Clinical trial NCT05037409
Conditions: Healthy
Sponsor: Pfizer
Start date: 2021-09-28; Completion date: 2022-03-27
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Purpose of the study is to evaluate the safety, tolerability, immunogenicity and pharmacokinetics (PK) of PF-06823859 following a single intravenous dose of PF-06823859 300 and 900 mg in Japanese healthy adult participants.

Detailed description:
Approximately 12 participants are planned to be enrolled into the study. The study consists of 2 cohorts, and approximately 5 participants will be randomized to PF-06823859 and approximately 1 participant will be randomized to placebo in each cohort.

Arms: arm 1: Participants will receive single intravenous infusion. arm 2: Participants will receive single intravenous infusion. arm 3: Participants will receive single intravenous infusion.
Interventions: intervention 1: PF-06823859 intervention 2: Placebo
Intervention descriptions: intervention 1: low dose or high dose intravenous infusion intervention 2: Intravenous infusion

Protocol documents:
Prot_000.pdf: 
PF-06823859
Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, IMMUNOGENICITY AND PHARMACOKINETICS 
FOLLOWING SINGLE INTRAVENOUS DOSE OF PF-06823859
IN JAPANESE HEALTHY PARTICIPANTS
Study Intervention Number:
PF-06823859
Study Intervention Name:
N/A
US IND Number:
N/A
EudraCT Number:
N/A
ClinicalTrials.gov ID:  
N/A
Protocol Number:
C0251005
Phase:
1
Brief Title: A Phase 1 Study to Evaluate the Safety, Tolerability, Immunogenicity and 
Pharmacokinetics of Single-Dose of PF-06823859 in Japanese Healthy Participants
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.


PF-06823859
Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
Page 2
Document History
Document
Version Date
Amendment 1
09 Jul 2021
Original protocol
26 May 2021
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any global protocol administrative 
clarification letter.
Protocol Amendment Summary of Changes Table
Amendment 1 (09-Jul-2021)
Overall Rationale for the Amendment:
Section # and 
Name
Description of Change
Brief Rationale
Section 5.2
Exclusion 
Criteria 6
Added descriptions that history of 
allergic or anaphylactic reaction to 
any components in the study 
intervention is also excluded.
To ensure participant’s safety.


PF-06823859
Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
Page 3
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ......................................................................................................................9
1.3. Schedule of Activities .............................................................................................10
2. INTRODUCTION ...............................................................................................................13
2.1. Study Rationale .......................................................................................................13
2.2. Background .............................................................................................................13
2.2.1. Nonclinical Overview.................................................................................13
2.2.2. Clinical Overview.......................................................................................14
2.2.2.1. Safety.........................................................................................14
2.2.2.2. Pharmacokinetics ......................................................................14
2.2.2.3. Immunogenicity ........................................................................15
2.3. Benefit/Risk Assessment.........................................................................................15
3. OBJECTIVES AND ENDPOINTS.....................................................................................16
4. STUDY DESIGN.................................................................................................................16
4.1. Overall Design.........................................................................................................16
4.2. Scientific Rationale for Study Design.....................................................................17
4.2.1. Choice of Contraception/Barrier Requirements .........................................18
4.2.2. Collection of Retained Research Samples..................................................18
4.3. Justification for Dose ..............................................................................................18
4.4. End of Study Definition ..........................................................................................19
5. STUDY POPULATION......................................................................................................19
5.1. Inclusion Criteria.....................................................................................................19
5.2. Exclusion Criteria....................................................................................................20
5.3. Lifestyle Considerations..........................................................................................23
5.3.1. Meals and Dietary Restrictions...................................................................23
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................23
5.3.3. Activity .......................................................................................................23
5.3.4. Contraception..............................................................................................23


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5.4. Screen Failures ........................................................................................................24
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................24
6.1. Study Intervention(s) Administered........................................................................24
6.1.1. Administration............................................................................................24
6.1.1.1. Intravenous Infusion Discontinuation .......................................25
6.2. Preparation, Handling, Storage, and Accountability...............................................25
6.2.1. Preparation and Dispensing........................................................................26
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................26
6.3.1. Allocation to Study Intervention ................................................................26
6.3.2. Breaking the Blind......................................................................................27
6.4. Study Intervention Compliance...............................................................................27
6.5. Dose Modification...................................................................................................28
6.6. Continued Access to Study Intervention After the End of the Study......................28
6.7. Treatment of Overdose............................................................................................28
6.8. Concomitant Therapy..............................................................................................28
6.8.1. Rescue Medicine.........................................................................................29
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................29
7.1. Discontinuation of Study Intervention ....................................................................29
7.2. Participant Discontinuation/Withdrawal From the Study.......................................29
7.2.1. Withdrawal of Consent...............................................................................30
7.3. Lost to Follow up ....................................................................................................30
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................30
8.1. Efficacy Assessments..............................................................................................32
8.2. Safety Assessments .................................................................................................32
8.2.1. Physical Examinations................................................................................32
8.2.2. Chest X-ray.................................................................................................32
8.2.3. Vital Signs ..................................................................................................32
8.2.3.1. Temperature ..............................................................................33
8.2.4. Electrocardiograms.....................................................................................33
8.2.5. Infusion Site Assessment............................................................................34
8.2.6. Clinical Safety Laboratory Assessments ....................................................34


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8.2.6.1. HBV testing...............................................................................34
8.2.7. Tuberculosis test .........................................................................................35
8.2.8. Viral Surveillance .......................................................................................36
8.2.9. COVID-19 Specific Assessments...............................................................36
8.2.10. Pregnancy Testing ....................................................................................36
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................37
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......37
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................38
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................38
8.3.2. Method of Detecting AEs and SAEs ..........................................................38
8.3.3. Follow-Up of AEs and SAEs......................................................................38
8.3.4. Regulatory Reporting Requirements for SAEs...........................................39
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................39
8.3.5.1. Exposure During Pregnancy......................................................39
8.3.5.2. Exposure During Breastfeeding ................................................41
8.3.5.3. Occupational Exposure .............................................................41
8.3.6. Cardiovascular and Death Events...............................................................42
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................42
8.3.8. Adverse Events of Special Interest.............................................................42
8.3.8.1. Lack of Efficacy........................................................................42
8.3.9. Medical Device Deficiencies......................................................................42
8.3.10. Medication Errors.....................................................................................42
8.4. Pharmacokinetics ....................................................................................................43
8.7. Immunogenicity Assessments.................................................................................44
8.8. Health Economics ...................................................................................................45
9. STATISTICAL CONSIDERATIONS ................................................................................45
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9.1. Statistical Hypotheses .............................................................................................45
9.2. Analysis Sets ...........................................................................................................45
9.3. Statistical Analyses .................................................................................................46
9.3.1. General Considerations...............................................................................46
9.3.2. Primary Endpoint(s)....................................................................................46
9.3.2.1. Electrocardiogram (ECG) Analysis...........................................47
9.3.3. Secondary Endpoint(s)................................................................................47
9.3.3.1. Pharmacokinetic Analyses ........................................................47
9.3.3.2. Immunogenicity Analyses.........................................................48
9.3.4. Other Safety Analyses ................................................................................48
9.4. Interim Analyses .....................................................................................................49
9.5. Sample Size Determination.....................................................................................49
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................50
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............50
10.1.1. Regulatory and Ethical Considerations ....................................................50
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................50
10.1.2. Informed Consent Process ........................................................................51
10.1.3. Data Protection .........................................................................................52
10.1.4. Committees Structure ...............................................................................52
10.1.4.1. Data Monitoring Committee ...................................................52
10.1.5. Dissemination of Clinical Study Data ......................................................52
10.1.6. Data Quality Assurance ............................................................................53
10.1.7. Source Documents....................................................................................54
10.1.8. Study and Site Start and Closure ..............................................................55
10.1.9. Publication Policy.....................................................................................56
10.1.10. Sponsor’s Qualified Medical Personnel .................................................56
10.2. Appendix 2: Clinical Laboratory Tests .................................................................58
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................59
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10.3.1. Definition of AE .......................................................................................59
10.3.2. Definition of an SAE ................................................................................60
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period............................................................................61
10.3.4. Reporting of SAEs....................................................................................65
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................66
10.4.1. Male Participant Reproductive Inclusion Criteria....................................66
10.4.2. Female Participant Reproductive Inclusion Criteria.................................66
10.4.3. Woman of Childbearing Potential ............................................................67
10.4.4. Contraception Methods.............................................................................68
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......71
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................73
10.8. Appendix 8: Abbreviations ...................................................................................75
11. REFERENCES ..................................................................................................................79
LIST OF TABLES
Table 1.
Randomization Scheme ............................................................................17
Table 2.
Serum PF-06823859 PK Parameters ........................................................48
Table 3.
Protocol-Required Safety Laboratory Assessments .................................58
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: A Phase 1 Study to Evaluate the Safety, Tolerability, Immunogenicity and 
Pharmacokinetics of Single-Dose of PF-06823859 in Japanese Healthy Participants.
Rationale
The purpose of this study is to evaluate the safety, tolerability, immunogenicity and PK of 
PF-06823859 after single IV administration to Japanese healthy adult participants. The 
information of safety, tolerability, immunogenicity and PK in Japanese healthy participants is 
being collected to support the development of PF-06823859 in Japan.
Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 

To evaluate the safety and tolerability of single 
IV dose of 300 and 900 mg PF-06823859 in 
Japanese healthy participants.

Assessments of AEs/SAEs including IRR, 
infusion sites and viral infections, vital signs, 
ECGs and laboratory tests.
Secondary: 
Secondary: 

To evaluate the PK profile of single IV dose of 
300 and 900 mg PF-06823859 in Japanese 
healthy participants.

To evaluate the immunogenicity of 
PF-06823859.

Serum PF-06823859 PK parameters, as 
permitted by data: Cmax, Cmax (dn), Tmax, AUCinf, 
AUCinf (dn), AUClast, AUClast (dn), AUC14day, 
AUC28day, t½, CL, Vss and MRT.

Incidence of the development of ADA and NAb.


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Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
Page 9
Overall Design
This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study to 
evaluate the safety, tolerability, immunogenicity and PK of PF-06823859 following a single 
intravenous dose of PF-06823859 300 and 900 mg in Japanese healthy adult participants.
Number of Participants
Approximately 12 participants are planned to be enrolled into the study. The study consists 
of 2 cohorts, and approximately 5 participants will be randomized to PF-06823859 and 
approximately 1 participant will be randomized to placebo in each cohort (Section 9.5).
Participants who discontinue prior to completion of the study for non-safety related reasons
may be replaced at the discretion of the investigator upon consultation with the sponsor.
Intervention Groups and Duration
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single IV infusion of PF-06823859 or placebo. The 
participants in Cohort 2 should be dosed following at least 96 hours safety pause after the 
participants in Cohort 1 has been dosed. Participants will be admitted into the CRU 
approximately 1 day prior to dosing and are required to stay overnight in the CRU through 
completion of Day 5 evaluations. Participants will return to the CRU for outpatient follow-up 
visits through Day 157.
Data Monitoring Committee or Other Independent Oversight Committee: No
Statistical Methods
Safety and tolerability data will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations.
Serum concentrations and serum PK parameters of PF-06823859 will be summarized 
descriptively.
1.2. Schema
Not applicable.


PF-06823859
Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
Page 10
1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Visit Identifiera
Abbreviations used in this table may be 
found in Appendix 8.
Screening
CRU Confinement
Follow-Up
ET
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
8
15
29
43
57
71
99
127
157
-
Visit Window (days)
-
-
-
-
-
-
-
1
3
3
3
3
3
3
3
3
-
Hours After Dose
0b
1
2
6
12
24
48
72
96
-
-
-
-
-
-
-
-
-
-
Informed consent
X
Demography
X
CRU confinement
X








X
Visit to the CRU
X
X








X
X
X
X
X
X
X
X
X
X
Inclusion/exclusion criteria
X
X
Medical/medication history (update) 
X
X
History of illegal drug & alcohol and 
tobacco use
X
X
Report prior or concomitant treatments
X
X









X
X
X
X
X
X
X
X
X
X
Contraception check
X
X








X
X
X
X
X
X
X
X
X
X
X
Physical exam (including height & body 
weight at screening, only)c
X
X
X
Single 12-Lead ECG
X
X
X
X
X
X
X
X
X
Supine BP, PR and oral or axillary 
temperature
X
X
X
X
X
X
X
X
X
Chest X-rayd
X
Serious and nonserious AE monitoring
X









X
X
X
X
X
X
X
X
X
X
X
Study intervention administration
Xe







Safety laboratory (after 4 hour fasting)
including PT, INR, aPTT
X
X
X
X
X
X
X
X
X
X
X
X
Viral surveillance (CMV, VZV, EBV, 
HHV6, HSV-1/2)
X
X
X
X
X
X
X


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Protocol C0251005
Final Protocol Amendment 1, 09 Jul 2021
PFIZER CONFIDENTIAL
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Visit Identifiera
Abbreviations used in this table may be 
found in Appendix 8.
Screening
CRU Confinement
Follow-Up
ET
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
8
15
29
43
57
71
99
127
157
-
Visit Window (days)
-
-
-
-
-
-
-
±1
±3
±3
±3
±3
±3
±3
±3
±3
-
Hours After Dose
0b
1
2
6
12
24
48
72
96
-
-
-
-
-
-
-
-
-
-
FSH in females amenorrheic ≥12 
months, only
X
Pregnancy test (WOCBP only)
X
X
X
X
X
X
X
X
X
X
HIV, HBsAg, HBsAb, HBcAb, HCVAb,
syphilis
X
HBV DNA, if applicablef
X
X
X
X
Interferon Gamma Release Assayg
X
COVID-19 questionnaireh
X
X
X
X
X
X
X
X
X
X
X
X
COVID-19 testingi
X
X
COVID-19 check temperaturej
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sampling
X
Xk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity (ADA, NAb)l
X
X
X
X
X
X
X
X
X
Urine drug testing
X
X
Urinalysis (after ≥4 hour fasting)
X
X
X
X
X
X
X
X
X
X
X
X
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Visit Identifiera
Abbreviations used in this table may be 
found in Appendix 8.
Screening
CRU Confinement
Follow-Up
ET
Days Relative to Day 1
-28 to -2
-1
1
2
3
4
5
8
15
29
43
57
71
99
127
157
-
Visit Window (days)
-
-
-
-
-
-
-
±1
±3
±3
±3
±3
±3
±3
±3
±3
-
Hours After Dose
0b
1
2
6
12
24
48
72
96
-
-
-
-
-
-
-
-
-
-
a.
Day relative to start of study intervention (Day 1).
b.
Pre-dose (except for study intervention administration)
c.
Physical examination may be performed at non-specified timings if there are findings during the previous examination or new/open AEs, if appropriate and at the 
discretion of the investigator.
d.
Chest X-ray or other appropriate diagnostic image (ie, CT or MRI) results within 12 weeks prior of the screening visit, otherwise a chest X-ray must be performed and 
results obtained prior to dosing in the study. See Section 8.2.2.
e.
Participants should be monitored from start of study intervention infusion until the end of infusion to assess the infusion site. See Section 8.2.5.
f.
Participants who are HBsAg negative, HBcAb negative and HBsAb positive without unequivocal documentation of prior HBV vaccination or who are HBsAg negative,
HBcAb positive and HBsAb positive are required to undergo HBV DNA reflex testing at screening. If HBV DNA is undetectable in the HBV DNA reflex testing at
screening and the participant is enrolled the study, HBV DNA testing must be performed on Day 71, 157 and ET. See Section 8.2.6.1.
g.
Additional TB testing is allowed at any time if requested by the investigator and/or if there is a suspicion of TB reactivation or new TB infection. See Section 8.2.7.
h.
Check exposure to positive subject, residence or travel in area of high incidence and COVID-19 related signs and symptoms. To be done at least 2 days before and at each 
visit.
i.
The testing for COVID-19 pathogen by PCR will be performed between Day -5 and Day -3 to permit availability of test result prior to admission on Day -1. A subsequent 
COVID-19 test will be performed if they develop COVID-19 like symptom.
j.
To be done at least daily during residence and at every follow-up visit after discharge from the CRU.
k.
End of infusion (ie, 1 hour post-dose)
l.
Participants with positive results may be requested to return for additional follow-up for up to approximately 3 months after final visit.
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2. INTRODUCTION
PF-06823859 is a potent, selective, humanized IgG1 neutralizing antibody directed against 
the human soluble cytokine IFN, a member of the type I IFN family of cytokines that is 
currently being developed for the treatment of SLE with added potential for therapeutic 
benefit in DM.
2.1. Study Rationale 
The purpose of the study is to investigate the safety, tolerability, immunogenicity and PK of 
PF-06823859 in Japanese healthy adult participants. The information of safety, tolerability, 
immunogenicity and PK in Japanese healthy participants is being collected to support the 
development of PF-06823859 in Japan.
2.2. Background 
DM is an acquired rare inflammatory disease classified as both a neuromuscular disease and 
an autoimmune disease. DM is characterized by a distinctive skin rash and muscle weakness 
or inflamed muscles. Symptoms can come on suddenly or gradually over time. It is thought 
that the inflammation resulting in cell damage is created when the immune system attacks 
healthy muscle tissue and blood vessels under the skin. DM is idiopathic; however, some 
individuals may have a genetic predisposition that is triggered by medications, viruses, 
bacteria, trauma, toxins, cancer or other illness. DM symptoms often wax and wane for no 
apparent reason and females are affected twice as often as males.1,2
DM has no known cure and there are no widely approved treatments. Patients typically use a 
combination of drugs to seek relief for their inflammatory symptoms. Typically, the first line 
of treatment for the muscle disease is corticosteroids to address the inflammation as well as 
suppress the immune system. Other immunosuppressive drugs, notably azathioprine, 
methotrexate, mycophenolate mofetil and cyclophosphamide are used as subsequent lines of 
therapies in refractory cases or as steroid-sparing agents.  However, complications of 
long-term steroid and immunosuppressive therapies are well documented.  Other novel 
approaches have emerged as potential treatment, including tacrolimus (broadly 
immunosuppressive drug developed for transplant use), intravenous immunoglobulin, and 
rituximab, following positive outcomes in some case studies. However, additional 
randomized controlled trials with these treatments are needed to guide clinical practice.3
Consequently, DM remains a disease with very high unmet medical need, and development 
of safe and effective therapies is warranted. 
2.2.1. Nonclinical Overview
Detailed information concerning the nonclinical studies conducted with PF-06823859 can be 
found in the SRSD, which for this study is the IB. Overall, these assessments indicate that 
PF-06823859 is a potent inhibitor of IFN/IFNAR signaling in human and cynomolgus 
monkey cells, and the data support the use of the cynomolgus monkey as a 
pharmacologically relevant species for nonclinical toxicity studies. Furthermore, the 
nonclinical safety profile of PF-06823859 has been adequately characterized in vitro and in 


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vivo in cynomolgus monkey to support progression into clinical trials up to 3 months in 
duration.
2.2.2. Clinical Overview
As of the protocol date, Phase 1, randomized, double-blind, third-party open, 
placebo-controlled, dose escalating study to evaluate the safety, tolerability, PK and PD of 
single and multiple IV and SC doses of PF-06823859 in healthy participants (C0251001) has
been completed. In addition, Phase 2a, randomized, double-blind, placebo-controlled study to 
evaluate the efficacy, safety, and tolerability of PF-06823859 in adult participants with DM 
(C0251002) is ongoing with no data available at this time.
Detailed information concerning the clinical studies conducted with PF-06823859 can be 
found in the SRSD, which for this study is the IB.
2.2.2.1. Safety
Data from Study C0251001 suggests that PF-06823859 was generally well tolerated and safe 
when given up to 2000 mg as single IV dose and up to 1800 mg given 600 mg IV Q2W × 3. 
The most common AE was upper respiratory tract infection, likely due to viral infection. No 
serious AE or death occurred during the study.
During the SAD period, all TEAEs reported were mild in severity. During the MAD period, 
while the majority of the TEAEs were mild in severity, 4 TEAEs were moderate in severity: 
2 TEAEs (abdominal pain upper and headache) in the placebo SC × 3 doses treatment group, 
1 TEAE (upper respiratory tract infection) in the PF-06823859 300 mg SC × 3 doses 
treatment group and 1 TEAE (sinusitis) in the PF-06823859 600 mg IV (Q4W) × 2 doses 
treatment group, none of which were considered by the investigator as treatment related.
One participant experienced a mild localized erythema with induration and tenderness after 
each of the 100 mg SC dosing with PF-06823859 administered Q2W for a total of 3 doses, 
but no signs or symptoms of a systemic reaction. These local reactions resolved without 
further intervention within a few days. This participant also had treatment-induced ADA, 
which had returned to baseline at the time of discharge (Section 2.2.2.3).
Overall, there was no apparent difference in the total rate of AEs between the participants 
treated with PF-06823859 compared to placebo and no apparent dose relationship with the 
doses of PF-06823859. However, the rate of mild upper respiratory tract infection appears to 
be higher in participants treated with PF-06823859.
There were no clinically significant observations in ECG, vital signs or laboratory 
abnormalities. 
2.2.2.2. Pharmacokinetics 
Following single IV administration of 30 mg to 2000 mg doses, PF-06823859 demonstrated a 
bi-phasic PK profile with a terminal half-life ranging from 22.73 to 29.08 days, slow CL 
(0.005953 to 0.006817 L/h) and small volume of distribution (4.828 to 6.013 L), all attributes 


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of a typical IgG1 molecule. Further, Tmax occurred around 1 hour after the end of the IV 
infusion, Cmax ranged from 10.81 to 708.3 µg/mL, and AUCinf ranged from 5042 to 
322,100 µg.h/mL. Both Cmax and AUCinf showed dose proportional increases across the 
30 mg to 2000 mg dose range.
Following multiple IV administration of PF-06823859 at either 600 mg dosing Q2W for a 
total of 3 doses or 600 mg dosing Q4W for a total of 2 doses, Cmax and Cav after last dose 
were 284.9 µg/mL and 181.6 µg/mL for 600 mg IV Q2W and 259.5 µg/mL and 109.6 µg/mL
for 600 mg IV Q4W. Rac (based on AUCτ) following 600 mg IV Q2W and 600 mg IV Q4W 
dosing on Day 29 were 1.893 and 1.407, respectively. Rac, Cmax (based on Cmax) was similar 
with a mean ratio of 1.079 for 600 mg IV Q2W dosing regimen and 1.298 for 600 mg IV 
Q4W dosing regimen.
Following multiple SC administration of PF-06823859 at either 100 mg or 300 mg dosing 
Q2W for a total of 3 doses, Cmax was reached moderately slow with median Tmax of 96 hours 
following the first SC dose on Day 1, and slightly earlier at 48 hours after the second dose 
(Day 15) and the third dose (Day 29), respectively. In addition, Cmax and Cav after last dose 
were 19.49 µg/mL and 18.11 µg/mL for 100 mg SC and 62.92 µg/mL and 54.26 µg/mL for 
300 mg SC. Rac (based on AUCτ) following 100 mg SC Q2W and 300 mg SC Q2W dosing
on Day 29 were 2.376 and 2.499, respectively. Rac, Cmax (based on Cmax) was similar with a 
mean ratio of 2.063 for 100 mg SC Q2W dosing regimen and 2.294 for 300 mg SC Q2W 
dosing regimen.
2.2.2.3. Immunogenicity
Among all 48 participants treated with PF-06823859 in Study C0251001, 6 participants 
tested positive for ADA (SAD: 2 participants at 30 mg IV and 1 participant at 900 mg IV; 
MAD: 1 participant each at 100 mg SC Q2W, 300 mg SC Q2W and 600 mg IV Q2W). Of 
these 6 participants, 1 participant at 100 mg SC developed treatment induced NAb.
2.3. Benefit/Risk Assessment
A single-dose of PF-06823859 is not expected to provide any clinical benefit to healthy 
participants. This study is designed primarily to generate safety, tolerability, immunogenicity
and PK data for further clinical development.
Nonclinical data to date (Section 2.2.1) has not identified any risk to reproductive organs in 
sexually mature cynomolgus monkeys, the pharmacologically relevant species. Given that an 
ePPND study will be conducted later in development, this protocol that allows enrollment of 
WOCBP has requirements for pregnancy testing (WOCBP only) and use of contraceptives to 
mitigate unintended exposures.
There is a theoretical risk that alterations in bone may occur based on published observations 
of osteopenia in mice genetically deficient in IFNβ.4 The potential for bone effects was 
assessed in the 3-month GLP toxicity study in sexually mature cynomolgus monkeys, and 
there were no microscopic findings in bone, nor alterations in circulating bone-related 
biomarkers. However, the potential for bone effects in developing/growing bones has not 


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been specifically assessed in growing animals. This risk is considered to be low given the 
lack of observed effects in the GLP toxicity study as well as the limited duration of total 
exposure to PF-06823859 in this study. While appropriate risk mitigation has been employed,
possible risks will be communicated to study participants in the ICD.
There is a potential risk of increased susceptibility to viral infections with IFNβ blockade as 
with any antagonist of Type 1 interferon signaling (eg, anti-IFNAR1, anti-IFNα, JAK 
inhibitors). Viral monitoring will be conducted as a precautionary measure to ensure 
participant safety. Furthermore, during the pandemic, study participants could be infected 
with the SARS-CoV-2 during study participation. This could lead to increased health risk for 
this participant and others in the study. Thus, participants must undergo COVID-19 specific 
assessments according to the SoA.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of PF-06823859 may be found in the IB, which is the SRSD for this 
study.
3. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 

To evaluate the safety and tolerability of single 
IV dose of 300 and 900 mg PF-06823859 in 
Japanese healthy participants.

Assessments of AEs/SAEs including IRR, 
infusion sites and viral infections, vital signs, 
ECGs and laboratory tests.
Secondary: 
Secondary: 

To evaluate the PK profile of single IV dose of 
300 and 900 mg PF-06823859 in Japanese 
healthy participants.

To evaluate the immunogenicity of 
PF-06823859.

Serum PF-06823859 PK parameters, as 
permitted by data: Cmax, Cmax (dn), Tmax, AUCinf,
AUCinf (dn), AUClast, AUClast (dn), AUC14day, 
AUC28day, t½, CL, Vss and MRT

Incidence of the development of ADA and NAb.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study to 
evaluate the safety, tolerability, immunogenicity and PK of PF-06823859 in Japanese healthy 
adult participants.
Approximately 12 participants are planned to be enrolled into the study. The study consists 
of 2 cohorts, and approximately 5 participants will be randomized to PF-06823859 and 
approximately 1 participant will be randomized to placebo in each cohort. Participants who 
discontinue prior to completion of the study for non-safety related reasons may be replaced at 


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the discretion of the investigator upon consultation with the sponsor. Each participant will 
receive PF-06823859 or placebo per the scheme summarized in Table 1.
Table 1.
Randomization Scheme
Cohort
Treatment
Number of participants
1
PF-06823859 300 mg
5
Placebo
1
2
PF-06823859 900 mg
5
Placebo
1
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single IV infusion of PF-06823859 or placebo. The 
participants in Cohort 2 should be dosed following at least 96 hours safety pause after the 
participants in Cohort 1 has been dosed. Participants will be admitted into the CRU 
approximately 1 day prior to dosing and are required to stay overnight in the CRU through 
completion of Day 5 evaluations. Participants will return to the CRU for outpatient follow-up 
visits per SoA through Day 157. Participants may be asked to return for additional follow-up 
visits beyond the anticipated end of study visit for safety reasons and/or at the discretion of 
the investigator.
ADA levels will be monitored from samples collected at the times specified in the SoA. 
Samples found to be positive will be further evaluated for NAb. Participants with positive 
results may be requested to return for additional follow-up for up to approximately 3 months 
after the last scheduled follow-up visit.
4.2. Scientific Rationale for Study Design
The purpose of this study is to evaluate the safety, tolerability, immunogenicity and PK of 
PF-06823859 after single IV administration to Japanese healthy adult participants. This study 
will be randomized, placebo-controlled, double-blinded to treatment assignment in each 
cohort to permit an unbiased assessment of safety and tolerability.
To date, no safety, immunogenicity and PK data of PF-06823859 in Japanese are available. 
Although there is no expected relevant PK difference between Japanese and Westerners 
because monoclonal antibodies are generally known that the absence of ethnic differences in 
their distribution and elimination, similar to that of endogenous IgG,5 it is still important to 
evaluate safety and characterize PK in Japanese participants before initiating studies in the 
targeted Japanese patient population.
Single-dose rather than repeated dosing is planned in the study as the steady-state PK can be 
well predicted from single-dose data. The study duration and frequency of each assessment 
were decided based on information of Study C0251001.


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Assessment of clinical safety laboratory tests (Appendix 2), vital signs, 12-lead ECG, 
physical examinations, and AE monitoring will provide essential data to evaluate the safety 
and tolerability of PF-06823859. There is a potential risk of increased susceptibility to viral 
infections with IFNβ blockade as with any antagonist of Type 1 interferon signaling (eg, 
anti-IFNAR1, anti-IFNα, JAK inhibitors). Viral monitoring will be conducted as a 
precautionary measure to ensure participant safety.
COVID-19 specific assessments have been incorporated to minimize the risks of COVID-19 
related complications to participants and the study site personnel.
4.2.1. Choice of Contraception/Barrier Requirements
Human reproductive safety data are not available for PF-06823859, but there is no suspicion 
of human teratogenicity based on the intended pharmacology of the compound. Therefore, 
the use of a highly effective method of contraception is required (see Appendix 4).
4.2.2. Collection of Retained Research Samples
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
The proposed single IV dose levels are 300 mg and 900 mg. These doses are selected based 
on the safety and tolerability in Study C0251001,
 
PF-06823859 doses of 300 mg and 900 mg have been selected to evaluate the safety, 
tolerability, immunogenicity and PK of PF-06823859 in Japanese healthy adult participants 
so that safety and tolerability can be examined in the dose range including the maximum 
potential dose in the planned global late phase studies.
 
 
As described in Section 2.2.2, PF-06823859 repeated IV dose of 600 mg IV Q4W for a total 
of 2 doses was generally safe and well tolerated in non-Japanese healthy participants in 
Study C0251001. In addition, Rac (based on AUCτ) and Rac, Cmax (based on Cmax) following 
600 mg IV Q4W dosing on Day 29 were 1.4 and 1.3, respectively. Considering these results 
from Study C0251001, exposure following a single 900 mg IV dose is expected to be 
comparable to steady-state exposure following repeated IV dose of 600 mg IV Q4W.
Based on the above, 300 mg and 900 mg, which 
 
allow the direct comparison of PK with Cohort 3 (300 mg
single IV dose) and Cohort 4 (900 mg single IV dose) in Study C0251001 respectively, has 
been selected as the proposed dose level in the current study.
CCI
CCI
CCI


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4.4. 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.
A participant is considered to have completed the study if he/she has completed all periods of 
the study, including the last visit.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male and female participants must be 20 to 55 years of age, inclusive, at the time of 
signing the ICD.

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants must have 4 biologically Japanese grandparents born in Japan.
3. Male and female participants who are overtly healthy as determined by medical 
evaluation including medical history, physical examination, laboratory tests, and 
12-lead ECG.
4. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
5. BMI of 17.5 to 25 kg/m2; and a total body weight >50 kg (110 lb).


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Informed Consent:
6. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine, 
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or 
allergic disease (including drug allergies, but excluding untreated, asymptomatic, 
seasonal allergies at the time of dosing).
2. History of HIV infection, hepatitis C or syphilis; positive testing for HIV, HCVAb or 
syphilis at screening.
3. Infection with HBV as defined in Section 8.2.6.1.
4. Clinically significant abnormality, including but not limited to current, active TB or 
previous inactive TB, general infections, heart failure or malignancy, on chest X-ray 
performed at screening or within 12 weeks of screening.
5. History of autoimmune disorders.
6. History of allergic or anaphylactic reaction to a therapeutic drug or any components 
in the study intervention.
7. Participants with clinically significant infections, based on which the investigator
judges that the participant should not be enrolled in the study, within 28 days prior to 
the screening visit.
8. Participants with a fever, based on which the investigator judges that the participant 
should not be enrolled in the study, within the last 7 days prior to dosing.
9. Participants who have evidence of TB infection as defined in Section 8.2.7.

Participants who have been treated or are currently being treated for active or 
latent TB infection are to be excluded.

Participants with a history of either untreated or inadequately treated latent or 
active TB infection are to be excluded.


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10. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality or other conditions or 
situations related to COVID-19 pandemic (eg, Contact with positive case, residence, 
or travel to an area with high incidence) that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for 
the study.
Prior/Concomitant Therapy:
11. Use of prescription or nonprescription drugs and dietary and herbal supplements 
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention.  (Refer to Section 6.8 for additional details).
12. Recent exposure to any live or attenuated live virus vaccines within 6 weeks of 
admission to CRU.

The use of COVID-19 vaccines (except for live or attenuated live virus vaccines)
are allowed before 14 days prior to Day 1 or after discharge from CRU.
Prior/Concurrent Clinical Study Experience:
13. Participants who have received PF-06823859 or any other IFNor IFNtherapy at 
any time in the past.
14. Previous administration with an investigational drug within 4 months (180 days for 
biologics) or 5 half-lives preceding the first dose of study intervention used in this 
study (whichever is longer).
Diagnostic Assessments:
15. A positive urine drug test.
16. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at 
least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg 
(diastolic), the BP should be repeated 2 more times and the average of the 3 BP 
values should be used to determine the participant’s eligibility.
17. Screening PR >100 bpm. If the PR is greater than 100 bpm, the PR should be 
repeated 2 more times and the average of the 3 PR values should be used to determine 
the participant’s eligibility.
18. Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities that 
may affect participant safety or interpretation of study results (eg, baseline QTc 
interval >450 msec, complete LBBB, signs of an acute or indeterminate-age 
myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, 
second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). 


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If the baseline uncorrected QT interval is >450 msec, this interval should be 
rate-corrected using the Fridericia method and the resulting QTcF should be used for 
decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, 
the ECG should be repeated 2 more times and the average of the 3 QTc or QRS 
values should be used to determine the participant’s eligibility. Computer-interpreted 
ECGs should be overread by a physician experienced in reading ECGs before 
excluding a participant.
19. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat test, if deemed necessary:

AST or ALT level ≥1.5 × ULN;

Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's 
syndrome may have direct bilirubin measured and would be eligible for this study 
provided the direct bilirubin level is ≤ULN.
20. A positive COVID-19 test by PCR at screening.
Other Exclusions:
21. History of alcohol abuse or binge drinking and/or any other illicit drug use or 
dependence within 6 months of screening. Binge drinking is defined as a pattern of 
5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, 
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 
1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
22. Blood donation (excluding plasma donations) of approximately ≥400 mL within 3 
months or ≥200 mL within a month prior to dosing. Additionally, approximately 
≥400 mL within 4 months for female participants.
23. History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin 
is planned to flush intravenous catheters.
24. History of substance abuse within 12 months of the screening visit.
25. Pregnant females; breastfeeding females.
26. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
27. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members.


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5.3. Lifestyle Considerations
The following guidelines are provided:
5.3.1. Meals and Dietary Restrictions

Participants must abstain from all food and drink (except water) at least 4 hours prior 
to any safety laboratory evaluations.

While participants are confined, their total daily nutritional composition should be 
approximately 55% carbohydrate, 30% fat, and 15% protein. The daily caloric intake 
per participant should not exceed approximately 3200 kcal.
5.3.2. Caffeine, Alcohol, and Tobacco

Participants will abstain from caffeine-containing products for 24 hours prior to the 
start of dosing in the CRU and during clinical confinement at the CRU.

Participants will abstain from alcohol for 24 hours prior to admission to the CRU and 
continue abstaining from alcohol during clinical confinement at the CRU. Participants 
may undergo an alcohol breath test or blood alcohol test at the discretion of the 
investigator.

Participants will abstain from the use of tobacco- or nicotine-containing products for 
24 hours prior to dosing and during clinical confinement at the CRU.
5.3.3. Activity

Participants will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests. Walking at a normal pace will be permitted.
5.3.4. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use acceptable effective contraception consistently 
and correctly and document the conversation and the participant’s affirmation in the 
participant’s chart (participants need to affirm their consistent and correct use of at least 1 of 
the selected methods of contraception) considering that their risk for pregnancy may have 
changed since the last visit. In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.


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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study. Screen 
failure data are collected and remain as source and are not reported on the CRF.
Individuals who do not meet the criteria for participation in this study (screen failure) may 
not be rescreened.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
For the purposes of this protocol, study intervention refers to PF-06823859 and placebo.
6.1. Study Intervention(s) Administered
PF-06823859 100 mg/mL Solution for Injection will be supplied by Pfizer and packaged in a 
single-use carton containing a 6 mL glass vial sealed with a stopper and aluminum flip off 
cap. Each vial contains PF-06823859 in 1.35 mL of solution. Placebo for PF-06823859 100 
mg/mL Solution for Injection will also be provided.
These products will be supplied to the CRU as open label packaged supplies and must be 
received at the site by unblinded site staff. The site will take all necessary precautions to 
maintain the investigator and site personnel blind.
6.1.1. Administration
Intervention Name
PF-06823859 100 mg/mL
Placebo for PF-06823859
ARM Name
(group of patients receiving a 
specific treatment, or no treatment)
Active
Placebo
Type
Biologic
Biologic
Dose Formulation
Solution for injection
Solution for injection
Unit Dose Strength(s)
100 mg/mL
0 mg/mL
Dosage Level(s)
300 mg, 900 mg
Placebo
Route of Administration
Intravenous
Intravenous
Use
Experimental
Placebo
IMP or NIMP
IMP
IMP
Sourcing
Provided by the sponsor.
Provided by the sponsor.
Packaging and Labeling
Study intervention will be provided 
in vials packaged in individual 
cartons. Each vial and carton will be 
labeled as required per country 
requirement.
Study intervention will be provided 
in vials packaged in individual 
cartons. Each vial and carton will 
be labeled as required per country 
requirement.
Participants will receive study intervention at approximately 0800 hours on Day 1 (plus or 


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minus 4 hours). Study intervention does not require fasting, but it should be noted that the 
safety laboratory tests at Day -1 prior to the dose of study intervention need a fast of at least 
4 hours. Investigator site personnel will administer study intervention as a 60-minute IV
using a calibrated infusion pump. Study medication must not be administered as an IV push 
or bolus. The infusion rate, amount of volume infused, start and stop time of the infusion will 
be recorded. Time 0 is the time when the study intervention infusion begins. The infusion 
will be on the opposite arm from PK sampling.
Administer study intervention according to the IP Manual.
6.1.1.1. Intravenous Infusion Discontinuation

If a participant experiences symptoms typical of an allergic reaction, the study 
intervention infusion should be discontinued immediately and permanently.

If a participant experiences symptoms typical of IRR (eg, lightheadedness, nausea, 
chills, fever), the study intervention infusion should be stopped. At the discretion of 
the investigator, the infusion can be restarted at a slower rate if symptoms are 
resolved within 1 hour after the stop of infusion. If symptoms return, then the study 
intervention infusion should be discontinued immediately and permanently.

In the event that there is an infusion interruption, the entire duration of study 
intervention infusion, from the initial start of infusion to the completion of infusion, 
should not exceed 3 hours. Participants will receive appropriate treatment at the 
discretion of the investigator.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 


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to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. See the IP manual for storage conditions of the study intervention.
7. The head of the medical institution (where applicable) or study intervention 
administrator is responsible for study intervention accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records), such as 
the IPAL or sponsor-approved equivalent. All study interventions will be accounted 
for using a study intervention accountability form/record.
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the study intervention ready for administration or dispensing to the participant by qualified 
staff. Dispensing is defined as the provision of study intervention, concomitant treatments, 
and accompanying information by qualified staff member(s) to a healthcare provider, 
participant in accordance with this protocol. Local health authority regulations or investigator 
site guidelines may use alternative terms for these activities.
PF-06823859 and placebo will be prepared by qualified unblinded site personnel according 
to the IP manual. Blinded study intervention will be administered in a blinded fashion to the 
participant.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Participants will be randomly assigned to receive study intervention from a central 
randomization scheme. Investigators will remain blinded to each participant’s assigned study 
intervention throughout the course of the study. In order to maintain this blind, an otherwise 


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uninvolved third party (for example, pharmacist) will be responsible for the preparation and 
dispensing of all study intervention according to the randomization schedule and assigned 
treatment for the individual participant.
6.3.2. Breaking the Blind
The method for breaking the blind in this study will be manual. A sealed envelope that 
contains the study intervention assignment(s) for each participant will be provided to the 
investigator. The sealed envelope will be retained by the investigator (or representative) in a 
secured area. In case of an emergency, the investigator has the sole responsibility for 
determining if unblinding of a participant’s treatment assignment is warranted. Participant 
safety must always be the first consideration in making such a determination. If the 
investigator decides that unblinding is warranted, the investigator should make every effort to 
contact the sponsor prior to unblinding a participant’s treatment assignment unless this could 
delay further management of the participant. If a participant’s treatment assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. When the 
blinding code is broken, the reason must be fully documented and entered on the CRF.
Once the study is complete, all envelopes (sealed and opened) must be inventoried and 
retained until authorization for destruction has been provided.
Blood specimens will be obtained from all participants for PK analysis to maintain the study 
blind at the investigator site. Only the investigator site staff and blinded study monitor, if 
assigned, will be blinded to study treatment. Other Pfizer personnel will be unblinded to
participant treatments in order to permit real-time interpretation of the safety and PK data. 
The blinded study monitor, if assigned, will remain blinded to treatment until all monitoring 
for the study has been completed. Specimens from participants randomized to placebo will 
not be routinely analyzed. To minimize the potential for bias, treatment randomization 
information will be kept confidential by Pfizer unblinded personnel and will not be released 
to the blinded investigator or blinded investigator site personnel until the study database has 
been locked or the investigator requests unblinding for safety reasons.
6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of dose administered 
in the clinic will be recorded in the source documents and recorded in the CRF. The dose of 
study intervention and study participant identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study intervention.
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. Dose Modification
Not applicable.
6.6. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation.
6.7. Treatment of Overdose
For this study, any dose of PF-06823859 greater than 2000 mg within a month will be 
considered an overdose.
There is no 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-06823859 (whichever 
is longer).
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 1 day from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis).
6.8. Concomitant Therapy
Use of prescription or nonprescription drugs and dietary and herbal supplements are 
prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study 
intervention. Limited use of nonprescription medications that are not believed to affect 
participant safety or the overall results of the study may be permitted on a case-by-case basis 
following approval by the sponsor. Acetaminophen/paracetamol may be used at doses of 
≤1 g/day. Ibuprofen may be used at doses of 1.6 g/day.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
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.


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Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments.
6.8.1. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with PF-06823859; standard medical 
supportive care must be provided to manage the AEs. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
Since this is a single-dose study, this section is not applicable.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study. Participants should be questioned regarding 
their reason for withdrawal.  
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.


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7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
7.3. Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.


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Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Participants will be screened within 28 days prior to administration of the study intervention 
to confirm that they meet the study population criteria for the study. If the time between 
screening and dosing exceeds 28 days as a result of unexpected delays (eg, delayed drug 
shipment), then participants do not require rescreening if the laboratory results obtained prior 
to first dose administration meet eligibility criteria.
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.
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 
(PR and BP) should be collected prior to the insertion of the catheter.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study is approximately 
290 mL. The actual collection times of blood sampling may change. Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 56 consecutive 
days.


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To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol.
8.1. Efficacy Assessments
Not applicable.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A physical examination will include, at a minimum, head, ears, eyes, nose, mouth, skin, heart 
and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological 
systems. 
Physical examinations may be conducted by a physician. 
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. 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to 8.3.3.
8.2.2. Chest X-ray
Chest radiograph (posterior-anterior and lateral views are recommended, however, local 
guidelines should be followed) or other appropriate diagnostic image (ie, CT or MRI) should 
be taken at screening visit or within 12 weeks prior to screening visit and read by a qualified 
radiologist and must show no evidence of abnormalities including but not limited to current, 
active TB or previous inactive TB, general infections, heart failure or malignancy.
Documentation of the official reading must be located and available in the source 
documentation.
8.2.3. Vital Signs
Supine BP will be measured with the participant’s arm supported at the level of the heart, and 
recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study. BP should not be taken 


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from the arm with an IV 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 PR is acceptable; however, when done 
manually, PR 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 PR should be 
obtained prior to the nominal time of the blood collection.
Additional collection times, or changes to collection times, of BP and PR will be permitted, 
as necessary, to ensure appropriate collection of safety data.
8.2.3.1. Temperature
Temperature (oral or axillary) will be measured. No eating, drinking, or smoking is allowed 
for 15 minutes prior to the measurement.
8.2.4. Electrocardiograms
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 HR and measures PR, QT, and QTc intervals and QRS complex.
Alternative lead placement methodology using torso leads (eg, Mason-Likar) should not be 
used 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. 
To ensure safety of the participants, a qualified individual at the investigator site will make 
comparisons to baseline measurements. Additional ECG monitoring will occur if a) a 
postdose QTc interval is increased by ≥45 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 2 additional ECGs will be collected approximately 2 to 4 minutes apart to 
confirm the original measurement. If the QTc values from these repeated ECGs remain above 
the threshold value, then a single ECG must be repeated at least hourly until QTc values from 
2 successive ECGs fall below the threshold value that triggered the repeat measurement.
If a) a postdose QTc interval remains 45 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 criteria 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 provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.5. Infusion Site Assessment
Participants should be monitored from start of study intervention infusion until the end of 
infusion to assess the infusion sites. The infusion sites will be assessed for erythema, 
induration, ecchymosis, pain, and pruritus, or other observed characteristics after study 
intervention.
Any observed abnormality at the infusion site should be treated according to the 
investigator’s standard of care and reported as AEs.
8.2.6. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 150 calendar days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
Participants may undergo random urine drug testing at the discretion of the investigator.  
Drug testing conducted prior to dosing must be negative for participants to receive study 
intervention. 
8.2.6.1. HBV testing
Participant’s eligibility should be determined according to the following criteria based on the 
results of positive testing for HBsAg, HBcAb and HBsAb at screening.


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
If all 3 tests are negative, the participant is eligible for study inclusion.

If HBsAg is positive, the participant must be excluded from participation in the 
study.

If HBsAg is negative, HBcAb is positive, and HBsAb is negative, the participant 
must be excluded from participation in the study.

If HBsAg is negative, HBcAb is negative, HBsAb is positive, and prior HBV 
vaccination is unequivocally documented, the participant is eligible for the study and 
does not require HBV DNA monitoring during the study.

If HBsAg is negative, HBcAb is negative, HBsAb is positive, and no unequivocal 
documentation of prior HBV vaccination is available, the participant is required to 
undergo HBV DNA reflex testing. If HBV DNA is detected, the participant must be 
excluded from participation in the study; If HBV DNA is undetectable, the 
participant is eligible for study inclusion but required to HBV DNA testing for the 
subsequent visits according to the SoA.

If HBsAg is negative, HBcAb is positive, and HBsAb is positive, the participant is 
required to undergo HBV DNA reflex testing. If HBV DNA is detected, the 
participant must be excluded from participation in the study; If HBV DNA is 
undetectable, the participant is eligible for study inclusion but required to HBV
DNA testing for the subsequent visits according to the SoA.
A participant who tested viral load positive for HBV at any time during the study should 
consider starting nucleoside antagonist immediately in parallel with consultation with 
hepatologist in accordance with the Japan Society of Hepatology Guidelines for the 
management of HBV infection.6
8.2.7. Tuberculosis test
Participants should be screened for TB using an IGRA. IGRA will be tested during screening 
or within 12 weeks prior to Day 1. The following are acceptable assays: QuantiFERON®-TB 
Gold In Tube (QFT-G) test and T-spot®TB (T-Spot) test. If at any time the participant has 
signs or symptoms associated with TB, additional TB testing will be performed.
Participant’s eligibility should be determined according to the following criteria based on the 
results of IGRA during screening or within 12 weeks prior to Day 1.

Participants who test negative for IGRA is eligible for study inclusion.

Participants who test positive for IGRA must be excluded from participation in the 
study.


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
If the results of the IGRA are indeterminate, the test may be repeated, and if a 
negative result is obtained, enrollment may proceed. A positive test on repeat is 
exclusionary. Participants with repeat indeterminate IGRA results may be enrolled 
after consultation with an infectious disease and/or pulmonary specialist who 
determines that the risk of infection is low (ie, participant would be acceptable for 
immunosuppressant treatment without additional action).
Site personnel should follow the processing and analyses steps based on the assay chosen.  
Ensure incubation steps are followed as appropriate. Documentation of IGRA product used 
and the test result must be in the participant’s source documentation.
8.2.8. Viral Surveillance
Blood samples for possible analysis of CMV, EBV, HSV-1, HSV-2, VZV and HHV6 will be 
collected according to the times outlined in the SoA.
Note: Due to long turnaround time, the retrospective nature of these labs might make their 
reporting time quite delayed.
In addition to time points specified in the SoA, a blood sample for viral surveillance sample 
may also be taken at the time of an AE, as clinically appropriate.
8.2.9. COVID-19 Specific Assessments
Participants will be tested for SARS-CoV-2 infection by PCR at the timepoints specified in 
the SoA, or if they develop COVID-19 like symptoms. Additional testing may be required by 
local regulations or by the Principal Investigator. The test result must be negative in order for 
a participant to proceed with admission on Day -1. COVID-19 tests may be conducted at 
central or local labs. COVID-19 specific assessments data will be considered source data. If 
the participant has a positive COVID-19 test result, the concerned participant may be isolated 
and withdrawn from the study at the discretion of the investigator upon consultation with the 
sponsor. The positive COVID-19 test result should be recorded in the AE section of the CRF.
8.2.10. 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 the study intervention. 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.


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8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study (see Section 7.1). 
During the active collection period as described in Section 8.3.1, 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.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 150 calendar days, except as indicated below, after the last administration of the 
study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator.
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 permanently discontinues or temporarily discontinues study 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 information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 


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considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4.
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 or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.


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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 toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure, occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

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 EDP:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact.


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
A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion 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 
pregnancy will be collected after the start of study intervention and until 150 calendar 
days.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual 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. 


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Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if:

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.

A female 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 ingestion 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.
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 
study intervention, which may or may not lead to the occurrence of an AE.
The investigator must report any instance of 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 about the occupational exposure 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 must be maintained in the 
investigator site file.


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8.3.6. Cardiovascular and Death Events
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable.
8.3.8. Adverse Events of Special Interest
Not applicable.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy is not expected in the study population.
8.3.9. Medical Device Deficiencies
Not applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.


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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Pharmacokinetics 
Blood samples of approximately 3 mL, to provide approximately 1 mL serum, will be 
collected for measurement of serum concentrations of PF-06823859 as specified in the SoA. 
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor. The actual date and time (24-hour clock time) of each 
sample will be recorded.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. Collection of samples more than 10 hours after dose
administration and during confinement in the CRU 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 the CRF. During follow-up 
period (after Day 5), collection of samples that are obtained within 3 days of planned visit
will not be captured as a protocol deviation, as long as the exact time of the collection is 
noted on the source document and the CRF.
Samples will be used to evaluate the PK of PF-06823859. Samples collected for analyses of 
PF-06823859 serum concentration may also be used to evaluate safety or efficacy aspects 
related to concerns arising during or after the study, for metabolite identification and/or 
evaluation of the bioanalytical method, 
Genetic analyses will not be performed on these serum samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
Samples collected for measurement of serum concentrations of PF-06823859 will be 
analyzed using a validated analytical method in compliance with applicable SOPs. Potential 
metabolites may be analyzed with either validated or exploratory methods.
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.  
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On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
Drug concentration information that would unblind the study will not be reported to 
investigator sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.7. Immunogenicity Assessments
Blood samples of approximately 6 mL, to provide approximately 2 mL serum, will be 
collected for determination of ADA and NAb as specified in the SoA. Instructions for the 
collection and handling of biological samples will be provided in the laboratory manual or by 
the sponsor. The actual date and time (24-hour clock time) of each sample will be recorded.
Samples collected for determination of ADA and NAb may also be used for additional 
characterization of the immune response and/or evaluation of the bioanalytical method, 
 
 
Genetic analyses will not be performed on these serum samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
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Samples will be analyzed using a validated analytical method in compliance with applicable 
SOPs. Samples tested as ADA positive (not just confirmed positive, but also with a titer 
positive result) will be further tested for NAb using validated NAb assays.
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (eg, sample collection and processing steps, 
interim storage, or shipping conditions), including any actions taken, must be documented 
and reported to the sponsor. On a case-by-case basis, the sponsor may make a determination 
as to whether sample integrity has been compromised.
Immunogenicity information that would unblind the study will not be reported to investigator 
sites or blinded personnel until the study has been unblinded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Statistical Hypotheses
No statistical hypotheses will be tested in this study.
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:


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Participant Analysis 
Set
Description
Enrolled/Randomly 
assigned to study 
intervention
"Enrolled" means a participant's, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process.  
Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless otherwise 
specified by the protocol. A participant will be considered 
enrolled if the informed consent is not withdrawn prior to 
participating in any study activity after screening.
Safety Analysis Set
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Participants 
will be analyzed according to the product they actually 
received.
PK concentration
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention and in whom at 
least 1 serum sample concentration value of PF-06823859 is 
reported.
PK parameter
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention and who have at 
least 1 of the PK parameters of PF-06823859 of interest 
calculated.
Immunogenicity
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention with at least one 
post-treatment anti-drug (PF-06823859) antibody 
determination.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.3.1. General Considerations
All analyses described below will be conducted by treatment. In addition, data from placebo 
in Cohort 1 and Cohort 2 will be pooled.
9.3.2. Primary Endpoint(s)
All safety analyses will be performed on the safety analysis set
The primary endpoints of this study are assessments of AEs/SAEs including IRR, viral 
infections, vital signs, ECGs and laboratory tests.


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The primary endpoints will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and/or graphical presentations in 
order to evaluate the safety and tolerability of PF-06823859.
9.3.2.1. Electrocardiogram (ECG) Analysis
Changes from baseline for the ECG parameters (QT interval, HR, QTc interval, PR interval, 
and QRS interval) will be summarized by treatment and time.
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of 
Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with corrected and uncorrected QT values 500 msec 
will be summarized.
9.3.3. Secondary Endpoint(s)
9.3.3.1. Pharmacokinetic Analyses
PK parameters for PF-06823859 following single-dose administration will be derived from 
the serum concentration-time profiles using noncompartmental methods, as data permit.
The PK parameters to be assessed in this study, their definition, and method of determination 
are listed in analysis as described in Table 2. Actual PK sampling times will be used in the 
derivation of PK parameters.
The serum PK parameters in Table 2 will be summarized descriptively by treatment group in 
accordance with Pfizer data standards, as data permit. The plot will include individual 
participant values and the geometric means for each dose. These plots will be used to help 
understand the relationship between the PK parameters and dose.


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Table 2.
Serum PF-06823859 PK Parameters
Parameter
Definition
Method of Determination
AUC14day
Area under the serum concentration-time 
profile from time 0 to 14 days post-dose
(336 hours)
Linear/Log trapezoidal method
AUC28day
Area under the serum concentration-time 
profile from time 0 to 28 days post-dose
(672 hours)
Linear/Log trapezoidal method
AUClast
Area under the serum concentration-time 
profile from time 0 to the time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUClast (dn)
Dose normalized AUClast
AUClast/Dose
AUCinfa
Area under the serum concentration-time 
profile from time 0 extrapolated to 
infinite time
AUClast + (Clast*/kel),
where Clast* is the predicted serum 
concentration at the last quantifiable time 
point estimated from the log-linear 
regression analysis
AUCinf (dn)
Dose normalized AUCinf
AUCinf/Dose
Cmax
Maximum serum concentration
Observed directly from data
Cmax (dn)
Dose normalized Cmax
Cmax/Dose
Tmax
Time at which Cmax occurs
Observed directly from data as time of first 
occurrence
t1/2 a
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  
CL a
Clearance 
Dose/AUCinf
Vss a
Volume of distribution at steady state
CL*MRT
MRT
Mean residence time 
AUMCinf/AUCinf – DOF/2, where AUMCinf
is the area under the moment curve from 
time 0 extrapolated to infinity and DOF is 
the duration of the IV infusion.
a. If data permitted. 
9.3.3.2. Immunogenicity Analyses
Overall incidence of development of ADA, NAb will be calculated and summarized by 
treatment and time points specified in the SoA. Participants level immune response will also 
be summarized by treatment. Effect of positive ADA and neutralizing immune response on 
safety and PK may be assessed, if appropriate.
9.3.4. Other Safety Analyses
AEs, ECGs, BP, PR 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 PR 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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Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted. However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE.  
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted. Demographic data collected at screening will be reported.
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is a sponsor-open
study, the sponsor may conduct unblinded reviews of the data during the course of the study 
for the purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical 
development.
9.5. Sample Size Determination
A sufficient number of participants will be screened to achieve 6 participants randomly 
assigned to study intervention per cohort and 12 evaluable participants for an estimated total 
of 5 evaluable participants in PF-06823859 300 mg, 5 evaluable participants in PF-06823859 
900 mg, or 2 evaluable participants in placebo. Approximately 12 participants will be 
randomly assigned to study intervention such that approximately 12 evaluable participants 
complete the study.
A total sample size of 12 participants (including 10 active and 2 placebo) is not based on any 
statistical considerations. The sample size was based on the clinical consideration to provide 
safety and tolerability information and pharmacological considerations and on the need to 
minimize exposure to healthy participants. No formal inferential statistics will be applied to 
the safety or PK data.
Participants who discontinue prior to completion of the study for non-safety related reasons
may be replaced at the discretion of the investigator upon consultation with the sponsor. 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the head of the medical institution, 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.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (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 


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information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines 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, including the 
risks and benefits, to the participant and answer all questions regarding the study. The 
participant should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection 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 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant 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 on which 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.


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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 will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.4. Committees Structure
10.1.4.1. Data Monitoring Committee 
This study will not use a DMC.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.


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EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.


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The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study critical data items and 
processes (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, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator or authorized site personnel for 15 years after study 
completion unless local regulations or institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without written 
notification to the sponsor. The investigator or authorized site personnel 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 or authorized site personnel will 
ensure that all copies of such data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.


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Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data and its origin can be found in the study monitoring 
plan, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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 guidelines, and all applicable regulatory requirements.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.


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If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications,
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer-intervention 
related information necessary for the appropriate scientific presentation or understanding of 
the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation .
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 


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the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Table 3.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils (%)
Eosinophils (%)
Monocytes (%)
Basophils (%)
Lymphocytes (%)
BUN and creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Chloride
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
At screening only:

FSHb

HIV

HBsAg

HBsAb

HBcAb

HCVAb

Syphilis

IGRAc
As per SoA:

Urine drug screeningd

Pregnancy test 
(-hCG)e

Viral surveillance: 
CMV, VZV, EBV,
HHV6, HSV-1, HSV-2

PT

INR

aPTT

HBV DNAf, if 
applicable

COVID-19 testing
a.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
b.
For confirmation of postmenopausal status only.
c.
IGRA will be performed according to Section 8.2.7.
d.
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, 
benzodiazepines, and amphetamines (others are site and study specific).
e.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/EC. Serum or urine -hCG for female participants of childbearing potential.
f.
HBV DNA testing will be performed according to Section 8.2.6.1.
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.


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or 
not considered related to the study intervention.

Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Any 
abnormal laboratory test results that meet any of the conditions below must be 
recorded as an AE:

Is associated with accompanying symptoms;

Requires additional diagnostic testing or medical/surgical intervention;

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition, including either 
an increase in frequency and/or intensity of the condition.

New condition 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 or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.


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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms 
of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
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 admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.


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d. Results in persistent or significant 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), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a 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 participant 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.
g. Other situations:

Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations, such as 
significant medical events that 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.
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 


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nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must 
be completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Note:  Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF.
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE). **
Environmental or 
occupational exposure 
to the product under 
study to a non-
participant (not 
involving EDP or EDB).
None.  Exposure to a study 
non-participant is not 
collected on the CRF.
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.***
*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to 
Pfizer Safety using CT SAE Report Form and EDP Supplemental Form; if the EDP is 
associated with an SAE, then the SAE is reported to Pfizer Safety using the CT SAE Report 
Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form which would also include 
details of any SAE that might be associated with the EDB. 
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational exposure 
are reported to Pfizer Safety using the CT SAE Report Form. 

When an AE or 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.


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
The investigator will then record all relevant AE or SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or 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 or 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: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc.

Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self care ADL. Self care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship.

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.


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
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 or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or 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 study intervention caused the 
event, then the event will be handled as “related to study intervention” for 
reporting purposes, as defined by the sponsor. In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator 
must record this causal relationship in the source documents and CRF, and report 
such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations, as medically indicated or as 
requested by the sponsor, to elucidate the nature and/or causality of the AE or 
SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other 
healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.


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
New or updated information will be recorded in the originally submitted 
documents.

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) 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 and Barrier Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 150 calendar days after the last dose of study 
intervention, which corresponds to the time needed to eliminate reproductive safety risk of 
the study intervention(s):

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 contraception/barrier as detailed below:

Agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception as a condom may 
break or leak when having sexual intercourse with a woman of childbearing 
potential who is not currently pregnant.
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), preferably with low user dependency, as described below 
during the intervention period and for at least 150 calendar days after the last dose of 
study intervention, which corresponds to the time needed to eliminate any 
reproductive safety risk of the study intervention(s). The investigator should evaluate 
the effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with high user dependency, as described below during the 
intervention period and for at least 150 calendar days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention(s). In addition, a second effective method of 


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contraception, as described below, must 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.
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. 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 participant’s medical records, medical examination, or 
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female.

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition:

A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years old and not using hormonal 
contraception or HRT. 

A female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 


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if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
Highly Effective Methods That Have Low User Dependency
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.*
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion (eg, bilateral tubal ligation).
5. Vasectomized partner.

A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP 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.
Highly Effective Methods That Are User Dependent
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation.

Oral;

Intravaginal;*

Transdermal;*

Injectable.*
7. Progestogen-only hormone contraception associated with inhibition of ovulation.

Oral;*

Injectable.*
8. Sexual abstinence.


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
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*;

A combination of male condom with either cervical cap*, diaphragm*, or sponge 
with spermicide* (double-barrier methods).
*) Not approved in Japan


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CCI


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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 DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within 
the same laboratory sample). In rare instances, by the time TBili elevations are detected, 
AST/ALT values might have decreased. This occurrence is still regarded as a potential DILI.  
Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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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 Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or 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, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by 60 msec from 
baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’
duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia.

Asystole:

In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an 
escape rhythm that is below the AV node. 

In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).


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
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm 
(heart rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to
<100 bpm), and monomorphic/polymorphic ventricular tachycardia (HR 
>100 bpm (such as torsades de pointes)).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as SAEs

Change in pattern suggestive of new myocardial infarction.

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring 
cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
ADA
antidrug antibodies
ADL
activities of daily living
AE
adverse event
ALT
alanine aminotransferase
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC14day
AUC from time 0 to 14 days post-dose
AUC28day
AUC from time 0 to 28 days post-dose
AUCinf
AUC from time 0 extrapolated to infinite time
AUClast
AUC from time 0 to the time of the last quantifiable concentration
AUCτ
AUC from time 0 to time τ, the dosing interval
AV
atrioventricular
-hCG
beta-human chorionic gonadotropin
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
Cav
concentration average
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CL
clearance
Cmax
maximum observed concentration
CMV
cytomegalovirus
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSR
Clinical Study Report
CT
computed tomography
CT SAE
clinical trial serious adverse event (report form)
DILI
drug-induced liver injury
DM
dermatomyositis
DMC
Data Monitoring Committee
dn
dose normalized
DNA
deoxyribonucleic acid


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Abbreviation
Term
EBV
Epstein-Barr virus
EC
Ethics Committee
ECC
emergency contact card
ECG
electrocardiogram
eCRF
electronic case report form
EDB
exposure during breastfeeding
EDP
exposure during pregnancy
EMA
European Medicines Agency
ePPND
enhanced pre and postnatal development
ET
early termination
EU
European Union
EudraCT
European Union Drug Regulating Authorities Clinical Trials
(European Clinical Trials Database)
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLP
Good Laboratory Practice
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HBV
hepatitis B virus
HBV DNA
hepatitis B virus DNA
HCVAb
hepatitis C antibody
HHV6
human herpesvirus 6
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
HSV-1
herpes simplex virus type 1
HSV-2
herpes simplex virus type 2
IB
Investigator’s Brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN
interferon
IFNAR
Type 1 interferon /receptor
IgG
immunoglobulin G
IGRA
Interferon-Gamma Release Assays
IMP
investigational medicinal product
IND
Investigational New Drug 
INR
international normalized ratio
IP manual
investigational product manual


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Abbreviation
Term
IPAL
Investigational Product Accountability Log
IRB
Institutional Review Board
IRR
infusion related reaction
IV
intravenous(ly)
JAK
Janus kinase
kel
terminal phase rate constant
LBBB
left bundle branch block
LFT
liver function test
MAD
multiple ascending dose
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MRI
magnetic resonance imaging
MRT
mean residence time
msec
millisecond
N/A
not applicable
NAb
neutralizing antibodies
NIMP
noninvestigational medicinal product
PCR
polymerase chain reaction
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PR
pulse rate
PT
prothrombin time
PVC
premature ventricular contraction/complex
Q2W
once every 2 weeks
Q4W
once every 4 weeks
QFT-G
QuantiFERON®-TB Gold In Tube
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
Rac
accumulation ratio for AUCτ
Rac, Cmax
accumulation ratio for Cmax
RBC
red blood cell
SAD
single ascending dose
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous(ly)
SLE
systemic lupus erythematous
SoA
schedule of activities
CCI


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Abbreviation
Term
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBili
total bilirubin
TEAE
treatment emergent adverse event
t½
terminal phase half-life
THC
tetrahydrocannabinol
Tmax
time to reach Cmax
T-Spot
T-spot®TB
ULN
upper limit of normal
US
United States
Vss
volume at steady state
VZV
varicella-zoster virus
WBC
white blood cell
WOCBP
woman of childbearing potential


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11. REFERENCES
1.
National Organization for Rare Disorders, NORD 2015. Available from:
http://rarediseases.org/rare-diseases/dermatomyositis/. Accessed: 10 May 2021.
2.
Myositis Support and Understanding Association Inc. Available from: 
https://understandingmyositis.org/types-of-myositis/dermatomyositis/?gclid=CIXP-
fLSns8CFYM9gQodSZIDlA. Accessed: 10 May 2021.
3.
Fasano S, Alves SC, Isenberg DA. Current pharmacological treatment of idiopathic 
inflammatory myopathies. Expert Rev Clin Pharmacol 2015.
4.
Takayanagi H, Kim S, Matsuo K, et al. “RANKL maintains bone homeostasis through 
c-FOS-dependent induction of interferon-b”. Nature. 2002;416(6882):744-9.
5.
Chiba K, Yoshitsugu H, Kyosaka Y, et al.  A comprehensive review of the 
pharmacokinetics of approved therapeutic monoclonal antibodies in Japan: Are 
Japanese phase I studies still needed?  J Clin Pharmacol. 2014;54(5):483-94.
6.
The Japan Society of Hepatology. Available from: https://www.jsh.or.jp/English/.
Accessed: 10 May 2021.

SAP_001.pdf: 
        Protocol C0251005 (PF-06823859) Statistical Analysis Plan
PFIZER GENERAL BUSINESS 
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Protocol C0251005
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, IMMUNOGENICITY AND PHARMACOKINETICS 
FOLLOWING SINGLE INTRAVENOUS DOSE OF PF-06823859
IN JAPANESE HEALTHY PARTICIPANTS
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
14 APR 2022  


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TABLE OF CONTENTS
1. VERSION HISTORY............................................................................................................4
2. INTRODUCTION .................................................................................................................4
2.1. Study Objectives, Endpoints, and Estimands............................................................4
2.2. Study Design .............................................................................................................5
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................6
3.1. Primary Endpoint(s) ..................................................................................................6
3.2. Secondary Endpoint(s) ..............................................................................................6
3.3. Other Endpoint(s)......................................................................................................7
3.4. Baseline Variables.....................................................................................................7
3.5. Safety Endpoints .......................................................................................................7
3.5.1. Adverse Events .............................................................................................7
3.5.2. Laboratory Data............................................................................................7
3.5.3. Vital Signs ....................................................................................................8
3.5.4. Electrocardiograms.......................................................................................8
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS).....................................................9
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................10
5.1. Hypotheses and Decision Rules ..............................................................................10
5.2. General Methods .....................................................................................................10
5.2.1. Analyses for Binary Endpoints...................................................................10
5.2.2. Analyses for Continuous Endpoints ...........................................................10
5.2.3. Analyses for Categorical Endpoints ...........................................................10
5.3. Methods to Manage Missing Data ..........................................................................10
5.3.1. Safety Data..................................................................................................10
5.3.2. Pharmacokinetic Data.................................................................................10
6. ANALYSES AND SUMMARIES ......................................................................................11
6.1. Primary Endpoint(s) ................................................................................................11
6.1.1. Adverse  Events ..........................................................................................11


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6.1.2. Laboratory Data..........................................................................................12
6.1.3. Vital Signs ..................................................................................................12
6.1.4. Electrocardiograms.....................................................................................12
6.2. Secondary Endpoint(s) ............................................................................................13
6.2.1. Pharmacokinetic Analyses..........................................................................13
6.2.2. Immunogenecity Endpoints........................................................................14
6.3. Other Endpoint(s)....................................................................................................15
6.4. Subset Analyses.......................................................................................................15
6.5. Baseline and Other Summaries and Analyses.........................................................15
6.5.1. Baseline Summaries....................................................................................15
6.5.2. Study Conduct and Participant Disposition................................................15
6.5.3. Study Treatment Exposure .........................................................................15
6.5.4. Concomitant Medications and Nondrug Treatments..................................15
6.6. Safety Summaries and Analyses .............................................................................15
7. INTERIM ANALYSES.......................................................................................................16
8. APPENDICES .....................................................................................................................17
LIST OF TABLES.....................................................................................................................3
APPENDICES ...........................................................................................................................3
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................4
Table 2.
Randomization Scheme ..............................................................................5
Table 3.
Serum PF-06823859 PK Parameters ..........................................................6
Table 4.
PK Parameters to be Summarized Descriptively......................................13
APPENDICES
Appendix 1. Categorical Classes for Vital Signs and ECG of Potential Clinical Concern .....17
Appendix 2. List of Abbreviations...........................................................................................18


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1. VERSION HISTORY
Table 1.
Summary of Changes
Version/
Date
Associated Protocol 
Amendment
Rationale
Specific Changes
1
21JUL2021
Original
26MAY2021
Amendment 1 
09JUL2021
N/A
N/A
2
14APR2022
N/A
Some 
clarifications 
were added.
Section 6.1.1: Added clarification on 
the definition of IRR and viral 
infections.
Sections 6.1.3 and 6.1.4: The 
categorical classes for vital signs and 
ECGs were specified in Appendix 1. 
Overall: Minor edits for the description
maintenance.
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C0251005. This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition or its analysis will also be reflected in a protocol amendment.
2.1. Study Objectives, Endpoints, and Estimands
The following are objectives and endpoints in this study.  Estimand framework is not applied 
to this phase 1 study.
Objectives
Endpoints
Primary: 
Primary: 

To evaluate the safety and tolerability of single 
IV dose of 300 and 900 mg PF-06823859 in 
Japanese healthy participants.

Assessments of AEs/SAEs including IRR, 
infusion sites and viral infections, vital signs, 
ECGs and laboratory tests.
Secondary: 
Secondary: 

To evaluate the PK profile of single IV dose of 
300 and 900 mg PF-06823859 in Japanese 
healthy participants.

To evaluate the immunogenicity of 
PF-06823859.

Serum PF-06823859 PK parameters, as 
permitted by data: Cmax, Cmax (dn), Tmax, AUCinf, 
AUCinf (dn), AUClast, AUClast (dn), AUC14day, 
AUC28day, t1/2, CL, Vss and MRT

Incidence of the development of ADA and NAb.


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  (dn: dose normalized)
2.2. Study Design
This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study to
evaluate the safety, tolerability, immunogenicity and PK of PF-06823859 in Japanese healthy 
adult participants.
Approximately 12 participants are planned to be enrolled into the study. The study consists 
of 2 cohorts, and approximately 5 participants will be randomized to PF-06823859 and 
approximately 1 participant will be randomized to placebo in each cohort. Participants who 
discontinue prior to completion of the study for non-safety related reasons may be replaced at 
the discretion of the investigator upon consultation with the sponsor. Each participant will 
receive PF-06823859 or placebo per the scheme summarized in Table 2.
Table 2.
Randomization Scheme
Cohort
Treatment
Number of participants
1
PF-06823859 300 mg
5
Placebo
1
2
PF-06823859 900 mg
5
Placebo
1
Within 28 days of successful completion of the screening process, eligible participants will 
be enrolled and randomized to receive a single IV infusion of PF-06823859 or placebo. The 
participants in Cohort 2 should be dosed following at least 96 hours safety pause after the 
participants in Cohort 1 have been dosed. Participants will be admitted into the clinical 
research unit (CRU) approximately 1 day prior to dosing and are required to stay overnight in 
the CRU through completion of Day 5 evaluations. Participants will return to the CRU for 
outpatient follow up visits per Schedule of Activities given in the protocol through Day 157. 
Participants may be asked to return for additional follow up visits beyond the anticipated end 
of study visit for safety reasons and/or at the discretion of the investigator.


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3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
Primary endpoints are assessments of AEs/SAEs including IRR, infusion sites and viral 
infections, vital signs, ECGs and laboratory tests.
3.2. Secondary Endpoint(s)
Secondary endpoints are:

Serum PF-06823859 PK parameters, as permitted by data: Cmax, Cmax (dn), Tmax, 
AUCinf, AUCinf (dn), AUClast, AUClast (dn), AUC14day, AUC28day, t1/2, CL, Vss and 
MRT. Definition and method of determination of PK parameters are shown in 
Table 3. PK parameters which will be calculated as permitted by data are also 
specified in Table 3.

Incidence of the development of ADA and NAb.
Table 3.
Serum PF-06823859 PK Parameters
Parameter
Definition
Method of Determination
AUC14day
Area under the serum 
concentration-time profile from 
time 0 to 14 days post-dose (336 
hours)
Linear/Log trapezoidal method
AUC28day
Area under the serum 
concentration-time profile from 
time 0 to 28 days post-dose (672 
hours)
Linear/Log trapezoidal method
AUClast
Area under the serum 
concentration-time profile from 
time 0 to the time of the last 
quantifiable concentration (Clast)
Linear/Log trapezoidal method
AUClast (dn)
Dose normalized AUClast
AUClast/Dose
AUCinf a
Area under the serum 
concentration-time profile from 
time 0 extrapolated to infinite 
time
AUClast + (Clast*/kel),
where Clast* is the predicted 
serum concentration at the last 
quantifiable time point estimated 
from the log-linear regression 
analysis
AUCinf (dn)
Dose normalized AUCinf
AUCinf/Dose
Cmax
Maximum serum concentration
Observed directly from data
Cmax (dn)
Dose normalized Cmax
Cmax/Dose


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Table 3.
Serum PF-06823859 PK Parameters
Parameter
Definition
Method of Determination
Tmax
Time at which Cmax occurs
Observed directly from data as 
time of first occurrence
t1/2 a
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  
CL a
Clearance 
Dose/AUCinf
Vss a
Volume of distribution at steady 
state
CL*MRT
MRT
Mean residence time 
AUMCinf/AUCinf – DOF/2, where 
AUMCinf is the area under the 
moment curve from time 0 
extrapolated to infinity and DOF 
is the duration of the IV infusion.
a. If data permitted. 
3.3. Other Endpoint(s)
N/A
3.4. Baseline Variables
There are no baseline variables used as covariates or stratification factors in this study.
The demographic data will include age, sex, ethnicity, race, weight, body mass index and 
height. If not specified, baseline variables are those collected on Day 1 prior to dosing or last 
measurement during screening visits and Day -1.
3.5. Safety Endpoints
3.5.1. Adverse Events
An adverse event is considered a treatment-emergent adverse event (TEAE) to a given 
treatment if the event starts on or after the first dosing day and time/start time, if collected, 
but before the last dose plus the lag time. The algorithm will not consider any events that 
started prior to the first dose date. If an AE starts on the same day as the first dose date, it 
will be considered treatment emergent unless the CRF data indicates otherwise via explicitly 
recording time for AE onset and treatment dosing. The default lag time of CDISC and Pfizer
Standards (CaPS) will be used for this study.
3.5.2. Laboratory Data
Safety laboratory tests will be performed as described in the protocol.


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To determine if there are any abnormalities of potential clinical concern, the hematology,
chemistry and urinalysis safety tests will be assessed against the criteria specified in the
CaPS. The assessment will take into account whether each participant’s baseline test result is 
within or outside the laboratory reference range for the particular laboratory parameter.
Baseline will be the last pre-dose measurement collected on Day -1.
3.5.3. Vital Signs
Supine systolic and diastolic blood pressure and pulse rate (PR) will be taken at all time 
points listed in the Schedule of Activities given in the protocol. The last pre-dose 
measurement at Day 1 will be used as the baseline.
The maximum decrease and increase from baseline over all measurements taken postdose for
supine systolic and diastolic blood pressures will be determined. The maximum increasefrom 
baseline will be calculated by first subtracting the baseline value from each postdose
measurement to give the change from baseline. The maximum of these values over the entire
study will then be selected, except in the case where a participant 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 change 
from baseline. In cases where a subject does not show a decrease, the minimum increase 
should be taken.
3.5.4. Electrocardiograms
Standard 12-lead ECGs will be taken at all time points listed in the Schedule of Activities
given in the protocol. The last pre-dose measurement at Day 1 will be used as the baseline.
The QT, QTc, PR, QRS and heart rate 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 maximum absolute value (postdose) and the maximum increase from baseline will be 
determined over all measurements taken postdose for QTcF, PR and QRS.
The maximum increase from baseline will be calculated by first subtracting the baseline
value from each postdose measurement to give the change from baseline. The maximum of
these values over the respective period will then be selected, except in the case where a
participant does not show an increase. In such an instance, the minimum decrease should be
taken.


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4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
Participant Analysis 
Set
Description
Enrolled/Randomly 
assigned to study 
intervention 
"Enrolled" means a participant's, or their legally authorized 
representative’s, agreement to participate in a clinical study 
following completion of the informed consent process.  
Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless otherwise 
specified by the protocol. A participant will be considered 
enrolled if the informed consent is not withdrawn prior to 
participating in any study activity after screening.
Safety Analysis Set
All participants randomly assigned to study intervention and 
who take at least 1 dose of study intervention. Participants 
will be analyzed according to the product they actually 
received.
PK concentration
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention and in whom at 
least 1 serum sample concentration value of PF-06823859 is 
reported.
PK parameter
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention and who have at 
least 1 of the PK parameters of PF-06823859 of interest 
calculated.
Immunogenicity
All participants randomly assigned to study intervention who 
received at least 1 dose of study intervention with at least one 
post-treatment anti-drug (PF-06823859) antibody 
determination.
If a participant receives a treatment that is not consistent with the treatment they are
randomly assigned to, then the participant will be reported under the treatment that the
participant actually received for all PK, immunogenicity and safety analyses, where 
applicable.


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5. GENERAL METHODOLOGY AND CONVENTIONS
This is a double-blind and sponsor-open study. As this is a sponsor-open study, the sponsor 
may conduct unblinded reviews of the data during the course of the study for the purpose of 
safety assessment, facilitating PK/PD modeling, and/or supporting clinical development.  
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.  
Final analysis will follow the official database release.
5.1. Hypotheses and Decision Rules
There are no statistical hypotheses or decision rules.
5.2. General Methods
All data will be descriptively summarized by treatment (PF-06823859 300 mg, PF-06823859
900 mg, and placebo). Data from placebo in Cohort 1 and Cohort 2 will be pooled for all 
analyses.
5.2.1. Analyses for Binary Endpoints
Number and percentage of participants in each category will be used to summarize the binary 
endpoints, if not otherwise specified.
5.2.2. Analyses for Continuous Endpoints
The summary statistics n, arithmetic mean, median, standard deviation (SD), minimum and
maximum will be used to summarize the continuous endpoints, if not otherwise speficied.
5.2.3. Analyses for Categorical Endpoints
Number and percentage of participants in each category will be used to summarize the
categorical endpoints, if not otherwise specified.
5.3. Methods to Manage Missing Data
5.3.1. Safety Data
Missing values in standard summaries of AEs, laboraty data, vital signs, and ECGs will be
imputed according to CaPS.
5.3.2. Pharmacokinetic Data
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.)


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Deviations, Missing Concentrations and Anomalous Values
In summary tables, plots of mean profiles and plots of median profiles, summary statistics
will be calculated setting concentrations to missing if one of the following cases is true:

A concentration has been collected as ND (i.e., not done) or NS (i.e., 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%
(>50%) of the data are missing.
Pharmacokinetic Parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a participant’s concentration data, the parameter
will be coded as NC (i.e., not calculated). (Note that NC values will not be generated beyond
the day that a participant 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.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to an unexpected event such as known loss of drug during IV administration), this will be 
footnoted in summary tables and will not be included in the calculation of summary statistics.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
The primary endpoints will be listed and summarized by treatment (PF-06823859 300 mg, 
PF-06823859 900 mg, and placebo) in accordance with CaPS, where the resulting data 
presentations will consist of participants from the safety analysis set. Data from placebo in 
Cohort 1 and Cohort 2 will be pooled.   
6.1.1. Adverse  Events
Adverse events will be listed and summarized in accordance with CaPS.
IRR (Infusion Related Reaction) will include adverse events potentially related to infusion 
related reaction and will be determined by blind medical review prior to the database release.
The incidence and severity of IRR will be summarized by treatment group. The incidence 
and severity of IRR will also be summarized by system organ class (SOC) and preferred term 


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(PT) by severity. Separate tables will be prepared by all causalities and treatment-related for 
these summaries.
The incidence and clinical significance of infusion site reaction will be summarized by 
treatment group. The incidence and severity of infusion symptoms will also be listed and 
summarized by treatment group. The detail on infusion site reaction collected in CRF will 
also be listed.
Viral infections will include adverse events which are specified by the latest targeted medical 
events (TMEs) related to infections for C025 project. The incidence and severity of viral 
infections will be summarized by treatment group. The incidence and severity of viral 
infections will also be summarized by SOC and PT by severity.   Separate tables will be 
prepared by all causalities and treatment-related for these summaries.
6.1.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with CaPS.  
Baseline is as defined in Section 3.5.2. 
6.1.3. Vital Signs
Absolute values and changes from baseline in supine systolic and diastolic blood pressure
and pulse rate will be summarized by treatment and visits, according to CaPS. Tables will be 
paged by parameter. Baseline is as defined in Section 3.5.3.
Maximum and minimum absolute values and changes from baseline for vital signs will also 
be summarized by treatment using categories as defined in Appendix 1. Numbers and 
percentages of participants meeting the categorical criteria will be provided. All planned and 
unplanned postdose timepoints will be counted in these categorical summaries. All values 
meeting the criteria of potential clinical concern will be listed.
If necessary, maximum increases or decreases in vital signs may be summarized in addition 
to the above.
6.1.4. Electrocardiograms
Absolute values and changes from baseline for the ECG parameters (QT interval, heart rate, 
QTcF interval, PR interval, and QRS interval) will be summarized by treatment and visits 
following the CaPS. Tables will be paged by parameter. Baseline is as defined in Section 
3.5.4.  
Maximum increase from baseline for QTcF interval, PR and QRS over all measurements will 
be summarized by treatment group, according to CaPS.
ECG endpoints and changes from baseline (QTcF, PR and QRS) will also be summarized by 
cohort and treatment using categories as defined in Appendix 1. The number (%) of 


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participants meeting the categorical criteria will be provided. All planned and unplanned 
postdose timepoints will be counted in these categorical summaries. All values meeting the 
criteria of potential clinical concern will be listed. 
6.2. Secondary Endpoint(s)
6.2.1. Pharmacokinetic Analyses
PK parameters for PF-06823859 following single-dose administration will be derived from 
the serum concentration-time profiles using noncompartmental methods, as data permit.
The PK parameters will be summarized descriptively by treatment group in accordance with 
Pfizer data standards, as data permit. Missing values will be handled as detailed in Section 
5.3. Each PK parameter will be summarized by treatment group and will include the set of 
summary statistics as specified in the table below:
Table 4.
PK Parameters to be Summarized Descriptively
Parameter
Summary Statistics
Cmax, Cmax (dn), AUCinf, AUCinf
(dn), AUClast, AUClast (dn), 
AUC14day, AUC28day, MRT, Vss, CL
N, arithmetic mean, median, standard deviation
(SD), percent coefficient of variation (%CV),
minimum, maximum, geometric mean and
geometric %CV.
Tmax
N, median, minimum, maximum
t1/2
N, arithmetic mean, median, SD, %CV, minimum,
maximum.
dn: dose normalized
There will be summary tables presenting all PK parameters.
To assess the relationship between the PK parameters and dose, dose normalized AUCinf,
AUClast and Cmax will be plotted against dose, and will include individual participant values 
and the geometric means for each dose. Geometric means will have a different symbol than 
the individual values. The values will be dose normalized (to 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 and that data from both cohorts are presented on 
the plot.
Supporting data from the estimation of t1/2 and AUCinf will be listed by analyte where
applicable: terminal phase rate constant (kel); goodness of fit statistic from the log-linear
regression (r2); the percent of AUCinf based on extrapolation (AUCextrap%); and the first, last,
and number of time points used in the estimation of kel. This data may be included in the
clinical study report.


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Presentations for PF-06823859 concentrations will include:

a listing of all concentrations sorted by subject ID, cohort, dose and nominal time
postdose. The concentration listing will also include the actual times. Deviations
from the nominal time will be given in a separate listing.

a summary of concentrations by dose and nominal time postdose, where the
set of statistics will include n, mean, median, SD, %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 postdose by dose (all treatments on the same plot per scale, based on
the summary of concentrations by dose and time postdose).

mean concentrations time plots (on both linear and semi-log scales) against nominal
time postdose by dose (all treatments on the same plot per scale, based on
the summary of concentrations by dose and time postdose).

individual concentration time plots by dose (on both linear and semi-log
scales) against actual time postdose (there will be separate spaghetti plots for each
dose per scale).

individual concentration time plots by participant (on both linear and semi-log scales)
against actual time postdose [there will be separate plots for each participant (containing
all doses) per scale].
The length of time used for the x-axes of these plots will be decided on review of the data,
and will depend on how long PF-06823859 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 participant plots by time, the actual PK sampling time will 
be used.
6.2.2. Immunogenecity Endpoints
The incidence of the development of ADA and NAb will be listed and summarized for
participants in the immunogenicity analysis set. Presentations for immunogenecity will 
include:

Summary of ADA and NAb by sample

Summary of ADA and NAb incidence over time

Summary of incidence of ADA and NAb by dose and time postdose

Summary of cumulative incidence of ADA and NAb by dose and time postdose

Impact of ADA and NAb status on PF-06823859 concentrations


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
Summary of participants with ADA negative and PK > assay tolerance value at last 
sampling point
Immunogenicity assay titers will be used to determine incidence for ADA and NAb. Titer
values will also be listed.
6.3. Other Endpoint(s)
N/A
6.4. Subset Analyses
No subset analysis will be conducted for this study.
6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Demographic and baseline characteristics (age, sex, ethnicity, race, weight, body mass index 
and height) collected prior to the first dose of the study drug will be summarized following 
the CaPS.
6.5.2. Study Conduct and Participant Disposition
The following participant dispositions will be summarized.

A summary of participant discontinuations up to end of study;

Summary of participant dispositions analyzed for PK, immunogenicity, as well as for 
safety;

Summary of numbers of participant treated by treatment group.
Data will be reported following the CaPS.
6.5.3. Study Treatment Exposure
Study treatment exposure will be listed.
6.5.4. Concomitant Medications and Nondrug Treatments
All concomitant medications as well as nondrug treatments will be summarized following the 
CaPS.
6.6. Safety Summaries and Analyses
The details of safety analyses are described in the Section 6.1.


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7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study. As this is a sponsor-open
study, the sponsor may conduct unblinded reviews of the data during the course of the study 
for the purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical 
development.


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8. APPENDICES
Appendix 1. Categorical Classes for Vital Signs and ECG of Potential Clinical Concern
Categories for Vital Signs
Systolic BP (mm Hg)
min. <90
Diastolic BP (mm Hg)
min. <50
Pulse rate (bpm)
min. <40
max. >120
Systolic BP (mm Hg) 
change from baseline
max. increase 30
max. decrease 30
Diastolic BP (mm Hg) 
change from baseline
max. increase 20
max. decrease 20
Categories for PR and QRS
PR (ms)
max. 300
QRS (ms)
max. 140
PR (ms) increase 
from baseline
Baseline >200 and max. 25% increase or 
Baseline 200 and max. 50% increase
QRS (ms) increase 
from baseline
50% increase
Categories for QT
Absolute value
500
Categories for QTcF
Degree of 
Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
450 and <480
480 and <500
500
Increase from 
baseline
30 and <60
60
Measurements that fulfill these criteria are to be listed in report.


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Appendix 2. List of Abbreviations
Abbreviation Term
ADA
antidrug antibodies
AE
adverse event
AUC
area under the curve
AUC14day
AUC from time 0 to 14 days post-dose
AUC28day
AUC from time 0 to 28 days post-dose
AUCextrap%
percent of AUCinf based on extrapolation
AUCinf
AUC from time 0 extrapolated to infinite time
AUClast
AUC from time 0 to the time of the last quantifiable concentration
BLQ
below the limit of quantitation
CaPS
CDISC and Pfizer Standards
CDISC
Clinical Data Interchange Standards Consortium
Cmax
maximum observed concentration
CL
clearance
CRF
case report form
CRU
clinical research unit
dn
dose normalized
ECG
electrocardiogram
HR
heart rate
IRR
infusion related reaction
IV
intravenous(ly)
kel
terminal phase rate constant
LLQ
lower limit of quantitation
MRT
mean residence time
N/A
not applicable
NAb
neutralizing antibodies
NC
not calculated
ND
not done
NS
no sample
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PR
pulse rate
PT
preferred term
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SOC
system organ class


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Abbreviation Term
t1/2
terminal phase half-life
TEAE
treatment-emergent adverse event
TME
targeted medical event
Tmax
time to reach Cmax
Vss
volume at steady state