach of screening, confirmation, and titer 
determination.  Samples will be analyzed using a validated analytical method in compliance 
with Pfizer standard operating procedures.
The ADA samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity.  Any deviations from the immunogenicity 
sample handling procedure (eg, sample collection and processing steps, interim storage or 
shipping conditions), including any actions taken, must be documented and reported to the 
Sponsor.  On a case-by-case basis, the Sponsor may make a determination as to whether 
sample integrity has been compromised.  Any deviation from the specified sample handling 
procedure resulting in compromised sample integrity will be considered a protocol deviation.
 
 
  
 
  
 
 
 
 
 
  
 
 
  
 
  
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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. Statistical Hypotheses
No formal statistical hypothesis testing will be performed in this study. 
9.2. Sample Size Determination
No formal sample size calculation was performed.  For cohorts that include healthy 
participants, cohort size of approximately 4 (3 active, 1 placebo) to 8 (4 active, 2 placebo)
participants has been chosen to ensure appropriate sample size to provide adequate safety, 
toleration and PK information at each dose level and to provide a placebo comparison group, 
while minimizing exposure to humans of a new biologic entity.  ITP Cohorts  will not 
include placebo. ITP cohort size will be approximately 3 to 6 participants to reflect the 
number dosed receiving PF-06755347 in HP cohorts. Participants who discontinue during 
the trial may be replaced at the discretion of the Sponsor and Investigator.
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9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICD.
PK Population
The PK concentration population is defined as randomized 
participants who received at least one dose and have at least 
1 concentration.
The PK parameter analysis population is defined as all 
randomized participants who received at least one dose and 
have at least 1 of the PK parameters of interest.
PD Population
The PD analysis population is defined as all randomized 
participants treated who have at least one PD assessment in at 
least one cohort.
Safety
All participants randomly assigned to investigational product 
and who receive at least 1 dose of investigational product.  
Participants will be analyzed according to the product they 
actually received.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.
9.4.1. Efficacy Analyses
An efficacy analysis is not applicable to this study. 
9.5. Pharmacokinetic Analysis
9.5.1. Derivation of Pharmacokinetic Parameters
PK parameters following single dose administration will be derived from the plasma 
PF-06755347 concentration-time profiles as defined in Table 10 for each participant and 
treatment, as applicable, using noncompartmental analysis of concentration-time data.  
Samples below the lower limit of quantitation will be set to zero for analysis.  Actual sample 
collection times will be used for the pharmacokinetic analysis. 


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Table 10.
Plasma Pharmacokinetic Parameter Definition 
Parameter
Definition
Mode of Determination
Cmax
Maximum plasma concentration
Observed directly from data
Cmax (dn)
Dose normalized Cmax
Cmax/Dose
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence
AUClast
Area under the plasma concentration-time 
profile from time zero to the time of last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUClast(dn)
Dose normalized AUClast
AUClast/Dose
AUCinf a
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
AUCinf (dn)a
Dose normalized AUCinf
AUCinf/Dose
t½a
Terminal half-life
Loge(2)/kel,
where kel is the terminal phase rate constant 
calculated by a linear regression of the 
log-linear concentration-time curve.  Only 
those data points judged to describe the 
terminal log-linear decline will be used in 
the regression.
CL (IV)a
Systemic Clearance
Dose/AUCinf
Vss (IV)a
Volume of distribution at steady-state
CL*MRT where 
MRT=(AUMCinf/AUCinf )–(DOI/2)
CL/F (SC)
Apparent clearance
Dose/AUCinf for SC route
Vz/F (SC)
Apparent volume of distribution
Dose / (AUCinf *kel) for SC route
F (SC)
bioavailability
F = AUCinf,sc/ AUCinf,iv
a.
If data permit.
Abbreviation: AUMC = area under the first moment plasma concentration curve; dn=dose normalized to a 
1 mg dose; DOI = duration of infusion; MRT = mean residence time.
Actual PK sampling times will be used in derivation of PK parameters.
The supporting data from the estimation of t½ will also be reported:  the terminal phase rate 
constant (kel); the first, last, and number of time points used for the log-linear regression 
(kel,t(lo), kel,t(hi), and kel,t(n)); the goodness-of-fit statistic from the regression (r2); and the 
percent of the area under the plasma concentration-time curve from time zero to infinite time, 
AUCinf, obtained by forward extrapolation (AUCextrap%).


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9.5.1.1. Statistical Methods
No formal inferential statistics will be applied to the pharmacokinetic data.
The plasma concentration of PF-06755347 will be listed and summarized descriptively by 
nominal PK sampling time and treatment group.  Individual participant, mean and median 
profiles of the plasma concentration-time data will be plotted by treatment group using actual 
and nominal times, respectively.  Mean and median profiles will be presented on both linear 
and log scales. 
If data allows, PK parameters will be descriptively summarized and plotted by treatment 
group.
If data permits, dose normalized (to 1 mg) AUCinf, AUClast and Cmax will be plotted against 
dose (using a logarithmic scale), and will include individual participant values and the 
geometric means for each dose.  These plots will be used to help understand the relationship 
between the plasma PK parameters and dose.
9.6. Pharmacodynamic Analysis
Baseline and change from baseline in cytokines and complement components will be 
summarized descriptively and plotted by dose.  
 
  Further details will be documented in the SAP. 
9.7. Analysis of Other Endpoints
Immunogenicity (ADA) results will be listed (including titers) and summarized by treatment 
group and time points. Participant level immune response will also be summarized by 
treatment. Effect of positive ADA on safety, PD and PK will be assessed, if appropriate.
Pharmacogenomic data will be collected and retained for future analyses, but will not be 
analyzed, specifically, for this study.
9.8. Safety Analysis
Adverse events, ECGs, BP, pulse rate, pulse oximetry, continuous cardiac monitoring by 
telemetry, and safety laboratory data will be reviewed and summarized on an ongoing basis 
during the study to evaluate the safety of participants.  Any clinical laboratory, ECG, BP, 
pulse rate or oxygen saturation abnormalities of potential clinical concern will be described.  
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
Medical history and physical examination information, as applicable, collected during the 
course of the study will be considered source data and will not be required to be reported, 
unless otherwise noted.  However, any untoward findings identified on physical 
examinations conducted during the active collection period will be captured as an AE, if 
those findings meet the definition of an AE.  Data collected at Screening that is used for 
inclusion/exclusion criteria, such as laboratory data, ECGs and vital signs will be considered 
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source data, and will not be required to be reported, unless otherwise noted.  Demographic 
data collected at Screening will be reported.
9.8.1. Electrocardiogram Analysis
Absolute values and changes from baseline for the ECG parameters, heart rate, QT interval, 
QTcF interval, PR interval and QRS interval will be summarized by treatment and time.  
Baseline will be average of triplicate measurement at pre-dose on Day 1.
The number (%) of participants with maximum post dose QTcF values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Table 11.
Categories for Safety QTcF
Borderline (msec)
Prolonged (msec)
Absolute Value
≥450 - <480
≥480
Absolute Change
30-<60
≥60
In addition, the number of participants with corrected and uncorrected QT values ≥500 msec 
will be summarized.
If more than one 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 three individual ECG tracings has a QTc value
≥500 msec, but the mean of the triplicates is not ≥500 msec, the data from the participants
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 postdose QTc value and the average 
of the pre-dose triplicate values on Day 1.
In addition, an attempt will be made to explore and characterize the relationship between 
plasma concentration and QT interval length using a PK/PD modeling approach.  If a PK/PD 
relationship is found, the impact of participant factors (covariates) on the relationship will be 
examined.
9.9. Interim Analysis
No formal interim analysis will be conducted for this study. 
However, as this is a Sponsor-open study, the Sponsor will conduct unblinded reviews of the 
data during the course of the study for the purpose of safety assessment, facilitating 
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Unblinded results will be reviewed by a designated limited number of Sponsor colleagues 
within the study team and an independent consulting safety reviewer.  The Data Blinding 
Plan will delineate study team members who will be involved in these unblinded reviews as 
well as steps to be instituted ahead of initiation of any unblinded review to ensure study 
integrity is maintained.  
9.10. Data Monitoring Committee 
This study will not use an external data monitoring committee.  However, the dose escalation 
subteam will include an external, independent safety reviewer (refer to Section 9.9).


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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, 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 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. 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 will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participants personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participants legally 
authorized representative.
A participant who is rescreened is required to sign another ICD even if the rescreening 
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  Participants will be 
told that they are free to refuse to participate and may withdraw their consent at any time and 
for any reason during the storage period. 
 
Participants who decline to participate in this optional research will not provide 
this separate signature.
10.1.3. 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 participant personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.4. 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 SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-Sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-Sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-Sponsored interventional studies at the same time the US Basic Results document is 
posted to 
www.clinicaltrials.gov
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  Policy 
0070 applies to new marketing authorization applications submitted via the centralized 
procedure since 01 January 2015 and applications for line extensions and for new indications 
submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 


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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.
10.1.5. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data).  The investigator 
is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic form and are password protected to prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The Sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for a minimum of 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 


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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 participants medical records.  The investigator will promptly 
provide copies of the inspection findings to the Sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the Sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.6. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from 
source documents must be consistent with the source documents or the discrepancies must be 
explained.  The investigator may need to request previous medical records or transfer 
records, depending on the study.  Also, current medical records must be available.
Definition of what constitutes source data can be found in the data collection guidelines.
10.1.7. 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 Sponsors procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.


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Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.8. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the Sponsor
30 days before submission.  This allows the Sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The Sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
Sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by 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.
10.1.9. Sponsors Qualified Medical Personnel
The contact information for the Sponsors appropriately qualified medical personnel for the 
study is documented in the study contact list located in the clinical trial management system 
(CTMS) and study team on demand (SToD) system.  
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participants 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 


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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.  


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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 12.
Safety Laboratory Tests
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
MPV
WBC count
Total neutrophils 
(Abs)
Eosinophils 
(Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes 
(Abs)
BUN/Urea
Creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
Total CO2 
(Bicarbonate)
AST, ALT
Total Bilirubin
Alkaline 
phosphatase
Uric acid
Albumin
Total protein
CRP
Ferritin
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
Urine drug screenb
HIV, HepBsAg, HepBc Ab and HCVAb 
testsc
QuantiFERON-TB Gold testc
eGFR (CKD-EPI)
RFc
ANAd
Free T3c, free T4c, TSHc, TSAbc
Total IgAc, Total IgGc
Lipid Profilef (total cholesterol, LDL, 
HDL, TG, and ApoB100)
Coagulation
Pregnancy
Cytokinese
D-dimer
Fibrinogen
PT/INR
PTT
(hCG)g
FSHh
IL-6
TNF-
IFN
Complement (C3a, Bb, C5a)
a.
Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase.
b.
At Screening and Day -1. The minimum requirement for drug screening includes cocaine, 
tetrahydrocannabinol (THC), opiates/opioids, benzodiazepines, and amphetamines.
c.
At Screening only applicable to all cohorts.
d.
Applicable to healthy participant cohorts only.
e.
Ad hoc cytokines for local or central lab evaluation will be collected if CRS is suspected and 
coincides with a day pharmacodynamic samples are not collected per the SoA.  Local lab evaluation 
of cytokine is only required if the site require this information for safety management.
f.
Clinically significant dyslipidemia for all participants is to be determined by investigator judgment.
g.
Urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/EC. Serum or urine b-hCG tests are for female participants of childbearing potential at a local 
lab.
h.
For confirmation of postmenopausal status only.


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
Participants may undergo random urine drug testing at the discretion of the 
investigator.  Drug testing conducted prior to dosing must be negative for participants 
to receive IP.

Any remaining serum/plasma from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained 
and stored for the duration of the study. 
 
  These data will not be included in the CSR.  Samples to 
be used for this purpose will be shipped to either a Pfizer approved BBS facility or 
other designated laboratory and retained for up to 1 year following the completion of 
the study.
Investigators must document their review of each laboratory safety report.
CCI


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as 


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an AE/SAE unless it is an intentional overdose taken with possible suicidal/self 
harming intent.  Such overdoses should be reported regardless of sequelae.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent.  Such overdoses should be reported regardless of 
sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.


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10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect


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f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition.  These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.

Suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious.  The event may be suspected from clinical 
symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are 
considered synonymous.  These cases are considered unexpected and handled as 
serious expedited cases by pharmacovigilance personnel.  Such cases are also 
considered for reporting as product defects, if appropriate.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF 
and for reporting serious adverse events on the Clinical Trial (CT) SAE Report Form to 
Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the investigational product under study during 
pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None


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Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is 
not recorded.
All (and exposure during 
pregnancy [EDP] 
supplemental form for 
EDP)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participants 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities.  An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.

An event is defined as “serious” when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.


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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the Sponsor.  However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the Sponsor.

The investigator may change his/her opinion of causality in light of follow-up
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the Sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such 
an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 


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possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the Sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the 
electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data 
become available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.


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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements for the 
duration of the study through final study release of the participant (inclusive of final extended 
immune follow-up visit, if required), or through at least 28 days after the last dose of IP 
(whichever is longer).

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent. 
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

In addition to male condom use, a highly effective method of contraception must be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.1).
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3);
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), as described below, during the intervention period and for at 
least 28 days or 5 terminal half-lives (whichever duration is longer) after the last dose 
of study intervention, which corresponds to the time needed to eliminate any 
reproductive safety risk of the study intervention. If a highly effective method that is 
user dependent is chosen, a second effective method of contraception, as described in 
Section 10.4.4, must also be used. The investigator should evaluate the effectiveness 
of the contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.


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10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenarchal.
2. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (eg, mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participants medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in 
the participants medical record for the study.
3. Postmenopausal female.

A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 

A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.


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10.4.4. Contraception Methods
Implantable progestogen only hormone contraception associated with inhibition of 
ovulation.
Intrauterine device.
Intrauterine hormone-releasing system.
Bilateral tubal occlusion (eg, bilateral tubal ligation).
Vasectomized partner.

A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and 
the absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
Combined (estrogen  and progestogen containing) hormonal contraception associated 
with inhibition of ovulation.

Oral;

Intravaginal;

Transdermal.
Progestogen only hormone contraception associated with inhibition of ovulation.

Oral;

Injectable.
Sexual abstinence.

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent: 

Male or female condom with or without spermicide; 

Cervical cap, diaphragm, or sponge with spermicide; 


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
A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods).
Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an 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 partners pregnancy.
If a participant’s partner becomes or is found to be pregnant during the participants 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 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.


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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.

Genetic research may consist of the analysis of 1 or more candidate genes or the 
analysis of genetic markers throughout the genome or analysis of the entire genome
(as appropriate).

The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to study intervention or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.

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 banking (see Section 8.7.2 and 8.8.4) will be stored indefinitely or 
other period as per local requirements.  

Participants may withdraw their consent for the storage and/or use of their banked 
biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed.  Data already generated from the samples will 
be retained to protect the integrity of existing analyses.  

Banked biospecimens will be labeled with a code.  The key between the code and the 
participants personally identifying information (eg, name, address) will be held at the 
study site and will not be provided to the sample bank.


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 × ULN 
should be monitored more frequently to determine if they are an “adaptor” or are 
“susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede 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 
participants individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and Tbili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a Tbili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR Tbili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of Tbili above the normal range: Tbili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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Rises in AST/ALT and Tbili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the Sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and Tbili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), PT/INR, total bile acids, and alkaline 
phosphatase.  Consideration should also be given to drawing a separate tube of clotted blood 
and an anticoagulated tube of blood for further testing, as needed, for further 
contemporaneous analyses at the time of the recognized initial abnormalities to determine 
etiology.  A detailed history, including relevant information, such as review of ethanol, 
acetaminophen (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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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events 

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.

Newonset- atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration.

Frequent premature ventricular complexes (PVCs), triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events 

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented periods 
of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate 
<40 bpm), accelerated idioventricular rhythm (40< × <100), and 


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monomorphic/polymorphic ventricular tachycardia >100 bpm (such as torsades de 
pointes).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events

Change in pattern suggestive of new myocardial infarction. 

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all-inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: 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 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). 
10.8.1. Eligibility 
While SARS-CoV-2 testing is not mandated for this study, local clinical practice standards 
for testing should be followed. A participant should be excluded if they have a positive test 
result for SARS-CoV-2 infection, is known to have asymptomatic infection, or are suspected 
of having SARS-CoV-2. Participants with active infections are excluded from the study. 
When the infection resolves, the participant may be considered for re-screening. 
10.8.2. Telehealth Visits 
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the SoA or unscheduled 
visits. Telehealth visits may be used to continue to assess participant safety and collect data 
points. Telehealth includes the exchange of healthcare information and services via 
telecommunication technologies (eg, audio, video, video-conferencing software) remotely, 
allowing the participant and the investigator to communicate on aspects of clinical care, 
including medical advice, reminders, education, and safety monitoring. 
The following assessments must be performed during a telehealth visit: 

Review and record study intervention(s), including compliance and missed doses. 

Review and record any AEs and SAEs since the last contact.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 

Review and record contraceptive method and results of pregnancy test. Confirm that 
the participant is adhering to the contraception method(s) required in the protocol. 
Refer to Section 10.4. 
Study participants must be reminded to promptly notify site staff about any change in their 
health status.


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10.8.2.1. 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 as indicated in 
Section 10.2. 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. 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 IU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. 
10.8.2.2. 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. 
10.8.3. Adverse Events and Serious Adverse Events 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided. It is recommended that the investigator discuss 
temporary or permanent discontinuation of study intervention with the Sponsor before 
continuing treatment.


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10.9. Appendix 9: Grading System for Pro-Inflammatory-Related Adverse Events
Adverse 
Event 
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Vomiting
1 - 2 episodes 
(separated by 
5 minutes) in 
24 hrs
3 - 5 episodes 
(separated by 
5 minutes) in 
24 hrs
≥6 episodes 
(separated by 
5 minutes) in 
24 hrs; tube 
feeding, TPN or 
hospitalization 
indicated
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Diarrhea
Increase of 
<4 stools per day 
over baseline; 
mild increase in 
ostomy output 
compared to 
baseline
Increase of 4 - 6 
stools per day 
over baseline; 
moderate increase 
in ostomy output 
compared to 
baseline
Increase of 
≥7 stools per day 
over baseline; 
incontinence; 
hospitalization 
indicated; severe 
increase in ostomy 
output compared to 
baseline; limiting 
self-care ADL
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Abbreviations: ADL = activities of daily living; TPN = total parenteral nutrition.


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10.10. Appendix 10: CRS Grading System and Management 
CRS is a non-antigen-specific cytokine-associated toxicity that occurs as a result of 
high-level immune activation. Cytokine release with fever and headache have been reported 
to occur with IVIg infusion and meets current criteria for Grade 1 CRS; it may occur with 
PF-06755347 administration.11 Based upon the mechanism of action of PF-06755347, CRS, 
if it occurs, is expected to be manageable through awareness and supportive care. 
Early recognition and intervention should be undertaken at the first signs or symptoms of 
CRS; signs may include pyrexia, shivering/rigors, tachycardia, tachypnea and/or hypotension 
and symptoms may include headache, nausea, chills, vomiting, and back ache when 
temporally related to PF-06755347 administration in the absence of alternative etiologies.  
Grading by the more recent ASTCT CRS criteria12 (Table 13) will be captured on the CRS 
CRF.  
Table 13.
ASTCT CRS Revised Grading System12
CRS parameter:
Fever*
With Hypotension
And/or† Hypoxia
Grade 1
Temp. ≥38°C
None
None
Grade 2
Temp. ≥38°C
Not requiring vasopressors
Requiring low-flow‡ nasal 
cannula, low-flow‡ facemask or 
blow-by
Grade 3
Temp. ≥38°C
Requiring a vasopressor with or 
without vasopressin
Requiring high-flow‡ nasal 
cannula, high-flow‡ facemask, 
nonrebreather mask, or Venturi 
mask
Grade 4
Temp. ≥38°C
Requiring multiple vasopressors 
(excluding vasopressin)
Requiring positive pressure 
(eg, CPAP, BiPAP, intubation 
and mechanical ventilation)
Organ toxicities associated with CRS should still be graded according to CTCAE v4.03 and do not 
influence CRS grading.
* Fever is defined as temperature ≥38°C and not attributable to any other cause.  In patients who have CRS 
then receive antipyretic therapy, fever is no longer required to grade subsequent CRS severity.  In this 
case, CRS grading is driven by hypotension and/or hypoxia.
† CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other 
cause.  For example, a patient with temperature of 39.5°C hypotension requiring 1 vasopressor, and 
hypoxia requiring low-flow nasal cannula is classified as grade 3 CRS.
‡ Low-flow nasal cannula or facemask is defined as oxygen delivered at ≤6 L/min. Low flow also includes 
blow-by oxygen delivery, sometimes used in pediatrics.  High-flow nasal cannula or facemask is defined 
as oxygen delivered at >6 L/min.  This is modified from original ASTCT criteria to differentiate between 
low-flow and high-flow facemask.
Abbreviations: ASTCT = American Society for Transplantation and Cellular Therapy; BiPAP = bilevel positive airway 
pressure; CPAP = continuous positive airway pressure; CRS = cytokine release syndrome; CTCAE = Common 
Terminology Criteria for Adverse Events.


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CRS identification and management (adapted from Neelapu et al13)

Monitor vital signs (temperature, blood pressure, pulse and SpO2) according to SoA
and at a minimum, every 1 hour until vital signs have returned to baseline levels.  If 
clinical symptoms suggestive of CRS are reported by the participant outside of the 
scheduled windows of the SoA, close monitoring of vital signs should be conducted 
as above.
Fever (body temperature ≥38.0°C)

Acetaminophen/paracetamol and cooling blanket for the treatment of fever.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen/naproxen can be 
used as second treatment option for fever if not contraindicated.

Assess for infection using blood and urine cultures and nasal swab for COVID-19 as 
indicated.

Initiate oral or IV fluids for hydration as tolerated. Increase fluid rate from the 
existing IV catheter.
Hypotension (Systolic Blood Pressure <90 mmHg or a decrease of 20% from baseline levels 
in either systolic or diastolic blood pressure whichever is lower).

IV fluid 500 ml of normal saline given as rapidly as the existing safety IV cannula 
can tolerate.

May give a second 500 ml of normal saline if participant remains hypotensive or 
participant’s symptoms of hypotension do not resolve.
Corticosteroid Use:

Up to a total of hydrocortisone 200 mg or dexamethasone 10 mg or 
methylprednisolone 125 mg IV. should be used  if IV fluid does not stabilize blood 
pressure.  At the investigator’s discretion, this dose may be split in half, with the first 
half given during the first Normal Saline infusion and the second half given if 
symptoms and signs do not improve within one hour. If participant remains 
hypotensive after full dose of corticosteroids and fluid is administered or is otherwise 
not responding to therapy, or at investigator’s discretion, initiate transfer to ICU for
consideration of vasopressors or optional anti-IL-6 agents (tocilizumab 8 mg/kg 
(maximum dose 800 mg) IV or siltuximab 11 mg/kg IV).
Hypoxia

If SpO2 <94%, initiate supplemental oxygen via nasal cannula or low flow mask, and 
increase flow to maintain SpO2 to ≥94%.

Initiate transfer to ICU at investigator’s discretion, or if oxygen flow rate exceeds 
6 L/min or mask with  fraction of inspired oxygen (FiO2) >40%.


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10.11. Appendix 11: CTCAE (version 4.03) Grading System for Infusion-Related 
Reactions
Adverse 
Event 
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Infusion 
related 
reaction
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment 
(eg, antihistamines, 
NSAIDS, narcotics, IV 
fluids); aprophylactic 
medications indicated 
for ≤24 hrs
Prolonged (eg, not 
rapidly responsive to 
symptomatic 
medication and/or 
brief interruption of 
infusion); recurrence 
of symptoms 
following initial 
improvement; 
hospitalization 
indicated for clinical 
sequelae
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
a. Investigator may pause the infusion if needed in the case of an infusion related reaction, and apply 
prophylactic treatment after the event has resolved, order to mitigate against additional infusion related 
symptoms if/once the infusion was restarted. 
Abbreviations: NSAID = non-steroidal anti-inflammatory drug; IV = intravenous.


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10.12. Appendix 12: Country Specific Requirements
10.12.1. Czech Republic 
Schedule of Activities Error! Not a valid bookmark self-reference.
Table 14.
Schedule of Activities for SC Cohorts of ITP Participants- Czech Republic ONLY
Protocol Activity
Screen
Clinical Confinement
Outpatient Follow-up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
7
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5 
6
8
12
24 36 48 72
96 120
168 240 336 504
672
840
Informed consent
X
Demography (including Height)
X
Outpatient Visit
X
X
X
X
X
X
X
X
Study Site Confinement
X














X
Randomization
X
Discharge
X
Chest X-rayb
X
QuantiFERON-TB Gold test
X
HIV, HepBsAg, HepBcAb, 
HCVAb tests
X
Test for rheumatoid factor, 
anti-nuclear antibody, Total IgG 
and Total IgA, TSH, thyroxine 
(free T4), and triiodothyronine
(free T3) TSAb; Lipid profile.  
X
Inclusion/Exclusion
X
X
Medical history; history of illegal 
drug, alcohol & tobacco use
X
Xc
Medication history
X
Xc
Weight
X
X
X
X
Urine drug screening
X
X
FSHh
X
Serum Pregnancyi
X
X
Review contraception use
X
X
X
X
X
X
X
X
X
X
Physical examinationd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Protocol Activity
Screen
Clinical Confinement
Outpatient Follow-up Visits
Study Day/Visit Window (days)
-56 to 
-2
-1a
1
2
3
4
5
6
7
8
11
±2
15
±2
22
±2
29
±2
36
±3
50
±3
71
±3 or ET
Hour(s) Post Dose 
0
pre-
dose
0.5
1
3
3.5
4
5 
6
8
12
24 36 48 72
96 120
168 240 336 504
672
840
Hematology & Coagulation (PT, 
INR, PTT, D-dimer & fibrinogen) 
Safety Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry/Urinalysis/Other Safety 
Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECGe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP, pulse rate, 
temperature)f
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
Pulse Oximetry
X
X
X
X
X
X
X
X
X
X
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
ADA blood sampling
X
X
X
X
X
X
 
 
 
SC Administration
X
SC Injection site assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testj
X
X
X
Serious and non-serious Adverse 
Event monitoring
X
X



















X
Prior/Concomitant treatments
X
X
X
X









X
a.
Admission may be on Day -2 or Day -1 at the discretion of the Investigator.  If a participant discontinues early they should, when possible, return to complete assessments 
outlined at Day 36.  The follow-up period may be extended if any participant in a particular cohort is tested positive for anti-drug antibody to PF-06755347 or has detectable 
concentration of PF-06755347 at final study visit.  If there is an ET, the Day 36 schedule will be followed.
b.
Chest X-ray results within 3 months of screening visit otherwise a chest X-ray must be performed at screening and results obtained prior to admission. 
c.
Update medication history, alcohol and tobacco use since screening. 
d.
Full PE may be done at screening or may be deferred to admission at the discretion of the investigator.  If a full PE is performed at screening, a brief PE may be performed at 
admission.  Limited PE may be performed at discharge or at any outpatient visit at the discretion of the investigator. Additional PE to be performed in Czech Republic at 
investigator’s discretion. Post dose day 1 PE to be performed at a consistent time for each of their participants. 
CCI


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e.
Single ECG at screening and scheduled outpatient visits; triplicate ECG at all other time points (including unscheduled, early termination, or extended immune follow up 
visit). 
f.
Vital signs measurement (including BP, pulse rate & temperature) triplicate at pre dose only, at the discretion of the investigator triplicate assessments may be taken at other 
timepoints.  Either oral or tympanic method for temperature determination is allowed; however the method should be used consistently for each participant.
g.
Banked biospecimen may be collected on admission or Day 1 (prior to dosing).  If not collected on the designated collection day, collect at the next available time point when 
biospecimens are being collected in conjunction with a participant visit.
h.
Serum FSH will be performed to confirm postmenopausal status for females (at the investigator’s discretion whether to confirm post-menopausal status by FSH if greater than 
5 years since last menses.
i.
Serum pregnancy test will be conducted at a local lab. For female participants of childbearing potential, 2 negative pregnancy tests are required prior to dose on Day 1 
(1 negative serum pregnancy test at Screening and 1 negative urine pregnancy test on Day 1). Results of serum pregnancy test from Day -1 are not required prior to dosing.
j.
Urine pregnancy test will be conducted locally in females of ITP cohorts.


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Section 5.4 Exclusion Criteria for Participants with ITP
Exclusion number 15.) History of thromboembolic events:
Participants who in the opinion of the investigator, based upon medical history, have 
predisposing factors other than ITP for the development of thromboembolic disease
(eg, Factor V Leiden mutation, long-term use of hormonal contraception, history of 
thromboembolic events, antiphospholipid antibody), are prohibited from entering the study.
Section 6.5.1 Rescue Medication:
For any event of bleeding associated with ITP it is expected that rescue therapies be 
administered to the participant according to the local standard procedures of the centre in 
accordance with the recommended procedures of the Czech Society of Haematology.
Given this is a single time administration, if a participant requires rescue therapy for any 
event, then they remain eligible to continue participation in the study in order to document
adequate assessment of the safety profile.
Section 6.7 Dose Escalation:
Administration of PF-06755347 to female participants in the Czech Republic will be deferred 
until the safety data used for dose escalation decisions from at least 6 female participants 
(from other participating countries) has been reviewed by the Sponsor’s members of the dose 
escalation subteam according to the criteria outlined in Section 6.7 of the protocol and found 
to be consistent with healthy male participant data.
The dose escalation subteam will perform a review of safety, PK, cytokine, and complement 
data of the first 6 female participants with ITP who receive study drug to assess immunologic 
response similarity to males. 
Section 10.4.3. Women of Childbearing Potential 
The definition of postmenopausal women will be in accordance with point 1.1 of the CTFG 
Recommendations.
For the purpose of this document, a woman is considered of childbearing potential 
(WOCBP), ie, fertile, following menarche and until becoming post-menopausal 
unless permanently sterile. Permanent sterilisation methods include hysterectomy, 
bilateral salpingectomy and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women 
not using hormonal contraception or hormonal replacement therapy. However in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.


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10.13. Appendix 13 Protocol Amendment History
Amendment 7
16 December 2021
1. Section 2.1 Study Rationale
Change: added context 
Rationale: explain the rationale for the inclusion 
of participants with ITP
2. Section 4.1 Overall Design
Change: specified timing for the initiation of 
ITP cohorts
Rationale: clarify dosing details 
3. Section 4.2.1.3.3 Subcutaneous Administration 
in Participants with ITP
Change: added demonstration of pharmacologic 
activity at doses for ITP cohorts
Rationale: justify dose selection
4. Sections 6.6. and 6.7 Dose Progression and 
Escalation rules
Change: added information unique to ITP 
cohorts
Rationale: clarify rules
5. Section 10.4.4 Contraception Methods
Change: added second effective contraception 
methods
Rationale: to be consistent with CTFG guidance 
Amendment 6
27 October 2021
1. Updated appropriate sections throughout the 
protocol to include cohorts of participants with 
ITP.
Rationale: to obtain safety, tolerability, and PK 
data in participants with chronic and persistent 
ITP. 


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2. Added Randomization at Day 1 to SoA Tables 2 
& 3. 
Rationale: to clarify timing.
3. Updated the SoA for HP SC Table 2 with the 
following: 

Anti- cardiolipin antibody: removed 
screening assessment.
Rationale: Single values for anti-cardiolipin 
antibodies are uninformative for mitigation of 
thromboembolic risk associated with Ig products 
and by extension PF-06755347.

Cytokine and complement biomarkers: 
Added 96-hour (Day 5) and removed 1, 3 & 
8 hour collections.

PK blood sampling: Added 96-hour (Day 5) 
collection.
Rationale: Sample timepoints capture observed 
Tmax and Cmax of SC administration.

Telemetry: footnote added to indicate only
participants dosed prior to acceptance to 
amendment 6 will have telemetry 
performed.
Rationale: IV administration with significantly 
higher concentrations demonstrated no safety 
concern.

Chemistry, Urinalysis, Hematology and 
Coagulation Labs: Removed hour 6 
collection.
Rationale: Minimize unnecessary blood draws 
while maintaining safety for both populations; 
and is uninformative for SC cohorts.
4. Extended the dose progression safety 
monitoring data acquisition time from 72 to 
96 hours post dose for SC administration. 


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Rationale: Sample timepoints capture observed 
Tmax and Cmax of SC administration.
5. Added a separate SoA Table 3 for SC in 
participants with ITP. This includes serum and 
urine pregnancy, FSH, and Randomization on 
Day 1, and to remove screening autoantibodies, 
including anti-cardiolipin antibody.  
Rationale: female participants are included in 
the ITP cohorts thus requiring pregnancy 
testing; autoimmune disease will be assessed by 
the judgment of the PI in that active disease will 
be exclusionary. Exclusion will not be based on 
an autoantibody lab value.
6. Removed language in Section 1.1 Overall 
Design that described the implementation of 
additional safety monitoring that was 
incorporated into Amendment 5. 
Rationale: to delete redundancy.
7. Simplified the language of study participants in 
the Synopsis and Section 3.
Rationale: to improve readability.
8. Updated 4.2.1.3 Clinical Dose Selection to 
separate into HP IV, HP SC and ITP SC 
subsections. Deleted “to allow for dose 
escalation” in 4.2.1.3.3.
Rationale: easier to read; and allow for testing 
the most appropriate doses in participants with 
ITP. 
9. Updated 5.2 Exclusion Criterion #6 in HP SC to 
exclude only clinically significant dyslipidemia 
in the opinion of the investigator, and removed 
Exclusion Criterion # 11 for a positive 
anti cardiolipin antibody.
Rationale: Aligned identified risk factors for Ig 
products and by extension PF-06755347. 
Clinically significant dyslipidemia is a known 
risk factor for thromboembolic events. Single 


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values for anti-cardiolipin antibodies are 
uninformative for mitigation of thromboembolic 
risk in study population.
10. Updated 5.5.2 to allow participants with ITP to 
have caffeine and tobacco, and to allow all sites 
to screen for alcohol in breath, blood and/or 
urine. 
Rationale: to not add additional recruitment 
difficulty; avoids aerosol testing during 
COVID-19 pandemic.
11. Added female contraception text in 
Section 10.4.2 Female Participant Reproductive 
Inclusion Criteria and pregnancy testing text in 
Section 8.2.6 Pregnancy Testing.
Rationale: these requirements are necessary now 
with the inclusion of females in the ITP cohorts;
to ensure consistency with Clinical Trial 
Facilitation Group document with the definition 
of highly effective contraception methods.
12. Updated to Section 6.6 Dose Progression Pause 
Criteria.  
Rationale: added specific guidance for 
participants with ITP.
13. Updated footnotes within 10.2 Appendix 2 
Clinical Laboratory Tests Table 12 and removed 
anti-cardiolipin antibody.
Rationale: to make a clear distinction which 
screening labs apply to specific cohorts.
14. Added of Appendix 8 Section 10.8 Alternative 
Measures During Public Emergency. 
Rationale: to accommodate ongoing global 
pandemic.
15. Updated the term ‘participant’ throughout the 
protocol.


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Rationale: consistent use of terms. 
Amendment 5 
15 March 2021
1. Section 1.1 Overall Design: updated to include 
specific doses for subcutaneous (SC) 
cohorts 7-12.
Rationale: to provide clarity on subcutaneous 
dosing strategy.
2. Section 1.2 Schema: all cohorts including the 
optional Japanese are to dose in a sequential 
manner.
Table 3: updated to move the optional Japanese 
cohort to the SC group.
Rationale: implementation of sequential dosing for 
all cohorts including the optional Japanese will 
enhance safety monitoring.
3. Section 2.1 Study Rationale: updated to note 
that a maximum tolerated dose with IV has been 
achieved with Grades 1 and 2 CRS observed at 
doses of 0.7 and 1 mg/kg therefore no further IV 
dosing will occur.  Going forward, evaluation of 
the safety, tolerability and PK of PF-06755347 
will be conducted via the SC administration 
route. 
Rationale: The proposal is to re-start the study as 
described in this amendment with SC dosing.  
4. Section 4.1 Overall Design: updated total 
number of participants and specification of dose 
levels for SC cohorts
Rationale: to summarize the approximate total 
number of participants in IV and SC cohorts and to 
specify planned dose levels for SC administration.
5. Section 4.2 Dose Justification: updated Table 5 
with observed human exposure, added Table 6 
to provide drug exposure projections for SC 
dosing and included language in the Clinical 
Dose Selection Section 4.2.1.3.


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Rationale: to provide predicted exposures for 
planned SC dose levels.
6. Section 5.2 Exclusion Criteria: added language 
to #17 that an approved COVID-19 vaccine is 
considered a concomitant medication. Language 
has been added that participants that have 
received an approved vaccine should allow 28 
days prior to dosing with PF-06755347.
Rationale: to provide clarity on vaccine 
administration during the pandemic. 
7. Section 6.5.1 Rescue Medication: updated to 
include language regarding the availability of  
specific medications and an ICU.
Rationale: added per regulatory feedback.
8. Section 6.6 Dose Progression: stop criteria was 
updated.
Rationale: The previous protocol amendment stated 
in Section 6.6 Dose Progression included stopping 
criteria where the study would be stopped.  The 
clinical findings to date with the IV route illustrate 
an understanding of the time course of adverse 
events, CRS and laboratory abnormalities.  As a 
result, the proposal is to restart the study with SC 
administration because it is anticipated that the 
severity of CRS is potentially related to Cmax. 
Therefore, the SC route is predicted to decrease the 
Cmax by about 4-fold; thus reducing the risk to 
participants and the need to stop the study.
9. Section 10.8 Appendix 8 removed hypoxia and 
hypotension from the Grading System of 
Pro-Inflammatory-Related Adverse Events 
table.
Rationale: to minimize confusion as    these events 
are part of the CRS grading table in Section 10.9 
Appendix 9.
10. Section 10.9 Appendix 9: CRS Grading System 
and Management Guidelines: updated to be 


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more specific for the management of CRS and 
use of medication.
Rationale: to provide clarification and clearer 
expectations.
11. PACL dated 29 Sept 2020: clarifications were 
implemented into Section 1.2 Study Schematic 
to include a footnote referring to Section 4.2 
stating that actual dose levels are subject to 
change.
Rationale: to be consistent with language stated in 
Section 4.2 and 4.3.1.3 regarding dose adjustment.
Amendment 4
24 July 2020
1. Section 2.3 Benefit/Risk Assessment updated to 
include language during COVID-19 pandemic.
Rationale: Added information relevant to
benefit/risk assessment of this compound including 
the drug mechanism of action, long half-life, 
duration of in-house observation and follow-up 
requirements during the COVID-19 pandemic.
2. Section 5.2 Exclusion Criteria #21 condom and 
highly effective method of contraception are 
required.
Rationale: to ensure consistency with Clinical Trial 
Facilitation Group document with the definition of 
highly effective contraception methods.
3. Section 6.7 Dose Escalation deletion of bullet 3 
due to redundancy in Section 6.6.
Rationale: clarification of protocol language to 
make clear that a single serious adverse reaction 
will result in termination of escalation.
4. Section 6.8 Infusion or Injection Site Reaction 
Grade 3 serious changed to ‘life-threatening’.
Rationale: to clarify the distinction between 
intensity and seriousness of adverse events.
5. Section 7 Potential Cases of Acute Kidney 
Injury updated to include follow up 


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management language, Section 7.1 changed 
discontinuation visit to ‘early termination’ visit 
per SoA.
Rationale: clarified that continued follow-up within 
the protocol instead of the current language 
requiring withdrawal from the study.
6. Appendix 9 Section 10.9 CRS Grading and 
Management Guidelines updated to include 
detailed management guidelines, improved
context introduction and deletion of reference to 
management ‘at investigator’s discretion’.
Rationale: provided guidance on the management of 
cytokine release syndrome.
7. Appendix 4 Section 10.4.4 Contraception 
Methods removed methods  #9-12.
Rationale: consistency with Clinical Trial 
Facilitation Group document for clarification of 
effective methods of contraception.
Amendment 3
30 June 2020
1. Schedule of Activities (SoA) was updated to 
include:
a.
additional hours post dose timepoints (3.5, 4 & 
6) for assessing Vital signs, Pulse oximetry and 
PK; and additional 8 &12 hour post dose 
timepoints for cytokines and complement.
Rationale: to enhance participant safety monitoring, 
and aligning with the cytokine complement 
biomarker timepoints.
b. the addition of ‘discharge from site’ at Day 8.
Rationale: to provide clarity.
c.
separation of Safety Labs into two separate 
activities: Hematology/Coagulation Safety and 
Chemistry/Urinalysis/Other Safety Labs. 
Removal of Chemistry labs at post dose time 
points 1 & 3 hours.


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Rationale: Additional hematology/coagulation labs 
have additional collection times to monitor safety 
compared with chemistry labs and thus they were 
separated in the protocol.
d. addition of Day 11 outpatient visit.
Rationale: Correction of Inadvertent omission
e.
addition of Hematology/Coagulation Safety lab 
assessments post dose timepoints (1, 3, 5, 8, 12 
& 240 hours).
Rationale: increase safety surveillance.
f.
update to body temperature determination by 
allowing both oral and tympanic methods.
Rationale: acceptable as long as consistent.
g. addition of subcutaneous (SC) to the site 
assessment and PK blood sampling, and 
removed footnote regarding infusion site 
reactions (ISR), added a footnote regarding 
cytokine release syndrome (CRS) assessment 
and 1h safety and PK required only for infusion 
durations <2 hours.
Rationale: properly reflects cohort update and 
expectations.
2. Section 2 Introduction updated to include both 
ITP and CIDP indications consistent with 
clinical development plan.
3. Section 3 Objectives and Endpoints updated to 
include three subcutaneous cohorts.
Rationale: to explore PK/PD in SC route of 
administration for future clinical development.
4. Section 2.1 Drug Development Rationale was 
updated
Rationale: to align with recently updated April 2020 
IB.


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5. Section 1.2 Study Schema was updated to a two-
fold increment of ascending doses at cohort 6 
instead of cohort 8; also includes the addition of 
up to three subcutaneous cohorts.
Rationale: to increase participant safety due to 
emerging safety data on cytokine release and to 
determine PK following SC administration.
6. Section 4.3 Table 3 Predicted Exposure was 
updated.
Rationale: Based on emerging safety, dosing 
increments were amended and thus predicted 
exposure reflects the updated dose levels.  
7. Section 5.2 Exclusion Criteria #3 (positive ADA 
antibody result) was removed.
Rationale: The recommendations by health 
authority in 2017 were misinterpreted by the 
Sponsor and upon further review of the FAMHP 
meeting minutes it became clear that pre-existing 
ADA was not a suggested exclusion criterion for the 
study.
Rationale: to add safety precaution and ensure 
specific exclusion criterion.
8. Section 6.1 added guidelines on SC injections.
Rationale: required with the addition of SC cohorts.
9. Section 6.3 Randomization and Blinding 
updated to include IRT system.
Rationale: required with the addition of external 
sites.
10. Section 6.4 Study Intervention compliance The 
content of one Protocol Administrative 
Clarification Letter (PACL) 24Feb2020 was 
added to define medication error.
Rationale: to provide clarity.


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11. Section 6.5.1 Cytokine Release Syndrome and 
Section 6.8 Infusion or Injection Site Reaction 
details were added.
Rationale: required per associated risk with the IP.
12. Section 6.6 Dose Progression added language 
that any mitigation plan may need to be 
discussed with the Institutional Review Board 
(IRB) or Regulatory Authority as appropriate; 
removed grade 1 fever, pause criteria were 
clarified.
Rationale: Cytokine release syndrome (CRS) 
guidelines have been updated in the protocol and 
reflect that a Grade 1 fever alone is indicative of a 
Grade 1 toxicity for CRS. Language added to make 
decision tree clearer. Dose Progression section has 
been updated to reflect the updated guidelines.
13. Section 6.7 Dose Escalation included the 
maximum exposure observed in individual 
participants within a cohort rather than the mean 
exposure should be taken into account for dose 
escalation, moving this language from 
Section 6.6.
Rationale: Per HMR UK site request, the PK rule 
for stopping escalation has been updated per site 
request.
14. Section 8.10.4 Banked Biospecimens for 
Biomarkers was updated.
Rationale: the protocol was updated to be consistent 
with template.
15. Section 8.11 Blood Volume Table updated to 
reflect increased safety lab surveillance and SC 
cohorts.
Rationale: to accurately reflect changes made to 
protocol
16. Section 9.5.1 Derivation of PK parameters 
Table 6 was updated with definitions.


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Rationale: SC dosing will be explored and therefore 
different PK parameters will be assessed.
17. Section 10.2 Appendix 2 Clinical Laboratory 
Tests Table 8 was updated with a separate 
Coagulation and Cytokine/complement section.
Rationale: to clarify the specific tests required for 
the Coagulation panel and the 
Cytokine/complement panel labs.
18. Section 10.9 Appendix 9 added Cytokine 
Release Syndrome Mitigation and Table 9 
ASTCT CRS revised grading system.
Rationale: required per identified IP risk.
19. Additionally typographical errors were 
corrected.
20. Section 6.6 Deleted “Two participants or more 
develop similar clinically significant laboratory, 
electrocardiogram (ECG), or vital sign 
abnormalities, in the same organ class, 
indicating dose-limiting intolerance”.
Rationale: this text is deleted from Section 6.6 and 
moved to section 6.7; where it is applicable to the 
entire cohort: “If 50% or more of the participants 
receiving active drug at a given dose level (but not 
participants receiving placebo) develop similar 
clinically significant laboratory, ECG, or vital sign 
abnormalities, in the same organ class, indicating 
dose-limiting intolerance”.
Amendment 2
10 October 2019
Schedule of Activities, Section 8. Study 
Assessments and Procedures and Section 8.1. 
Screening. To enable continuous screening and to 
assist with participant scheduling for all planned 
cohorts the overall screening window has been 
increased for 28 days to 56 days.
Reference to the Pfizer Clinical Research Unit 
(CRU) has been removed throughout the protocol 
and where appropriate the text refers simply to 


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“site”, so as to allow this protocol to be used at 
multiple centres, if required. 
Section 4.2 Scientific Rationale for Study Design, 
Section 5.1 Inclusion Criteria # 1. The age range for 
this study has been changed from 18-40 to 18-55. 
The overall risk benefit profile remains unchanged. 
Section 5.1 Inclusion criteria:

Inclusion criteria # 5: The body weight 
criteria has been modified to >50 kg so as to 
broaden the pool of participants that are 
eligible for enrolment.  However, the overall 
infusion volume based on weight must not 
exceed 1L. 

Inclusion Criteria # 21. The AST/ALT 
criteria  has been amended to AST or ALT 
level >1.25 × upper limit of normal (ULN) 
which more adequately reflects the 
variability of AST/ALT seen in healthy 
participants whilst maintaining a suitable 
threshold to exclude participants with 
potential pre-existing liver issues.

Section 5.2 Exclusion Criteria:

Exclusion # 1. Duplicate language around 
drug allergies has been removed. 
Section 6.1.1. Administration. To allow greater 
flexibility in scheduling the administration window 
has been increase for 08:00 (plus or minus 2 hours) 
to 08:00 (plus or minus 3 hours). 
Section 8.4.6. Continuous Cardiac Monitoring by 
Telemetry. As admission may occur as early as 
Day-2, the language has been updated to allow 
earlier measurements of cardiac function replacing 
“in the 24 hours prior to dosing” with “between 
admission and dosing”. 
Amendment 1
03 October 2018
The primary reason for Amendment 1 is to revise 
the Dose range and the Dose Escalation criteria to 


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address FAMHP guidance. Sections revised 
include:
General updates: New global protocol template 
used.
Section 2.23: Non clinical safety: Updated with low 
dose non-human primate data
Section 3: Objectives and Endpoints: Fluorescence-
activated cell sorter (FACS) analysis of immune cell 
subsets, RNA biomarkers, phagocytosis and 
complement-dependent cytotoxicity (CDC) 
biomarkers removed.
Section 4: Study Design. Updated to include two 
lower dose cohorts of 0.01 mg/kg and 0.03 mg/kg. 
The 45 mg/kg dose cohort has been removed.
Section 4.3.1.3: Clinical dose. Updated the safety 
margins based on the non-human primate data 
removing reference to the rat data. 
Section 5: Female participants removed with all 
associated text. Study will be conducted in male 
participants only.
Table 6: Intravenous infusion guidance updated to 
include the two lower dose cohorts of 0.01 mg/kg 
and 0.03 mg/kg.
Section 6.6 and 6.7: Dose progression and Dose 
Escalation: Updated to reflect the use of a 
sequential dosing scheme. 
Original 
protocol
14 June 2017
N/A


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10.14. Appendix 14: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
Abs
absolute
ADA
anti-drug antibody
ADL
activities of daily living
AESI
adverse event of special interest
ALT
alanine aminotransferase
ApoB100
apolipoprotein B100
ANOVA
analysis of variance
AST
aspartate aminotransferase
ASTCT
American Society for Transplantation and Cellular Therapy
AUC
area under the curve
AUC168
area under the concentration-time curve from time 0 to 168 hours
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
AUMC
area under the first moment plasma concentration curve
Bb
activated factor B
BBS
Biospecimen Banking System
BiPAP
bilevel positive airway pressure
BMI
body mass index
BP
blood pressure
BPM
beats per minute
BRC
Benefit Risk Committee
BUN
blood urea nitrogen
C1q
Complement component 1q
C3a
Complement 3a
C5a
Complement 5a
Cav
average concentration
CA
Competent Authority
CDC
complement-dependent cytotoxicity
CDS
core data sheet
Ceff
efficacious concentration
CFR
Code of Federal Regulations
CHO
Chinese Hamster Ovary
CI
confidence interval
CIA
Collagen-Induced Arthritis
CIDP
chronic inflammatory demyelinating polyneuropathy
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CL
clearance
CL/F
apparent clearance
Cmax
peak or maximum observed concentration
CO2
carbon dioxide (bicarbonate)
COVID-19
Corona virus disease 2019
CPAP
continuous positive airway pressure
CRF
case report form
CRO
contract research organization
CRS
cytokine release syndrome


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Abbreviation
Term
CSA
clinical study agreement
CSF
cerebrospinal fluid
CSR
clinical study report
CT
Clinical Trial
CTA
clinical trial application
CTC
Common Terminology Criteria
CTCAE
Common Terminology Criteria for Adverse Events
CTFG
Clinical Trials Facilitation and co-ordination Group
CTMS
Clinical Trial Management System
CV
cardiovascular
DAI
Dosing Administration Instructions
DCT
data collection tool
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DOI
duration of infusion
EAN
experimental autoimmune neuritis
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic CRF
EDCMS
electronic data capture and management system
EDMC
external data monitoring committee 
EDP
exposure during pregnancy
EDR
Extemporaneous Dispensing Record
EDTA
edetic acid (ethylenediaminetetraacetic acid)
eGFR
estimated glomerular filtration rate
EIU
exposure in utero
EMA
European Medicines Agency
EOI
end of infusion
ERB
external review board
ET
Early termination
EU
European Union
EudraCT
European Clinical Trials Database
FcRs
Fcreceptors
FDA
Food and Drug Administration (United States)
FDAAA
Food and Drug Administration Amendments Act (United States)
FFPE
formalin-fixed paraffin-embedded 
FIH
first-in-human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLP
Good Laboratory Practices
hCG
human chorionic gonadotropin
HDL
high density lipoprotein
HDL-C
high density lipoprotein cholesterol
HCVAb
hepatitis C antibody
HepBsAg
hepatitis B surface antigen
HepBcAb
hepatitis B core antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HP
Healthy participant
HR
heart rate


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Abbreviation
Term
Hr
hour
HRT
hormone replacement therapy
HSV-1
Herpes Simplex Virus 1
HSV-2
Herpes Simplex Virus 2
IB
investigators brochure
iC3b
inactive product of complement component 3b
ICD
Informed consent document
ICE
IGIV-C CIDP efficacy
ICH
International Conference on Harmonisation
ID
Identification
IEC
independent ethics committee
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgG2
Immunoglobulin G2
IND
investigational new drug application
INR
international normalized ratio
IFN
Interferon gamma
IL-1RA
Interleukin-1 receptor antagonist
IL-6
Interleukin-6
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
ISR
infusion site reaction
ITP
idiopathic thrombocytopenic purpura or immune thrombocytopenia
IUD
intrauterine device
IUS
Intrauterine system
IV
intravenous
IVIg
intravenous immunoglobulin
IWR
interactive Web-based response
K2EDTA
dipotassium ethylene diamine tetraacetic acid
LDL
low density lipoprotein
LDL-C
low density lipoprotein-cholesterol
LFT
liver function test
LOEL
lowest observed effect level
LPD
local product document
MCH
Mean corpuscular hemoglobin
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
MHRA
Medicines and Healthcare products Regulatory Agency
mDC
myeloid dendritic cells
MedDRA
medical Dictionary for Regulatory Activities
MRT
mean residence time
MTD
maximum tolerated dose
N/A
not applicable
ND
Not done
NHP
non-human primate
NK
natural killer
NOAEL
no observed adverse effect level
NOEL
no observed effect level
NSAID
non-steroidal anti-inflammatory drug
PACL
protocol administration clarification letter


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Abbreviation
Term
PCV
premature ventricular complexes
PD
Pharmacodynamics
PE
physical examination
PEOI
prior to end of infusion
PG 
Pharmacogenomics
PI
principal investigator
PK
Pharmacokinetics
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QTc
corrected QT
QW
weekly
RBC
red blood cell
RMC
Risk Management Committee
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous
SC Ig
Subcutaneous immunoglobulin
SCr
serum creatinine
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SoA
Schedule of Activities
SOP
standard operating procedure
SPC
summary of product characteristics
SRSD
single reference safety document
SToD
Study team on demand
SUSAR
suspected unexpected serious adverse reactions
t½
terminal half-life
T3
triiodothyronine
T4
thyroxine
TB
tuberculosis
Tbili
total bilirubin
TCC
total cell count
TG
triglycerides
Tmax
time to reach maximum concentration
TNF-
Tumor necrosis factor alpha 
THC
tetrahydrocannabinol
TPN
Total parenteral nutrition
TSAb
Thyroid stimulating antibodies
TSH
Thyroid stimulating hormone
UA
urinalysis
ULN
upper limit of normal
US
United States
USPI
United States prescribing information
Vss
volumes of distribution at steady-state
Vz
volume of distribution
Vz/F
apparent volume of distribution
WBC
white blood cell
WOCBP
Woman of child bearing potential


PF-06755347 
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PFIZER CONFIDENTIAL
Page 139
11. REFERENCES
1.
Hugues RA, Donofrio P, Bril V, et al. Intravenous immune globulin (10% 
caprylatechromatography purified) for the treatment of chronic inflammatory 
demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled 
trial. Lancet Neurol 2008; 7(2):136-44.-
2.
Lunemann JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in 
neurology--mode of action and clinical efficacy. Nat Rev Neurol 2015; 11(2):80-9.
3.
Lin HH, Wang MX, Spies JM, et al. Effective treatment of experimental autoimmune 
neuritis with Fc fragment of human immunoglobulin. J Neuroimmunol 2007; 
186(1-2):133-40.
4.
Niknami M, Wang MX, Nguyen T, et al. Beneficial effect of a multimerized 
immunoglobulin Fc in an animal model of inflammatory neuropathy (experimental 
autoimmune neuritis). J Peripher Nerv Syst 2013; 18(2):141-52.
5.
Mahmood I, Green MD. Drug interaction studies of therapeutic proteins or monoclonal 
antibodies. J Clin Pharmacol 2007; 47(12):1540-54.
6.
Lee JI, Zhang L, Men AY, et al. CYP-mediated therapeutic protein-drug interactions: 
clinical findings, proposed mechanisms and regulatory implications. Clin 
Pharmacokinet 2010; 49(5):295-310.
7.
Evers R, Dallas S, Dickmann LJ, et al. Critical review of preclinical approaches to 
investigate cytochrome P450-mediated therapeutic protein drug-drug interactions and 
recommendations for best practices: a white paper. Drug Metab Dispos 2013; 
41(9):1598-1609.
8.
Andresen I, Kovarik JM, Spycher M, et al. Product equivalence study comparing the 
tolerability, pharmacokinetics, and pharmacodynamics of various human 
immunoglobulin-G formulations. J Clin Pharmacol 2000; 40(7):722-30.
9.
Grifols [Internet].  GAMUNEX-C prescribing information, 3/2017revision. [Cited 17 
September 2018]  Available from: https://www.gamunex-
c.com/documents/27482625/27482925/Gamunex-
C+Prescribing+Information.pdf/9258bd0f-4205-47e1-ab80-540304c1ff8e. 
10.
Zhou H, Olsen H, So E, et al. A fully recombinant human IgG1 Fc multimer (GL-2045) 
inhibits complement-mediated cytotoxicity and induces iC3b. Blood Advances 2017; 
1(8):504-515.
11.
Bagdasarian A, Tonetta S, Harel W, Mamidi R, Uemura Y. IVIG adverse reactions: 
potential role of cytokines and vasoactive substances. Vox Sang. 1998;74(2):74-82.


PF-06755347 
B7801001
Final Protocol Amendment 8, 25 July 2022
PFIZER CONFIDENTIAL
Page 140
12.
Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine 
release syndrome and neurologic toxicity associated with immune effector cells. Biol 
Blood Marrow Transplant 2019; 25(4):625-38.
13.
Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019;37 
Suppl 1:48-52., Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke 
FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of 
toxicities. Nat Rev Clin Oncol. 2018;15(1):47-62.
14.
Debre M, Bonnet MC, Fridman WH, et al. Infusion of Fc gamma fragments for 
treatment of children with acute immune thrombocytopenic purpura. Lancet 1993; 
342(8877):945-9.
15.
Doobaree IU, Nandigam R, Bennette D, et al; Thromboembolism in adults with primary 
immune thrombocytopenia: a systematic literature review and meta-analysis. Eur J 
Haematol. 2016;97(4):321–30.
16.
Markle JG, Fish EN. SeXX matters in immunity. Trends Immunol. 2014;35(3):97-104.
17.
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the 
investigation and management of primary immune thrombocytopenia. Blood Adv. 
2019;3(22):3780-817.
18.
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 
guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-66.
19.
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the 
investigation and management of primary immune thrombocytopenia. Blood Adv. 
2019;3(22):3780-817.

SAP_001.pdf: 
Protocol B7801001 (PF-06755347) Statistical Analysis Plan
Page 1 of 22
PFIZER CONFIDENTIAL
Protocol B7801001
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, 
PLACEBO-CONTROLLED, FIRST-IN-HUMAN TRIAL TO EVALUATE THE SAFETY, 
TOLERABILITY, AND PHARMACOKINETICS OF PF-06755347 AFTER SINGLE 
ASCENDING INTRAVENOUS INFUSIONS TO HEALTHY ADULT SUBJECTS
Statistical Analysis Plan 
(SAP)
Version:
1.0
Author: 
 (ECD Statistics)
Date:
10-July-2017
PPD


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PFIZER CONFIDENTIAL
Revision History
Version
Date
Author(s)
Summary of Changes/Comments
1.0
July 10, 2017
Original
NOTE: Italicized text within this document has been taken verbatim from the Protocol.
PPD


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PFIZER CONFIDENTIAL
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................5
LIST OF FIGURES ...................................................................................................................5
APPENDICES ...........................................................................................................................5
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................6
2. INTRODUCTION .................................................................................................................6
2.1. Study Design .............................................................................................................6
2.2. Study Objectives .......................................................................................................9
2.2.1. Primary Objectives .......................................................................................9
2.2.2. Secondary Objectives ...................................................................................9
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................9
4. HYPOTHESES AND DECISION RULES...........................................................................9
4.1. Statistical Hypotheses ...............................................................................................9
4.2. Statistical Decision Rules..........................................................................................9
5. ANALYSIS SETS ...............................................................................................................10
5.1. Full Analysis Set .....................................................................................................10
5.2. Pharmacokinetic Analysis Set.................................................................................10
5.2.1. Concentration Analysis Set.........................................................................10
5.2.2. Parameter Analysis Set...............................................................................10
5.3. Pharmacodynamic Analysis Set..............................................................................10
5.4. Safety Analysis Set..................................................................................................10
5.5. Other Analysis Sets .................................................................................................10
5.6. Treatment Misallocations........................................................................................10
5.7. Protocol Deviations.................................................................................................10
5.7.1. Deviations Assessed Prior to Randomization.............................................11
5.7.2. Deviations Assessed Post-Randomization..................................................11
6. ENDPOINTS AND COVARIATES ...................................................................................11
6.1. Efficacy Endpoint(s) ...............................................................................................11
6.2. Safety Endpoints .....................................................................................................11
6.2.1. Adverse Events...........................................................................................11
6.2.2. Laboratory Safety Tests..............................................................................11
6.2.3. Vital Signs ..................................................................................................12
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6.2.4. ECG and Telemetry....................................................................................12
6.2.5. Other Safety Data .......................................................................................13
6.3. Pharmacokinetic Endpoints.....................................................................................13
6.4. PD Endpoints...........................................................................................................14
6.6. Other Endpoints.......................................................................................................14
6.6.1. Immunogenicity (ADA)..............................................................................14
6.7. Covariates................................................................................................................14
7. HANDLING OF MISSING VALUES ................................................................................14
7.1. Concentrations Below the Limit of Quantification.................................................15
7.2. Deviations, Missing Concentrations and Anomalous Values .................................15
7.3. Pharmacokinetic Parameters ...................................................................................15
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................15
8.1. Statistical Methods ..................................................................................................15
8.2. Statistical Analyses .................................................................................................15
8.2.1. Pharmacokinetic Analysis ..........................................................................15
8.3. Safety Analysis........................................................................................................17
8.3.1. Treatment and Disposition of Subjects.......................................................17
8.3.2. Demographic Data......................................................................................17
8.3.3. Discontinuation(s).......................................................................................17
8.3.4. Adverse Events...........................................................................................18
8.3.5. Laboratory Data..........................................................................................18
8.3.6. Vital Signs Data..........................................................................................18
8.3.7. ECG and Telemetry Data............................................................................18
8.3.8. Other Safety Data .......................................................................................19
8.3.9. Concomitant Treatments.............................................................................19
8.3.10. Screening and Other Special Purpose Data ..............................................19
 
9. REFERENCES ....................................................................................................................21
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LIST OF TABLES
Table 1.
Non-compartmental PK Parameters .....................................................................13
Table 2.
PK Parameters to be Summarized Descriptively..................................................16
LIST OF FIGURES
Figure 1 Sample Study Schematic..............................................................................................8
APPENDICES
Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern .....22


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PFIZER CONFIDENTIAL
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
PF-06755347 is a recombinant human IgG1 multimeric Fc fusion protein which includes the
IgG1 hinge region, the CH2, and CH3 domains, with a human IgG2 hinge domain fused onto
the C terminus. The molecule is designed to form Fc multimers, in order to enhance avidity
to Fcreceptors (FcRs).
The current study is the first clinical trial proposed with PF-06755347.  It is designed to 
evaluate the safety, tolerability, pharmacokinetics (PK), as well as potential 
pharmacodynamic (PD) effect of PF-06755347 following single intravenous (IV) doses of 
PF-06755347 to healthy adult subjects.
2.1. Study Design
This is a Phase 1, randomized, double-blind (Investigator and subject-blind, sponsor-open), 
placebo-controlled, parallel, single-ascending dose study of PF-06755347 in healthy 
subjects, to be conducted at a Pfizer Clinical Research Unit (CRU) that is in very close 
proximity to a major medical center. Personnel, trained in advanced cardiac life support, 
emergency resuscitative equipment and the management of anaphylaxis, are immediately 
available to treat systemic reactions under the supervision of a physician. IV fluids, 
epinephrine, antihistamine and methylprednisolone will be available for immediate 
parenteral use in the event of an anaphylactic reaction. In addition, a dedicated ambulance 
will be present at the research unit during dosing to facilitate rapid transfer to the 
Emergency Department of a major medical center, if needed.
The study will include 8 planned cohorts, with a provisional ninth cohort optionally added to 
explore or enhance the understanding of the full dose range. An optional Japanese cohort 
(Cohort 10) is also included.  The optional Cohort 9 and Cohort 10 may or may not be 
conducted pending evaluation of available safety and PK data from other cohorts and at the 
discretion of the Sponsor.
A total of approximately 73 healthy adult subjects are planned to be randomized. Fewer 
subjects (N=5, 3 active and 2 placebo) are planned for Cohorts 1-3, which are expected to 
have plasma exposure below the predicted efficacious concentration range (ie, doses 
1 mg/kg). For Cohorts 4-9 with expected plasma exposure near or exceeding predicted 
efficacious concentration range (ie, doses >1 mg/kg), a total of 9 subjects (6 active and 
3 placebo) is planned.  If pharmacological activity or exposure is significantly greater than 
expected, the sample size for Cohorts 1-3 may be increased to 9 subjects at the discretion of 
the Sponsor in consultation with the PI.  A total of 4 active subjects are planned for  the 
optional Japanese cohort. A schematic of the overall study design is provided in Figure 1.


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PFIZER CONFIDENTIAL
The subjects within each cohort (except for the Japanese cohort) will be dosed using a 
sentinel dosing strategy with sequential block design (diagramed in Figure 1). Each cohort 
will consist of 2 or 3 blocks, depending on the cohort sample size, with a monitoring period 
of at least72 hours between the dosing initiation in consecutive blocks. The number of 
subjects will increase sequentially, from 1 active and 1 placebo for the first block to 2 active 
and 1 placebo for the second block and  3 active and 1 placebo for the third block. For 
Cohorts 1-3, only the first and second blocks will be employed. The progression of dosing to 
the next block will occur if the dose is determined to be safe and well tolerated in the 
previous block by the PI. This sentinel dosing scheme will not be applied to the Japanese 
cohort, as the dose for this cohort, if conducted, will be a dose less than or equivalent to a 
dose studied in previous cohorts and deemed safe and well tolerated. 
Screening evaluation will occur within 28 days prior to dosing. Eligible subjects who meet 
the entry criteria will be admitted into the CRU on Day -1 and are required to stay overnight 
through completion of Day 8 evaluations.  Subjects will then return for outpatient visits per 
the Schedule of Activities through approximately Day 36 (1 mg/kg dose level) or Day 71 
(>1 mg/kg dose level) for a total of approximately 5 or 10 weeks study participation. 
respectively from first dose to follow-up, excluding screening. The follow-up period may be 
extended for a cohort block if any subject in the particular cohort block tests positive for 
anti-drug antibody to PF-06755347 at the scheduled follow-up visit, or has detectable 
concentration of PF-06755347 at final follow-up visit.
If a subject discontinues during the trial, the subject may be replaced at the discretion of the 
Sponsor in consultation with the PI.  Doses in the dose escalation sequence may be repeated 
or adjusted depending on the results obtained during the study to explore different doses 
and/or infusion/dosing rates as needed. The total number of cohorts including the optional 
Japanese cohort will not exceed 10.


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PFIZER CONFIDENTIAL
Figure 1 Sample Study Schematic
Optional 
Cohort 10 (N=4)
Japanese cohort
Dose TBD
Block 
1
Cohort 1 (N=5)
0.1 mg/kg
Block 
2
Block 
1
Cohort 2 (N=5)
0.3 mg/kg
Block 
2
Block 
1
Cohort 3 (N=5)
1 mg/kg
Block 
2
Block 
1
Cohort 4 (N=9)
3 mg/kg
Block 
2
Block 
3
Block 
1
Cohort 5 (N=9)
7.5 mg/kg
Block 
2
Block 
3
Block 
1
Cohort 6 (N=9)
15 mg/kg
Block 
2
Block 
3
Block 
1
Cohort 7 (N=9)
30 mg/kg
Block 
2
Block 
3
Block 
1
Cohort 8 (N=9)
45 mg/kg
Block 
2
Block 
3
Block 
1
Optional 
Cohort 9 (N=9)
Dose TBD
Block 
2
Block 
3
Within cohort sequential dosing scheme
Block 1 
(1 active + 
1 placebo)
Block 2 
(2 active + 
1 placebo)
Block 3 
(3 active + 
1 placebo)
Note: There will be a safety monitoring period 
of at least 72 hours between dosing initiation 
in consecutive blocks within the same cohort


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PFIZER CONFIDENTIAL
2.2. Study Objectives
2.2.1. Primary Objectives

To evaluate safety and tolerability of single IV escalating doses of PF-06755347 in 
healthy adult subjects.
2.2.2. Secondary Objectives

To characterize the plasma PK profile of PF-06755347 following single ascending IV 
infusions in healthy adult subjects.

To evaluate the immunogenicity profile of PF-06755347 following single ascending 
IV infusions in healthy adult subjects.
 
 
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
Safety and pharmacokinetic (PK) data will be reviewed after each cohort.
This is a sponsor open study, with the investigators and subjects blinded to study treatment. 
Specific Pfizer personnel (e.g. analytical staff, medical monitor, clinician, statistician, and
clinical pharmacologist) will be unblinded to subject treatments in order to permit real-time 
interpretation of the safety and pharmacokinetic data, and to provide information necessary 
to potentially alter the dose escalation sequence.  To minimize the potential for bias, 
treatment randomization information will be kept confidential by Pfizer personnel and will 
not be released to the investigator/study staff until the conclusion of the study.  Unblinding 
will not be performed until the final database has been locked for all cohorts.  Final analysis 
will follow the official database release.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No hypotheses are required.
4.2. Statistical Decision Rules
No decision rules are required.
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5. ANALYSIS SETS
5.1. Full Analysis Set
In general, the full analysis set is comprised of all randomized subjects. This population of 
subjects is not applicable for this study. Analysis sets for PK, safety and 
data are 
defined in Sections 5.2, 5.4 and 5.5.
5.2. Pharmacokinetic Analysis Set
5.2.1. Concentration Analysis Set
The PK concentration population is defined as randomized subjects who received at least 
one dose and have at least 1 concentration.
5.2.2. Parameter Analysis Set
The PK parameter analysis population is defined as all randomized subjects who received at 
least one dose and have at least 1 of the PK parameters of interest.
5.3. Pharmacodynamic Analysis Set
The PD analysis population is defined as all randomized subjects treated who have at least 
one PD assessment in at least one cohort.
5.4. Safety Analysis Set
All subjects who receive at least 1 dose of study medication will be included in the safety 
analyses and listings.
5.5. Other Analysis Sets
 
5.6. Treatment Misallocations
All analyses will be performed on an “as-treated” basis and will not include data from 
subjects who are randomized but not treated.  
If a subject takes a treatment that is not consistent with the treatment they are randomized to 
then they will be reported under the treatment that they actually receive for all safety, PK and 
 where applicable.
5.7. Protocol Deviations
Subjects who experience events that may affect their PK profile (eg dosing error) may be 
excluded from the PK analysis.  At the discretion of the pharmacokineticist a concentration 
value may also be excluded if the deviation in sampling time is of sufficient concern or if the 
concentration is anomalous for any other reason.  
A full list of protocol deviations will be compiled and reviewed to identify major and minor 
deviations prior to database closure.
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5.7.1. Deviations Assessed Prior to Randomization
At screening, the investigator will assess subjects against the inclusion and exclusion criteria 
as set out in Sections 4.1 and 4.2 of the protocol.
5.7.2. Deviations Assessed Post-Randomization
Any significant deviation from the protocol will be reviewed prior to database closure and a 
decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
None.
6.2. Safety Endpoints
In this section, the safety endpoints that will be measured during the study are detailed.  
Where applicable, details of the endpoints to be derived and definition of baseline are also 
provided.
The following data are considered in standard safety summaries (see protocol for collection 
days and list of parameters):

adverse events;

laboratory data;

vital signs data;

ECG and telemetry results.
6.2.1. Adverse Events
Any events occurring following start of treatment or increasing in severity will be counted as 
treatment emergent. 
Events that occur in a non-treatment period (for example, washout or follow-up) will be 
counted as treatment emergent and attributed to the previous treatment taken.
6.2.2. Laboratory Safety Tests
Safety laboratory tests will be performed as described in the protocol.
To determine if there are any clinically significant laboratory abnormalities, the 
haematological, clinical chemistry (serum) and urinalysis safety tests will be assessed against 
the criteria specified in the sponsor reporting standards. The assessment will take into 
account whether each subject’s baseline test result is within or outside the laboratory 
reference range for the particular laboratory parameter.
Baseline will be defined as the measurement on Day -1, or the last available pre-dose 
collection time point (whichever occurs later).


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6.2.3. Vital Signs
Triplicate vital signs measurement will be taken at pre-dose only. Single supine blood 
pressure, oral temperature, and pulse rate measurements will be taken at times detailed in the 
Schedule of Activities given in the protocol.  
Baseline will be defined as the mean of the replicated pre-dose (0 hours) measurement on 
Day 1.
The following vital signs endpoints will be determined:

Change from baseline in supine systolic and diastolic blood pressure, oral temperature
and pulse rate.

The maximum decrease and increase from baseline over all measurements taken post-
dose for supine systolic and diastolic blood pressures, oral temperature and pulse rate.
The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each post-dose measurement to give the change from baseline. The maximum of 
these values over the respective period will then be selected, except in the case where a 
subject does not show an increase.  In such an instance, the minimum decrease should be 
taken.
Similarly, the maximum decrease from baseline will be determined by selecting the 
minimum value of the changes from baseline. In cases where a subject does not show a 
decrease, the minimum increase should be taken.
6.2.4. ECG and Telemetry
ECG
A single 12-lead ECG will be obtained on all subjects at screening and follow-up.
12-lead ECGs will be recorded in triplicate on all subjects at all other time points as detailed 
in the Schedule of Activities given in the protocol.
The QT, heart rate, QTcF, PR, RR and QRS will be recorded at each assessment time.
If not supplied, QTcF will be derived using Fridericia’s heart rate correction formula:
QTcF = QT / (RR)1/3
where RR = 60/HR (if not provided)
The average of the triplicate readings collected at each assessment time will be calculated for
each ECG parameter.  Baseline will be defined as the average of the triplicate pre-dose 
recordings collected at 0 hours on Day 1.
The maximum absolute value (post-dose) and the maximum increase from baseline for QT, 
heart rate, QTcF, PR and QRS, will be determined over the first 24 hours post-dose for Day 
1, and also over all measurements taken post-dose for QTcF, PR and QRS.


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The maximum increase from baseline will be calculated by first subtracting the baseline 
value from each post-dose measurement to give the change from baseline.  The maximum of 
these values over the respective period will then be selected, except in the case where a 
subject does not show an increase.  In such an instance, the minimum decrease should be 
taken.
Changes from baseline for the ECG parameters QT interval, heart rate, QTcF interval, PR 
interval, and QRS interval will also be calculated.
Telemetry
All abnormal rhythms will be recorded and reviewed by the study physician for the presence 
of rhythm of potential clinical concerns, which will document the time, duration and 
description of the clinically significant event. 
6.2.5. Other Safety Data
Additional safety data will be collected as described in the protocol and will be listed if 
collected in the sponsor’s database.
6.3. Pharmacokinetic Endpoints
Blood samples for PK analysis of PF-06755347 will be taken according to the Schedule of 
Activities given in the protocol. 
The following PK parameters will be calculated for PF-06755347 from the concentration-
time values using standard non-compartmental methods:
Table 1.
Non-compartmental PK Parameters
Parameter
Analysis Scale
PF-06755347
Cmax
ln
D
Cmax (dn)
ln
D
Tmax
R
D
t1/2
*
R
D
AUClast
ln
D
AUClast (dn)
ln
D
AUCinf
*
ln
D
AUCinf
* (dn)
ln
D
CL*
ln
D
Vss
*
ln
D
Key:
A=analyzed using statistical model, D=displayed with descriptive statistics,
ln=natural-log transformed, R=raw (untransformed), *=if data permits


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6.4. PD Endpoints
None.
 
 
 
 
 
 
 
 
 
 
6.6. Other Endpoints
6.6.1. Immunogenicity (ADA)
Response rates of the development of anti-PF-06755347 antibodies (ADA).
Definitions for positive ADA will be determined with the completion of the valdiation work 
for the assay and may be included in an amendment to this SAP prior to final database lock.
6.7. Covariates
None.
7. HANDLING OF MISSING VALUES
For the analysis of safety endpoints, the sponsor data standard rules for imputation will be 
applied.
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7.1. Concentrations Below the Limit of Quantification
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification). For PK calculations, 
BLQ will be handled by the Pfizer standard processes.
7.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of median profiles, statistics will be calculated having set 
concentrations to missing if 1 of the following cases is true:
A concentration has been collected as ND (ie not done) or NS (ie no sample);
A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
7.3. Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a subject’s concentration data, the parameter will 
be coded as NC (ie not calculated). (Note that NC values will not be generated beyond the 
day that a subject discontinues.)
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will be presented for a particular dose with ≥3 evaluable measurements.
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as dosing error), this will be footnoted in summary tables and will 
not be included in the calculation of summary statistics or statistical analyses.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical Methods
As this is an 
 study, no formal hypothesis testing will be performed.
8.2. Statistical Analyses
8.2.1. Pharmacokinetic Analysis
To assess the pharmacokinetics of PF-06755347, the PK parameters detailed in Section 6.3 
will be listed and summarized for subjects in the PK analysis set (as defined in Section 
5.2.2). Missing values will be handled as detailed in Section 7. Each PK parameter will be 
summarized by dose. Optional Cohort 10 Japanese (if applicable) will be analysed separately. 
Each summary will include the set of summary statistics as specified in Table 2.
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Table 2.
PK Parameters to be Summarized Descriptively
Parameter
Summary Statistics
AUClast, AUCinf, 
Cmax, Cmax(dn), 
AUClast(dn), 
AUCinf(dn), CL, Vss, 
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum, geometric mean and geometric cv%.
Tmax
N, median, minimum, maximum.
t1/2
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum.
There will be one summary table split by dose presenting all PK parameters.
To assess the relationship between the PK parameters and dose, dose normalized AUCinf (if 
data permit), AUClast and Cmax will be plotted against dose (using a logarithmic scale), and 
will include individual subject values and the geometric means for each dose separately.  
Geometric means will have a different symbol than the individual values.  The values will be 
dose normalized (to a 1 mg dose) by dividing the individual values and raw geometric means 
by dose.  A footnote will be added to the plots to indicate that geometric means are 
presented.
Supporting data from the estimation of t½ and AUCinf will be listed where applicable: 
terminal phase rate constant (kel); goodness of fit statistic from the log-linear regression (r2); 
the percent of AUCinf based on extrapolation (AUCextrap%); and the first, last, and number of 
time points used in the estimation of kel. These data may be included in the clinical study 
report.
Presentations for PF-06755347 concentrations will include:

A listing of all concentrations sorted by subject ID, dose, and nominal time post-dose.  
The concentration listing will also include the actual times.  Deviations from the nominal 
time will be given in a separate listing.

A summary of concentrations by dose, cohort, and nominal time post-dose, where the set 
of statistics will include n, mean, median, standard deviation, coefficient of variation 
(cv), minimum, maximum and the number of concentrations above the lower limit of 
quantification.

Median concentrations time plots (on both linear and semi-log scales) against nominal 
time post-dose by dose and cohort (all doses on the same plot per scale, based on the
summary of concentrations by dose, cohort and time post-dose). 

Mean concentrations time plots (on both linear and semi-log scales) against nominal time 
post-dose by dose and cohort (all doses on the same plot per scale, based on the summary 
of concentrations by dose, cohort and time post-dose). 


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The length of time used for the x-axes of these plots will be decided on review of the data, 
and will depend on how long PF-06755347 concentration is quantifiable in the matrix.
For summary statistics, median and mean plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used.
Subjects having positive ADA may be analyzed separately to assess impact of ADA on PK 
concentrations and if no effect then those subjects will be included in the summarized PK 
concentration and parameter descriptive statistics. Refer to Section 8.3.8 for more details.
8.3. Safety Analysis
A set of summary tables split by treatment will be produced to evaluate any potential risk 
associated with the safety and toleration of administering PF-06755347. The optional Cohort 
10 (if applicable) will be presented separately. 
No formal analyses are planned for safety data.  The safety and other endpoints detailed in 
Section 6.2 will be listed and summarized in accordance with sponsor reporting standards, 
where the resulting data presentations will consist of subjects from the safety analysis set (as 
defined in Section 5.4).
8.3.1. Treatment and Disposition of Subjects
Subject evaluation groups will show end of study subject disposition and will show which 
subjects were analyzed for pharmacokinetics, as well as for safety (adverse events and 
laboratory data).  Frequency counts will be supplied for subject discontinuation(s) by 
treatment. Japanese subjects in Cohort 10 (if applicable) will be summarized separately from 
the subjects in other cohorts.
Data will be reported in accordance with the sponsor reporting standards.
8.3.2. Demographic Data
A break down of demographic data will be provided for age, race, ethnicity, weight, body 
mass index and height.  Each will be summarized by sex at birth and ‘All Subjects’ for each 
cohort separately and overall in accordance with the sponsor reporting standards.
8.3.3. Discontinuation(s)
Subject discontinuations, temporary discontinuations or dose reductions due to adverse 
events will be detailed and summarized by treatment.
Data will be reported in accordance with the sponsor reporting standards.


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8.3.4. Adverse Events
Adverse events will be reported in accordance with the sponsor reporting standards.
8.3.5. Laboratory Data
Laboratory data will be listed and summarized by treatment, which will be reported 
separately for Cohort 10 (if applicable) in accordance with the sponsor reporting standards.  
Baseline is as defined in Section 6.2.2.
8.3.6. Vital Signs Data
Absolute values and changes from baseline in supine systolic and diastolic blood pressure,
oral temperature, and pulse rate will be summarized by treatment and Cohort 10 (if 
applicable) in accordance with the sponsor reporting standards.  Tables will be paged by 
parameter.  Baseline is as defined in Section 6.2.3.
Mean changes from baseline for supine systolic and diastolic blood pressure, oral 
temperature, and pulse rate for each treatment will be plotted against time post-dose. On each 
plot there will be 1 line for each treatment, with separate plots Cohort 10 (if applicable).  
Corresponding individual plots of changes from baseline will also be produced for each 
treatment.
Maximum absolute values and changes from baseline for vital signs will also be summarized 
descriptively by treatment , separately for Cohort 10 (if applicable), using categories as 
defined in Appendix 1. Numbers and percentages of subjects meeting the categorical criteria 
will be provided. All planned and unplanned post-dose timepoints will be counted in these 
categorical summaries. All values meeting the criteria of potential clinical concern will be 
listed.
8.3.7. ECG and Telemetry Data
ECG
Absolute values and changes from baseline in QT, heart rate, QTcF, PR and QRS will be 
summarized by treatment, which will be reported separately for Cohort 10 (if applicable) in 
accordance with the sponsor reporting standards.  Tables will be paged by parameter.
Baseline is as defined in Section 6.2.4.
Mean changes from baseline in QT, heart rate and QTcF will be plotted against time post-
dose.  On each plot there will be 1 line for each treatment. Corresponding individual plots of 
changes from baseline will also be produced for each treatment.
Changes from baseline in QTcF will also be plotted separately against drug concentrations.  
This will be a scatter plot for all observations where QTcF and drug concentration are 
recorded. Placebo data will also be included (with drug concentration set to zero).  Different 
symbols will be used for each treatment. There will be a separate plot for Cohort 10 (if 
applicable).


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Maximum increase from baseline for QTcF, heart rate, QT, PR and QRS will be summarized 
by treatment, separately for Cohort 10 (if applicable) in accordance with the sponsor 
reporting standards. 
ECG endpoints and changes from baseline (QTcF, PR and QRS) will also be summarized 
descriptively by treatment, separately for Cohort 10 (if applicable), using categories as 
defined in Appendix 1 (for QTc these correspond to ICH E141).  Numbers and percentages of 
subjects meeting the categorical criteria will be provided.  All planned and unplanned post-
dose timepoints will be counted in these categorical summaries.  All values meeting the 
criteria of potential clinical concern will be listed.
Listings of subjects with any single post-dose value 500 msec will also be produced for 
QTcF.
Telemetry
Telemetry data will be listed for those subjects with abnormal rhythms, showing the 
treatment, time, duration and description of the clinically significant event.
8.3.8. Other Safety Data
The percentage of subjects with positive ADA will be summarized by dose and presented 
separately for Cohort 10 (if applicable). For subjects with positive ADA, the magnitude 
(titer), time of onset, and duration of ADA response will also be described, if data permit. 
The impact of ADA on PK and/or safety may also be assessed, if data permit.This may 
include:

Spaghetti plots of individual PF-06755347 concentration time profile, grouped by 
ADA status, produced separately by treatment and for Cohort 10 (if applicable).

Table summaries of PK parameters (AUCinf , AUClast and Cmax) by ADA status, 
presented separately for Cohort 10 (if applicable).
8.3.9. Concomitant Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the 
listings.
8.3.10. Screening and Other Special Purpose Data
Prior medication(s) and non-drug treatment(s) and FSH concentrations for all females of 
childbearing potential and urine drug screen will be obtained at Screening.
These data will not be brought in-house, and therefore will not be listed.
Any other screening data that is captured in the study database will be listed.


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CCI


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9. REFERENCES
1.
ICH E14 - The clinical evaluation of QT/QTc interval prolongation and proarrhythmic 
potential for non-antiarrhythmic drugs.  CHMP/ICH/2/04.


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Appendix 1. Categorical Classes for ECG and Vital Signs of Potential Clinical Concern
Categories for QTcF
QTcF (ms)
450< max. ≤480
480< max. ≤500
max. >500
QTcF (ms) 
increase from 
baseline
30< max. ≤60
max. >60
Categories for PR and QRS
PR (ms)
max. ≥300
PR (ms) increase 
from baseline
Baseline >200 
and max. 
≥25% increase
Baseline ≤200 and 
max. ≥50% 
increase
QRS (ms)
max. ≥140
QRS (ms) 
increase from 
baseline
≥50% increase
Categories for Vital Signs
Systolic BP (mm Hg)
min. <90
Systolic BP (mm Hg) 
change from baseline
max. decrease ≥30
max. increase ≥30
Diastolic BP (mm Hg)
min. <50
Diastolic BP (mm Hg) 
change from baseline
max. decrease ≥20
max. increase ≥20
Supine pulse rate (bpm)
min. <40
max. >120
Measurements that fulfill these criteria are to be listed in report.