Clinical trial NCT05257798
Conditions: Healthy
Sponsor: Pfizer
Start date: 2022-02-28; Completion date: 2023-03-21
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this clinical trial is to learn if the study medicine (called PF-06823859) is safe and how it is processed in healthy Chinese participants. This study is seeking participants who:

* Are between 18 to 45 years of age, inclusive, at the time of signing the Informed Consent Document (ICD).
* Are Chinese participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12 lead ECG (electrocardiogram).
* Have a BMI (body mass index) of 19 to 27 kg/m2 (inclusive); and a total body weight \>50 kg (110 lb).

All participants in this study will receive PF-06823859 or a placebo. A placebo does not have any medicine in it but looks just like the medicine being studied. PF-06823859 will be given as an infusion directly into a vein. We will compare the experiences of people receiving PF-06823859 to those of people who do not. This will help us determine if PF-06823859 is safe and how it behaves inside the human body.

Participants will take part in this study for up to 157 days. During this time, they will receive PF-06823859 or placebo and be observed for any effects.

Detailed description:
This is a Phase 1, randomized, double blind, sponsor open, placebo controlled study to evaluate the PK, safety, and tolerability following a single dose of PF 06823859 (900 mg) in healthy Chinese participants.

Arms: arm 1: Participants will receive 900 mg of PF-06823859 via intravaneous (IV). arm 2: Participants will receive placebo via IV.
Interventions: intervention 1: IFN-β inhibitor treatment intervention 2: Placebo
Intervention descriptions: intervention 1: PF-06823859 (IFN-β inhibitor) 100 mg/mL solution for injection intervention 2: Placebo for PF-06823859, 0 mg/mL solution for injection

Protocol documents:
Prot_000.pdf: 
PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified. 
 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, 
PLACEBO-CONTROLLED, STUDY TO EVALUATE THE PHARMACOKINETICS, 
SAFETY, AND TOLERABILITY FOLLOWING A SINGLE DOSE OF PF-06823859 
IN HEALTHY CHINESE PARTICIPANTS 
 
 
 
Study Intervention Number: 
Study Intervention Name: 
US IND Number: 
PF-06823859 
N/A 
N/A 
EudraCT Number: 
N/A 
ClinicalTrials.gov ID: 
N/A 
Protocol Number: 
C0251007 
Phase: 
1 
Brief Title: A Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability 
Following a Single Dose of PF-06823859 in Healthy Chinese Participants 
 
 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 2 
 
 
Document History 
 
Document 
Version Date 
Amendment 1 
10 May 2022 
Original protocol 
25 Jun 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 (10 May 2022) 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Section 1.1. 
Synopsis, 
Subsection 
“Number of 
Participants”; 
Section 4.1. 
Overall 
Design, 
Subsection 
“Number of 
Participants”; 
Section 4.2. 
Scientific 
Rationale for 
Study Design 
The following statement 
was updated: 
Original statement: 
If more than 
2 participants discontinue 
or withdraw before 
completing at least the 
follow-up visit at 
Day 100, participants 
may be replaced at the 
discretion of the 
investigator upon 
alignment with the 
sponsor. 
Updated statement: 
If more than 
2 participants discontinue 
or withdraw before 
completing at least the 
follow-up visit at 
Day 100, or if there are 
participants whose PK 
samples are considered to 
be non-evaluable with 
respect to the primary PK 
objective, additional 
To allow additional 
participants to enroll in 
the study in the event of 
participants whose PK 
samples are considered 
to be non-evaluable 
with respect to the 
primary PK objective or 
if more than 
2 participants 
discountinue or 
withdraw before 
completing at least the 
follow-up visit at 
Day 100, to ensure 
approximate 
10 participants could 
provide evaluable PK 
samples for no less than 
Day 100 follow-up 
visit. 
Substantial 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 3 
 
 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
participants may be 
enrolled upon alignment 
between the sponsor and 
the investigator such that 
approximate 
10 participants could 
provide evaluable PK 
samples for no less than 
Day 100 follow-up visit. 
For participants whose 
PK samples are 
considered to be non- 
evaluable with respect to 
the primary PK 
objective, their PK 
sample collection will 
stop for ethic 
consideration. 
Section 9.5. 
Sample Size 
Determination 
The following statement 
was added: 
If more than 
2 participants discontinue 
or withdraw before 
completing at least the 
follow-up visit at 
Day 100, or if there are 
participants whose PK 
samples are considered to 
be non-evaluable with 
respect to the primary PK 
objective, additional 
participants may be 
enrolled upon alignment 
between the sponsor and 
the investigator such that 
approximate 
10 participants could 
provide evaluable PK 
samples for no less than 
Day 100 follow-up visit. 
To allow additional 
participants to enroll in 
the study in the event of 
participants whose PK 
samples are considered 
to be non-evaluable 
with respect to the 
primary PK objective or 
if more than 
2 participants 
discountinue or 
withdraw before 
completing at least the 
follow-up visit at 
Day 100, to ensure 
approximate 
10 participants could 
provide evaluable PK 
samples for no less than 
Day 100 follow-up 
visit. 
Substantial 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 4 
 
 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Section 1.3. 
Schedule of 
Activities 
ECG was updated to be 
measured on Day -1 
instead of Day 1. 
To keep consistent with 
Exclusion Criteria #18 
evaluation 
(Day -1/baseline) and to 
align with site practice. 
Nonsubstantial 
Section 1.3. 
Schedule of 
Activities 
In the footnote “h”, the 
statement of “at least 
48 hours before and” was 
removed for COVID-19 
questionnaire. 
To align with site 
practice. 
Nonsubstantial 
Section 5.2. 
Exclusion 
Criteria #2 
The word “syphilis” was 
added to statement, the 
updated statement being: 
History of HIV infection, 
hepatitis B, or hepatitis 
C; positive testing for 
HIV, syphilis, HBsAg, 
or HCVAb. 
To keep consistent with 
assessment requirement 
listed in Section 1.3 
Schedule of Activities. 
Nonsubstantial 
Section 5.2. 
Exclusion 
Criteria #17 
Update “≤50 bpm” to 
“<50 bpm”. 
To correct a typo. 
Nonsubstantial 
Section 8.2.4. 
Electrocardio- 
gram 
The original statement of 
“Appendix 7” was 
updated to “Appendix 6”: 
ECG values of potential 
clinical concern are listed 
in Appendix 6. 
To correct a typo. 
Nonsubstantial 
Section 8.2.5. 
Clincial Safety 
Laboratory 
Assessments 
The original statement of 
“Appendix 6” was 
updated to “Appendix 5”: 
See Appendix 5 for 
suggested actions and 
follow-up assessments in 
the event of potential 
drug-induced liver injury. 
To correct a typo. 
Nonsubstantial 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 5 
 
 
 
Section # and 
Name 
Description of Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Section 9.4. 
Interim 
Analyses 
In the second sentence of 
the paragraph, the word 
“However” was deleted 
and “agency 
communication” was 
added, the updated 
sentence being: 
As this is an 
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, agency 
communication, and/or 
supporting clinical 
development. 
The word “However” 
was deleted to align 
with mandatory 
template text. 
The wording “agency 
communication” was 
added to reflect updated 
purpose of potential 
unblinded data review. 
Nonsubstantial 
Section 10.2. 
Appendix 2: 
Clinical 
Laboratory 
Tests 
Syphilis test was added 
to “Other” safety 
laboratory assessment. 
To keep consistent with 
assessment requirement 
listed in Section 1.3 
Schedule of Activities. 
Nonsubstantial 
Section 10.4.4. 
Contraception 
Methods 
The word “Injectable” 
was removed from 
“6. Combined [estrogen- 
and progestogen- 
containing] hormonal 
contraception associated 
with inhibition of 
ovulation”. 
To align with protocol 
template updates. 
Nonsubstantial 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 6 
 
 
CCI 
CCI 
CCI 
TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 10 
1. PROTOCOL SUMMARY ................................................................................................... 11 
1.1. Synopsis ................................................................................................................... 11 
1.2. Schema..................................................................................................................... 12 
1.3. Schedule of Activities .............................................................................................. 13 
2. INTRODUCTION ................................................................................................................ 16 
2.1. Study Rationale ........................................................................................................ 16 
2.2. Background .............................................................................................................. 16 
2.2.1. Nonclinical Overview ................................................................................. 16 
2.2.2. Clinical Overview ....................................................................................... 17 
 
 
 
2.3. Benefit/Risk Assessment ........................................................................................ 18 
3. OBJECTIVES AND ENDPOINTS ..................................................................................... 20 
4. STUDY DESIGN ................................................................................................................. 20 
4.1. Overall Design ......................................................................................................... 20 
4.2. Scientific Rationale for Study Design ..................................................................... 21 
4.2.1. Choice of Contraception/Barrier Requirements .......................................... 22 
4.3. Justification for Dose ............................................................................................... 22 
4.4. End of Study Definition ........................................................................................... 22 
5. STUDY POPULATION ...................................................................................................... 23 
5.1. Inclusion Criteria ..................................................................................................... 23 
5.2. Exclusion Criteria .................................................................................................... 24 
5.3. Lifestyle Considerations .......................................................................................... 28 
5.3.1. Meals and Dietary Restrictions ................................................................... 28 
5.3.2. Caffeine, Alcohol, and Tobacco .................................................................. 28 
5.3.3. Activity ....................................................................................................... 28 
5.3.4. Contraception .............................................................................................. 28 
5.4. Screen Failures ......................................................................................................... 29 


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Protocol C0251007 
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6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................. 29 
6.1. Study Intervention(s) Administered ........................................................................ 29 
6.1.1. Administration ............................................................................................ 29 
6.1.1.1. Intravenous Infusion Discontinuation ....................................... 30 
6.2. Preparation, Handling, Storage, and Accountability .............................................. 30 
6.2.1. Preparation and Dispensing ........................................................................ 31 
6.3. Measures to Minimize Bias: Randomization and Blinding .................................... 32 
6.3.1. Allocation to Study Intervention ................................................................ 32 
6.3.2. Breaking the Blind ..................................................................................... 32 
6.4. Study Intervention Compliance .............................................................................. 32 
6.5. Dose Modification .................................................................................................. 33 
6.6. Continued Access to Study Intervention After the End of the Study ..................... 33 
6.7. Treatment of Overdose ........................................................................................... 33 
6.8. Concomitant Therapy ............................................................................................. 33 
6.8.1. Rescue Medicine ........................................................................................ 34 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................... 34 
7.1. Discontinuation of Study Intervention .................................................................... 34 
7.2. Participant Discontinuation/Withdrawal From the Study ...................................... 34 
7.2.1. Withdrawal of Consent .............................................................................. 35 
7.3. Lost to Follow-up ................................................................................................... 35 
8. STUDY ASSESSMENTS AND PROCEDURES .............................................................. 36 
8.1. Efficacy Assessments ............................................................................................. 37 
8.2. Safety Assessments ................................................................................................. 37 
8.2.1. Physical Examinations ............................................................................... 37 
8.2.2. Chest X-ray ................................................................................................ 38 
8.2.3. Vital Signs .................................................................................................. 38 
8.2.3.1. Temperature .............................................................................. 38 
8.2.4. Electrocardiograms ..................................................................................... 38 
8.2.5. Clinical Safety Laboratory Assessments .................................................... 39 
8.2.5.1. HBV Testing ............................................................................. 41 
8.2.6. Tuberculosis Test ....................................................................................... 41 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 8 
 
 
8.2.7. Viral Surveillance ........................................................................................ 42 
8.2.8. COVID-19 Specific Assessments ............................................................... 42 
8.2.9. Pregnancy Testing ....................................................................................... 42 
8.2.10. Infusion Site Assessment .......................................................................... 43 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................. 43 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ....... 43 
8.3.1.1. Reporting SAEs to Pfizer Safety ............................................... 44 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF ................... 44 
8.3.2. Method of Detecting AEs and SAEs ........................................................... 44 
8.3.3. Follow-Up of AEs and SAEs ...................................................................... 44 
8.3.4. Regulatory Reporting Requirements for SAEs ........................................... 45 
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure ..................................................... 45 
8.3.5.1. Exposure During Pregnancy ...................................................... 45 
8.3.5.2. Exposure During Breastfeeding ................................................. 47 
8.3.5.3. Occupational Exposure .............................................................. 48 
8.3.6. Cardiovascular and Death Events ................................................................ 48 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................. 48 
8.3.8. Adverse Events of Special Interest .............................................................. 48 
8.3.8.1. Lack of Efficacy ........................................................................ 48 
8.3.9. Medical Device Deficiencies ...................................................................... 48 
8.3.10. Medication Errors ...................................................................................... 48 
8.4. Pharmacokinetics ..................................................................................................... 49 
8.5. Genetics ................................................................................................................... 50 
8.6. Biomarkers ............................................................................................................... 50 
8.7. Immunogenicity Assessments ................................................................................. 50 
8.8. Health Economics .................................................................................................... 51 
9. STATISTICAL CONSIDERATIONS ................................................................................. 51 
9.1. Statistical Hypotheses .............................................................................................. 51 
9.2. Analysis Sets ............................................................................................................ 51 
9.3. Statistical Analyses .................................................................................................. 52 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 9 
 
 
9.3.1. General Considerations .............................................................................. 52 
9.3.2. Pharmacokinetic Analyses of PF-06823859 .............................................. 52 
9.3.3. Immunogenicity Analyses.......................................................................... 53 
9.3.4. Other Safety Analyses ................................................................................ 53 
9.3.4.1. Electrocardiogram Analyses ..................................................... 53 
9.4. Interim Analyses ..................................................................................................... 54 
9.5. Sample Size Determination .................................................................................... 54 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.......................................................................................................... 55 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............... 55 
10.1.1. Regulatory and Ethical Considerations .................................................... 55 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................ 55 
10.1.2. Financial Disclosure ................................................................................. 56 
10.1.3. Informed Consent Process ....................................................................... 56 
10.1.4. Data Protection ......................................................................................... 57 
10.1.5. Committees Structure ............................................................................... 57 
10.1.5.1. Data Monitoring Committee ................................................... 57 
10.1.6. Dissemination of Clinical Study Data ...................................................... 57 
10.1.7. Data Quality Assurance ............................................................................ 59 
10.1.8. Source Documents ................................................................................... 60 
10.1.9. Study and Site Start and Closure .............................................................. 60 
10.1.10. Publication Policy .................................................................................. 61 
10.1.11. Sponsor’s Qualified Medical Personnel ................................................. 62 
10.2. Appendix 2: Clinical Laboratory Tests ................................................................ 63 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ..................................................................... 64 
10.3.1. Definition of AE ...................................................................................... 64 
10.3.2. Definition of an SAE ................................................................................ 65 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ........................................................................... 66 
10.3.4. Reporting of SAEs ................................................................................... 70 
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................ 71 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
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10.4.1. Male Participant Reproductive Inclusion Criteria .................................... 71 
10.4.2. Female Participant Reproductive Inclusion Criteria ................................. 71 
10.4.3. Woman of Childbearing Potential ............................................................. 72 
10.4.4. Contraception Methods ............................................................................. 73 
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments ........ 75 
10.6. Appendix 6: ECG Findings of Potential Clinical Concern .................................... 77 
10.7. Appendix 7: Abbreviations .................................................................................... 79 
11. REFERENCES ................................................................................................................... 83 
LIST OF TABLES 
Table 1. 
Definition of Serum PK Parameters for PF-06823859 .............................. 52 
Table 2. 
Protocol-Required Safety Laboratory Assessments .................................. 63 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 11 
 
 
1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: A Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability 
Following a Single Dose of PF-06823859 in Healthy Chinese Participants 
Rationale 
The purpose of this study is to evaluate the single-dose PK, safety, and tolerability of 
PF-06823859 after single IV administration to healthy adult Chinese participants. The 
information of PK, safety, and tolerability in healthy Chinese participants is being collected 
to support future PF-06823859 clinical development as well as drug registration in China. 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To evaluate the PK profile of single IV dose of 
900 mg PF-06823859 in healthy Chinese 
participants. 
• 
To determine the safety and tolerability of 
single IV dose of 900 mg PF-06823859 in 
healthy Chinese participants. 
• 
Serum PF-06823859 primary PK parameters, as 
permitted by data: Cmax, Tmax, AUC14day, 
AUC28day, AUCinf, and t½. 
• 
Assessments of AEs/SAEs including infusion 
site reactions and viral infections, vital signs, 
ECGs and laboratory tests. 
Secondary: 
Secondary: 
• 
To further evaluate the PK of PF-06823859 
• 
To evaluate the immunogenicity of 
PF-06823859. 
• 
Serum PF-06823859 PK parameters, as 
permitted by data: Cmax (dn), AUClast, 
AUClast (dn), AUCinf (dn), CL, Vz, and MRT. 
• 
Incidence of the development of ADA and Nab. 
 
Overall Design 
This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study to 
evaluate the PK, safety, and tolerability following a single dose of PF-06823859 (900 mg) in 
healthy Chinese participants. 
Number of Participants 
Approximately 12 participants will be enrolled into the study. Approximately 10 participants 
will be randomized to PF-06823859 and approximately 2 participants will be randomized to 
placebo. 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 12 
 
 
If more than 2 participants discontinue or withdraw before completing at least the follow-up 
visit at Day 100, or if there are participants whose PK samples are considered to be non- 
evaluable with respect to the primary PK objective, additional participants may be enrolled 
upon alignment between the sponsor and the investigator such that approximate 
10 participants could provide evaluable PK samples for no less than Day 100 follow-up visit. 
For participants whose PK samples are considered to be non-evaluable with respect to the 
primary PK objective, their PK sample collection will stop for ethic consideration. 
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. 
Participants will be admitted into the CRU approximately 1 day prior to dosing and are 
required to remain 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 
Statistical objective is exploratory. Only descriptive analyses will be performed. 
1.2. Schema 
Not applicable. 


PF-06823859 
Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 13 
 
 
 
1.3. Schedule of Activities 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
 
Visit Identifiera 
Abbreviations used in this table may be 
found in Appendix 7. 
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 
100 127 157 
- 
Visit Window (days) 
- 
- 
- 
- 
- 
- 
- 
1 
±1 
±1 
±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 illicit 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 and 
weight at screening, only)c 
X 
X 
X 
Single 12-Lead ECG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Supine blood pressure, pulse rate and 
temperature 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest radiographd 
X 
X 
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 fast) 
including PT, INR, aPTT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Viral surveillance (CMV, VZV, EBV, 
HHV6, HSV-1, HSV-2) 
X 
X 
X 
X 
X 
X 


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Protocol C0251007 
Final Protocol Amendment 1, 10 May 2022 
PFIZER CONFIDENTIAL 
Page 14 
 
 
 
Visit Identifiera 
Abbreviations used in this table may be 
found in Appendix 7. 
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 
100 127 157 
- 
Visit Window (days) 
- 
- 
- 
- 
- 
- 
- 
1 
±1 
±1 
±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 
Pharmacokinetic 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 fast) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a. 
Day relative to start of study intervention (Day 1). 
b. 
Pre-dose (except for study intervention administration). 
c. 
A full physical examination may be done at screening or Day -1. Brief physical examination to follow-up open AEs after Day -1 may be done. 
d. 
Chest X-ray or other appropriate diagnostic image (ie, CT or MRI) results within 12 weeks 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 continuously monitored for infusion related reactions from start of study intervention administration until the end of infusion. 
f. 
Participants who are HBsAg negative but HBcAb negative and HBsAb positive without unequivocal documentation of prior HBV vaccination or who are HBsAg 
negative but 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 in screening and the participant is enrolled the study, HBV DNA testing must be performed on. If HBV DNA is undetectable in the HBV DNA reflex testing in 
screening and the participant is enrolled the study, HBV DNA testing must be performed on Day 71, 157 and ET. See Section 8.2.5.1. 
g. 
Acceptable IGRA assays are QuantiFERON®-TB Gold In-Tube (QFT-GIT) test and T-SPOT®TB test. A documented TB test performed within 12 weeks prior to Day 1 
is acceptable. Participants with a history of tuberculosis may not require TB testing as per the protocol exclusion criteria in Section 5.2. 
h. 
Check exposure to positive participant, residence or travel in area of high incidence and COVID-19 related signs and symptoms. To be done at each visit. 
i. 
The testing for COVID-19 pathogen by PCR will be performed within 72 hours prior to admission on Day -1. In addition, a subsequent COVID-19 test will be performed 
after 4 days (ie, upon completion of 4 × 24 hours in house), or 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). 


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Visit Identifiera 
Abbreviations used in this table may be 
found in Appendix 7. 
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 
100 127 157 
- 
Visit Window (days) 
- 
- 
- 
- 
- 
- 
- 
1 
±1 
±1 
±3 
±3 
±3 
±3 
±3 
±3 
- 
Hours After Dose 
0b 
1 
2 
6 
12 
24 
48 
72 
96 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
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 DM with added potential for therapeutic 
benefit in SLE. 
2.1. Study Rationale 
The purpose of this study is to evaluate the single-dose PK, safety, and tolerability of 
PF-06823859 after single IV administration to healthy adult Chinese participants. The 
information of PK, safety, and tolerability in healthy Chinese participants is being collected 
to support future PF-06823859 clinical development as well as registration in China. 
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 
In vitro 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. 
In addition, the nonclinical PK profiles of PF-06823859 in the cynomolgus monkey were 
typical for a human IgG mAb in monkeys. Furthermore, the nonclinical safety profile of 
PF-06823859 has been adequately characterized in vitro and in vivo in cynomolgus monkey 
to support progression into clinical trials up to 3 months in duration. 


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CCI 
CCI 
Detailed information concerning the nonclinical studies conducted with PF-06823859 can be 
found in the IB. 
2.2.2. Clinical Overview 
As of the protocol date, the Phase 1, randomized, double-blind, third-party open, 
placebo-controlled, dose escalating study to evaluate the safety, tolerability, 
pharmacokinetics and pharmacodynamics of single and multiple intravenous and 
subcutaneous doses of PF-06823859 in healthy participants (C0251001) has been completed. 
In addition, the 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 IB. 
 
 
 
 
 
 
 
 


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CCI 
 
 
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, and PK data for 
further clinical development. 
Nonclinical data to date (Section 2.2) 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 (WOCPB 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 IFN-β.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 
CCI 


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biomarkers. However, the potential for bone effects in developing/growing bones has not 
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 planned 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 IFN-β blockade as 
with any antagonist of Type 1 interferon signaling (eg, anti-IFNAR1, anti-IFN-α, 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. 
The clinical impact of these potential risks will be minimized through the proposed standard, 
intensive, inpatient monitoring of the participants following administration of single, IV dose 
of the study intervention. 
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. 


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3. OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary: 
Primary: 
• 
To evaluate the PK profile of single IV dose of 
900 mg PF-06823859 in healthy Chinese 
participants. 
• 
To determine the safety and tolerability of 
single IV dose of 900 mg PF-06823859 in 
healthy Chinese participants. 
• 
Serum PF-06823859 primary PK parameters, as 
permitted by data: Cmax, Tmax, AUC14day, 
AUC28day, AUCinf, and t½, 
• 
Assessments of AEs/SAEs including infusion 
site reactions and viral infections, vital signs, 
ECGs and laboratory tests. 
Secondary: 
Secondary: 
• 
To further evaluate the PK of PF-06823859 
• 
To evaluate the immunogenicity of 
PF-06823859. 
• 
Serum PF-06823859 PK parameters, as 
permitted by data: Cmax (dn), AUClast, 
AUClast (dn), AUCinf (dn), CL, Vz, 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, single arm 
study to evaluate the PK, safety, and tolerability following a single dose of PF-06823859 
(900 mg) in healthy Chinese participants. 
Number of Participants 
Approximately 12 participants will be enrolled into the study. Approximately 10 participants 
will be randomized to PF-06823859 and approximately 2 participants will be randomized to 
placebo. 
If more than 2 participants discontinue or withdraw before completing at least the follow-up 
visit at Day 100, or if there are participants whose PK samples are considered to be non- 
evaluable with respect to the primary PK objective, additional participants may be enrolled 
upon alignment between the sponsor and the investigator such that approximate 
10 participants could provide evaluable PK samples for no less than Day 100 follow-up visit. 
For participants whose PK samples are considered to be non-evaluable with respect to the 
primary PK objective, their PK sample collection will stop for ethic consideration. 
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. 
Participants will be admitted into the CRU approximately 1 day prior to dosing and are 
required to remain in the CRU through completion of Day 5 evaluations. Participants will 
return to the CRU for outpatient follow-up visits through Day 157. 


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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. 
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor will conduct unblinded reviews of the safety, PK, and immunogenicity data 
through Day 28 after treatment administration to preliminarily assess any ethnic differences 
between Chinese and non-Chinese to support China joining future global PF-06823859 
clinical development. 
4.2. Scientific Rationale for Study Design 
This study is designed to characterize the PK, safety, and tolerability of PF-06823859 after 
single IV dose administration in healthy Chinese participants. 
To date, no PK or safety data of PF-06823859 in Chinese are available. Although there is no 
expected relevant PK difference between Chinese and non-Chinese because monoclonal 
antibodies are generally known for the absence of ethnic differences in their distribution and 
elimination, similar to that of endogenous IgG,5 it is still important to characterize PK and 
establish safety in Chinese participants to support future PF-06823859 clinical development 
as well as drug registration in China. Information collected from this study allows 
comparison of PK and safety profiles of PF-06823859 in Chinese and non-Chinese 
participants. 
Single-dose rather than repeated dosing is planned in the study due to the long PF-06823859 
terminal half-life as well as the steady-state PK can be well predicted from single dose data 
based on information of Study C0251001. The study duration and frequency of each 
assessment were decided based on information of Study C0251001. 
In order to sufficiently evaluate PK, safety, and tolerability of PF-06823859 in Chinese 
participants while at the same time considering the clinical practice and minimal necessity 
for PK evaluation, if more than 2 participants discontinue or withdraw before completing at 
least the follow-up visit at Day 100, or if there are participants whose PK samples are 
considered to be non-evaluable with respect to the primary PK objective, additional 
participants may be enrolled upon alignment between the sponsor and the investigator such 
that approximate 10 participants could provide evaluable PK samples for no less than 
Day 100 follow-up visit. For participants whose PK samples are considered to be non- 
evaluable with respect to the primary PK objective, their PK sample collection will stop for 
ethic consideration. 
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 IFN- blockade as with any antagonist of Type 1 interferon signaling (eg, 


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CCI 
anti-IFNAR1, anti-IFN-, 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). 
4.3. Justification for Dose 
The proposed single IV dose level is 900 mg. The dose is selected based on the safety and 
tolerability in Study C0251001 and the doses of the Phase 2 study (Study C0251002) that is 
ongoing in patients with DM, to compare safety and PK among Chinese and non-Chinese. 
PF-06823859 dose of 900 mg has been selected to evaluate the PK, safety, and tolerability of 
PF-06823859 in healthy Chinese 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. In the ongoing Phase 2 study (C0251002), PF-06823859 doses of CCI 
 Q4W and 
CCI 
 Q4W are being evaluated with the primary objective being to characterize the effect 
of PF-06823859 in DM patients. 
 
 
Based on the above data, 900 mg is selected to evaluate PK, safety, and tolerability of 
PF-06823859 in healthy Chinese participants. 
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. 


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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 18 to 45 years of age, inclusive, at the time of 
signing the ICD. 
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants. 
Type of Participant and Disease Characteristics: 
2. Male and female Chinese participants who are overtly healthy as determined by 
medical evaluation including medical history, physical examination, laboratory tests, 
and 12-lead ECG. 
3. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures. 
Weight: 
4. BMI of 19 to 27 kg/m2 (inclusive); and a total body weight >50 kg (110 lb). 
Informed Consent: 
5. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol. 


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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 B, or hepatitis C; positive testing for HIV, 
syphilis, HBsAg, or HCVAb. Hepatitis B vaccination is allowed. 
For hepatitis B, all participants must undergo testing for HBsAg, HBcAb, and 
HBsAb. 
• 
Participants who are HBsAg positive will be excluded. 
• 
Participants who are negative for all 3 serology tests may be eligible. 
• 
HBsAg negative, HBcAb positive, and HBsAb negative participants are to be 
excluded from the study. 
• 
Participants who are HBsAg negative, HBcAb negative and HBsAb positive and 
provide documentation of prior HBV vaccination, may be eligible for the study 
and will not require HBV DNA monitoring during the study. 
• 
Participants who are HBsAg negative, HBcAb negative and HBsAb positive 
without documentation of prior HBV vaccination AND participants who are 
HBsAg negative, HBcAb positive, and HBsAb positive, will have HBV DNA 
assessed at screening. 
• If HBV DNA is detectable, participants will be excluded. 
• If HBV DNA is not detectable, participants may be eligible. If the participant 
is included in the study, for subsequent visits HBV DNA testing must be 
performed according to the SoA. 
3. History of autoimmune disorders. 
4. History of allergic or anaphylactic reaction to a therapeutic drug. 
5. History of recent active infections within 28 days prior to the screening visit. 
6. Participants with a fever within 7 days prior to dosing. 


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7. Infected with Mycobacterium TB as defined by any of the following: 
• A positive IGRA test performed at or within the 12 weeks prior to Day 1 is 
exclusionary; a negative test is required for eligibility. The following are 
acceptable IGRA assays: T-SPOT TB test, QuantiFERON-TB Gold 
In-Tube test (QFT-GIT), QuantiFERON-TB Gold test (QFT-G) or 
QuantiFERON-TB Gold Plus test (QFT-G Plus). In participants with a 
history of BCG vaccination, the IGRA test is strongly recommended since the 
Mantoux test (tuberculin, PPD skin test) may be positive due to vaccination. 
• If the results of the IGRA are indeterminate, the test may be repeated 1 time, 
and if a negative result is obtained, enrollment may proceed. A positive test on 
repeat is exclusionary. 
• A chest radiograph should be obtained if not done within the 3 months prior to 
screening. To be considered eligible for the study, the chest radiograph must 
be negative for active TB infection 
• History of either untreated or inadequately treated latent or active TB 
infection. 
• A participant who is currently being treated for active TB infection must be 
excluded from the study. 
• A participant who is being treated for latent TB infection can only be enrolled 
with exclusion of close contacts of multi-drug resistant TB, documentation of 
an adequate treatment regimen, and prior approval of the sponsor. 
8. Contact with positive case of COVID-19 or travel to an area defined as high risk by 
relevant authority in the past 14 days. 
9. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study. 
Prior/Concomitant Therapy: 
10. 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). 
11. Current use of any prohibited concomitant medication(s) or those unwilling/unable to 
use a permitted concomitant medication(s). Refer to Section 6.8 for additional details. 


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12. Recent exposure to any live or attenuated live virus vaccines within 6 weeks of 
Day 1. 
• 
The use of COVID-19 vaccines are allowed. Any live or live attenuated 
COVID-19 vaccine will require a 6-week time period before admission to CRU. 
If the participant receives a COVID-19 vaccine during the study period, this 
should be recorded as a concomitant medication, and standard AE collection and 
reporting processes should be followed in the event of any AEs to the vaccination 
Prior/Concurrent Clinical Study Experience: 
13. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement. 180 days for biologics) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer). 
14. Participants that have received PF-06823859 or any other interferon alpha or 
interferon beta therapy at any time in the past. 
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 or <50 bpm. If the PR is greater than 100 bpm or less than 
50 bpm, the PR should be repeated 2 more times and the average of the three pulse 
rate 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 QTcF 
interval >450 msec, complete LBBB, signs of an acute or indeterminate-age 
myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, 
second or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). 
If the baseline uncorrected QT interval is >450 msec, this interval should be 
rate-corrected using the Fridericia method and the resulting QTcF should be used for 
decision making and reporting. If QTcF exceeds 450 msec, or QRS exceeds 
120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF 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. 


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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. 
• Hemoglobin level 120 g/L (12.0 g/dL); 
• Platelet count 150 × 109/L (150,000 cells/mm3); 
• WBC count of 3.0 × 109/L (3000 cells/mm3); 
• ANC 1500 cells/mm3; 
• ALC 800 cells/mm3; 
• eGFR 90 mL/min/1.73 m2 based on the CKD-EPI 2009 equation6; 
• In the opinion of the investigator or Pfizer (or designee), have any clinically 
significant laboratory abnormality that may affect participant’s safety or 
interpretation of study data. 
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 1 pint (500 mL) or 
more within 60 days prior to dosing. 
23. History of sensitivity to heparin or heparin -induced thrombocytopenia. 
24. Pregnant and/or breastfeeding females. 
25. Unwilling or unable to comply with the criteria in the Lifestyle Considerations 
section of this protocol. 


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


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instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant or partner. 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention/enrolled in the study. 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 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) 
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 
Study intervention will be provided 
in vials packaged in individual 
cartons. Each vial and carton will 


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labeled as required per country 
requirement. 
be labeled as required per country 
requirement. 
 
Participants will receive study intervention at approximately 0800 hours on Day 1 (plus or 
minus 2 hours). Study intervention does not require fasting, but it should be noted that the 
safety laboratory test at Day -1 prior to the study intervention need a fast of at least 4 hours. 
Investigator site personnel will administer study intervention as a 60-minute intravenous 
infusion 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 drug 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 drug 
administration should be discontinued immediately and permanently. 
• If a participant experiences symptoms typical of infusion related reactions 
(eg, lightheadedness, nausea, chills, fever), the study drug 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 drug administration should be discontinued immediately and 
permanently. 
• In the event that there is an infusion interruption, the entire duration of drug 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. 


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3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual. 
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 investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record. 
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. 


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6.3. Measures to Minimize Bias: Randomization and Blinding 
6.3.1. Allocation to Study Intervention 
Participants will be allocated manually and randomly assigned to receive study intervention 
from a central randomization scheme. Investigators will remain blinded to each participant’s 
assigned study intervention throughout the course of the study. In order to maintain this 
blind, an otherwise uninvolved third party (for example, pharmacist) will be responsible for 
the preparation and dispensing of all study intervention according to the randomization 
schedule and assigned treatment for the individual participant. 
6.3.2. Breaking the Blind 
The method for breaking the blind in this study will be manual. A sealed envelope that 
contains the study intervention assignment(s) for each participant will be provided to the 
investigator. The sealed envelope will be retained by the investigator (or representative) in a 
secured area. In case of an emergency, the investigator has the sole responsibility for 
determining if unblinding of a participant’s treatment assignment is warranted. Participant 
safety must always be the first consideration in making such a determination. If the 
investigator decides that unblinding is warranted, the investigator should make every effort to 
contact the sponsor prior to unblinding a participant’s treatment assignment unless this could 
delay further management of the participant. If a participant’s treatment assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. When the 
blinding code is broken, the reason must be fully documented and entered on the CRF. 
Once the study is complete, all envelopes (sealed and opened) must be inventoried and 
retained until authorization for destruction has been provided. 
This is an investigator- and participant-blind (sponsor open) placebo-controlled study. Blood 
specimens will be obtained from all participants for PK analysis to maintain the study blind 
at the investigator site. Only the investigator site staff and blinded study monitor, if assigned, 
will be blinded to study treatment. 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. 


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The site will complete the required dosage Preparation Record located in the IP manual. The 
use of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee. 
6.5. 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. 


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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. 
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. 


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If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 
Lack of completion of all or any of the withdrawal/ET procedures will not be viewed as 
protocol deviations so long as the participant’s safety was preserved. 
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
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; 


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• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
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, but some laboratory items may need to be 
retested if the screening period exceeds more than 30 days. 
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, but some 
laboratory items may need to be retested if previous results are more than 30 days ago. 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. 


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The PK results that could unblind the study will not be reported to investigative sites or other 
blinded personnel until the study has been unblinded. 
If an IV catheter is utilized for blood sample collections, ECGs and vital sign assessments 
(pulse rate and BP) should be collected prior to the insertion of the catheter. 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 
The total blood sampling volume for individual participants in this study is approximately 
335 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. 
To prepare for study participation, participants will be instructed on the information in the 
Lifestyle Considerations and Concomitant Therapy sections of the protocol. 
8.1. Efficacy Assessments 
Not applicable. 
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues. 
8.2.1. Physical Examinations 
A complete physical examination will include, at a minimum, head, ears, eyes, nose, mouth, 
skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and 
neurological systems. 
A brief physical examination will include, at a minimum, assessments of general appearance, 
the respiratory and cardiovascular systems, and participant-reported symptoms. 
Physical examinations may be conducted by a physician. 
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 


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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 at other times 
specified in the SoA 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. Additional chest X-ray will be performed based 
on clinical needs when AEs occur. 
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 
from the arm with an intravenous infusion. Participants should be instructed not to speak 
during measurements. 
The same properly sized and calibrated BP cuff will be used to measure BP each time. The 
use of an automated device for measuring BP and pulse rate is acceptable; however, when 
done manually, pulse rate will be measured in the brachial/radial artery for at least 
30 seconds. When the timing of these measurements coincides with a blood collection, BP 
and pulse rate should be obtained prior to the nominal time of the blood collection. 
Additional collection times, or changes to collection times, of BP and pulse rate will be 
permitted, as necessary, to ensure appropriate collection of safety data. 
8.2.3.1. Temperature 
Temperature will be measured per local practice. The method chosen by the CRU should be 
used consistently throughout the study. 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 heart rate 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 5 minutes in a supine position. 


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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 post 
dose QTcF interval is increased by ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QT 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 post dose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QT value is ≥500 msec for any scheduled ECG for greater than 4 hours or at the 
discretion of the investigator (or sooner, at the discretion of the investigator); or c) QTcF 
intervals get progressively longer, the participant should undergo continuous ECG 
monitoring. A cardiologist should be consulted if QTcF 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 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range. 
ECG values of potential clinical concern are listed in Appendix 6. 
8.2.5. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition. 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within Day 157 (±3 days) after the last dose of study 
intervention should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 


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If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury. 
All protocol required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA. 
If laboratory values from non protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the source data, and in the CRF AE narrative. 
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. 


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8.2.5.1. 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. 
• 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 is tested viral load positive for HBV at screening will be excluded from 
the study. If there is any positive for viral load of HBV after screening, the participant should 
be discontinued from study treatment and referred to a hepatologist/specialist caring for HBV 
infection for appropriate evaluation and treatment. 
8.2.6. Tuberculosis Test 
Participants should be screened for TB using an IGRA per local guidelines. 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-GIT) test, T-SPOT®TB test, 
QuantiFERON-TB Gold test (QFT-G) or QuantiFERON-TB Gold Plus test (QFT-G 
Plus).. If T-SPOT test was completed within 12 weeks prior to Day 1, this is acceptable, 
however this test type cannot be offered for participants requiring the test during screening. If 
at any time the participant has signs or symptoms associated with TB, additional TB testing 
will be performed. 


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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. 
• 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. 
8.2.7. 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, a blood sample for viral surveillance sample may also be 
taken at the time of an AE, as clinically appropriate. 
8.2.8. COVID-19 Specific Assessments 
Participants will be tested for SARS-COVID-19 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 
a central or local laboratory. 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. 
8.2.9. 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 


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prior 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. 
8.2.10. Infusion Site Assessment 
Infusion site reactions will be assessed according to the SoA. Infusion site reactions may 
include but are not limited to: erythema, induration, ecchymosis, pain, and pruritus. 
Any signs or symptoms related to either an infusion site reaction should be treated according 
to the investigator’s standard of care and reported as adverse events. 
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 157 calendar days (±3 days) after the last administration of the study 
intervention. 
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator. 


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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 
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. 
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). 


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In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3. 
8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities 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. 


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• 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, inhalation or skin 
contact. 
• A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation or skin contact then exposes his female 
partner prior to or around the time of conception. 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
• If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until 157 days 
(±3 days) after last dose. 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file. 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
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). 


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


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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 
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. 
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 


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CCI 
Medication errors include: 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
In the event of a medication dosing error, the sponsor should be notified within 24 hours. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
8.4. Pharmacokinetics 
Blood samples of approximately 3 mL, to provide a minimum of 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 data collection tool (eg, CRF). Collection of samples more than 
10 hours after dose administration that are obtained ≤1 hour away from the nominal time 
relative to dosing will not be captured as a protocol deviation, as long as the exact time of the 
collection is noted on the source document and the data collection tool (eg, CRF). This 
protocol deviation window does not apply to samples to be collected more than 10 hours 
after dose administration at outpatient/follow-up visits with visit windows. 
Samples will be 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, or for other internal CCI 
 purposes. 
 


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CCI 
Samples collected for measurement of serum concentrations of PF-06823859 will be 
analyzed using a validated analytical method in compliance with applicable SOPs. 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case by case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. 
Drug concentration information that may 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. 
8.5. Genetics 
Genetics (specified analyses) are not evaluated in this study. 
8.6. Biomarkers 
Biomarkers are not evaluated in this study. 
8.7. Immunogenicity Assessments 
Blood samples of approximately 6 mL, to provide a minimum of 2 mL of 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 will be analyzed using a validated analytical method in compliance with applicable 
SOPs. Samples determined to be positive for ADA may be further characterized for NAb. 
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (eg, sample collection and processing steps, 


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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 may 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 
Not applicable. 
9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
 
Participant Analysis 
Set 
Description 
Safety Analysis Set 
All randomized participants who received at least 1 dose of 
the study intervention 
PK Concentration Set 
All randomized participants who received at least 1 dose of 
study intervention and at least 1 concentration value is 
reported 
PK Parameter Set 
All randomized participants who received at least 1 dose of 
study intervention and at least 1 of the PK parameters is 
calculated 
Immunogenicity 
Analysis Set 
All randomized participants who received at least 1 dose of 
study intervention with at least 1 post-treatment anti-drug 
antibody determination 


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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 endpoints. 
9.3.1. General Considerations 
No formal statistical tests will be performed. Descriptive summaries will be provided for all 
endpoints by treatment group. 
9.3.2. Pharmacokinetic Analyses of PF-06823859 
The PK parameters for PF-06823859 following single dose administration will be derived 
from the concentration-time profiles by noncompartmental analysis as detailed in Table 1. 
Actual PK sampling times will be used in the derivation of PK parameters. In the case that 
actual PK sampling times are not available, nominal PK sampling times will be used in the 
derivation of PK parameters. 
 
Table 1.  Definition of Serum PK Parameters for PF-06823859 
 
Parameter 
Definition 
Method of determination 
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 
AUCinfa 
Area under the serum concentration- 
time profile from time zero 
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) a 
Dose normalized AUCinf 
AUCinf /Dose 
AUClast 
Area under the serum concentration- 
time profile from time zero to the time 
of the last quantifiable concentration 
(Clast) 
Linear/Log trapezoidal method 
AUClast (dn) 
Dose normalized AUClast 
AUClast/Dose 
AUC14day 
Area under the concentration-time 
profile from time zero to 14 days post- 
dose (336 hours) 
Linear/Log trapezoidal method 
AUC28day 
Area under the concentration-time 
profile from time zero to 28 days post- 
dose (672 hours) 
Linear/Log trapezoidal method 
t½a 
Terminal half-life 
Loge(2)/kel, where kel is the terminal 
phase rate constant calculated by a 
linear regression of the log-linear 
concentration-time curve 
CLa 
Clearance 
Dose/AUCinf 
Vz 
Volume of distribution 
Dose/(AUCinf*kel) 


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Table 1. 
Definition of Serum PK Parameters for PF-06823859 
 
Parameter 
Definition 
Method of determination 
MRTa 
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 
 
The serum PK parameters for PF-06823859 will be summarized descriptively by treatment 
group, as applicable. Serum concentration of PF-06823859 will be summarized descriptively 
and plotted by study day. 
9.3.3. 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 
All safety analyses will be performed on the safety set. 
AEs, ECGs, vital signs, and safety laboratory data will be reviewed on an ongoing basis 
during the study to evaluate the safety of participants. Any clinical laboratory, ECG, vital 
sign abnormalities of potential clinical concern will be described. Safety data will be 
presented in tabular and/or graphical format and summarized descriptively, where 
appropriate. 
Incidence of viral infections or change in baseline of viral loads (CMV, VZV, EBV, HHV6, 
and HSV-1/2) if they occur, will be summarized by treatment group. 
Medical history and physical examination information, as applicable, collected during the 
course of the study will be considered source data and will not be required to be reported, 
unless otherwise noted. However, any untoward findings identified on physical examinations 
conducted during the active collection period will be captured as 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. 
9.3.4.1. Electrocardiogram Analyses 
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time. 


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The number (%) of participants with maximum post dose 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 
 
9.4. Interim Analyses 
No formal interim analysis will be conducted for this study. As this is an 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, agency communication, 
and/or supporting clinical development. 
9.5. Sample Size Determination 
The total sample size of approximately 12 participants (10 active, 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. 
If more than 2 participants discontinue or withdraw before completing at least the follow-up 
visit at Day 100, or if there are participants whose PK samples are considered to be non- 
evaluable with respect to the primary PK objective, additional participants may be enrolled 
upon alignment between the sponsor and the investigator such that approximate 
10 participants could provide evaluable PK samples for no less than Day 100 follow-up visit. 


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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 investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to implementation 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 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 


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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of. 
10.1.2. Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant or his/her legally authorized representative and answer 
all questions regarding the study. The participant or his/her legally authorized representative 
should be given sufficient time and opportunity to ask questions and to decide whether or not 
to participate in the trial. 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data 
protection requirements, where applicable, and the IRB/EC or study center. 
The investigator must ensure that each study participant or his or her legally authorized 
representative is fully informed about the nature and objectives of the study, the sharing of 
data related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
The participant or his or her legally authorized representative 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 or his or her 
legally authorized representative. 
The participant or his or her legally authorized representative must be informed that his/her 
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities. 
The investigator further must ensure that each study participant or his or her legally 
authorized representative is fully informed about his or her right to access and correct his or 
her personal data and to withdraw consent for the processing of his or her personal data. 


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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 or his or her legally authorized representative must be reconsented to the most 
current version of the ICD(s) during their participation in the study. 
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICD. 
10.1.4. Data Protection 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data. 
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password-protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law. 
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record 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. 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
This study will not use a DMC. 
10.1.6. 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. 


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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. 
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 


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be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
10.1.7. 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. 
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 for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained. 
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems. 
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 


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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. 
10.1.8. Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site. 
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in source data 
agreement, 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. 
10.1.9. 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. 


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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. 
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. 
10.1.10. 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. 


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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. 
10.1.11. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the Investigator Site Master File. 
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
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 2. 
Protocol-Required Safety Laboratory Assessments 
 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit 
RBC count 
MCV 
MCH 
MCHC 
Platelet count 
WBC count 
Total neutrophils 
(Abs) 
Eosinophils (Abs) 
Monocytes (Abs) 
Basophils (Abs) 
Lymphocytes (Abs) 
BUN/urea and creatinine 
Glucose (fasting) 
Calcium 
Sodium 
Potassium 
Chloride 
Total CO2 (bicarbonate) 
AST, ALT 
Total bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
Local Dipstick: 
pH 
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites 
Leukocyte 
esterase/WBC 
Laboratory: 
Microscopy and 
Culturea 
As per SoA: 
• 
COVID-19 testing 
• 
Pregnancy test (b-hCG)b 
• 
Urine drug screeningc 
• 
Viral surveillance: 
CMV, VZV, EBV, 
HHV6, HSV-1/2 
• 
PT 
• 
INR 
• 
aPTT 
• 
HBV DNAd, if 
applicable 
At screening only: 
• 
FSHe 
• 
HIV 
• 
HBsAg 
• 
HBsAb 
• 
HBcAb 
• 
HCVAb 
• 
syphilis 
a. 
Urine Micorspocy was routinely done in site. Urine or blood Culture will be done under investigator’s 
judgement. 
b. 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. 
c. 
The minimum requirement for drug screening includes cocaine, THC, opiates/opioids, 
benzodiazepines, and amphetamines (others are site and study specific). 
d. HBV DNA testing will be performed according to Section 8.2.5.1. 
e. 
For confirmation of postmenopausal status only. 
 
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) 
nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 


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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. 
* 
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. 
• The investigator will then record all relevant AE or SAE information in the CRF. 
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 
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)* 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF. 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE). ** 
Environmental or 
None. Exposure to a study 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.*** 
occupational exposure 
non-participant is not 
to the product under 
collected on the CRF. 
study to a non- 
participant (not 
involving EDP or EDB). 


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• 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 157 days after the last dose of study intervention, 
which corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s) (eg, 5 terminal half-lives): 
o Refrain from donating sperm. 
PLUS either: 
o Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent; 
OR 
o Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person. 
• In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4). 
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: 
o Is not a WOCBP (see definitions below in Section 10.4.3). 
OR 
o 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 157 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) (5 terminal half-lives). The investigator should 
evaluate the effectiveness of the contraceptive method in relationship to the first dose 
of study intervention. 
o 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 157 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) (5 terminal half-lives). In addition, a second effective method of 
contraception, as described below, must be used. The investigator should evaluate the 


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effectiveness of the contraceptive method in relationship to the first dose of study 
intervention. 
A WOCBP agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during 
this period. 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. 


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• 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 
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; 
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). 


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10.5. Appendix 5: 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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10.6. Appendix 6: ECG Findings of Potential Clinical Concern 
 
ECG Findings That May Qualify as AEs 
• Marked sinus bradycardia (rate <40 bpm) lasting minutes. 
• New PR interval prolongation >280 msec. 
• New prolongation of QTcF to >480 msec (absolute) or by 60 msec from 
baseline. 
• New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, 
rate <120 bpm. 
• New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ 
duration. 
• Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive 
ventricular complexes. 
ECG Findings That May Qualify as SAEs 
• QTcF prolongation >500 msec. 
• New ST-T changes suggestive of myocardial ischemia. 
• New-onset left bundle branch block (QRS >120 msec). 
• New-onset right bundle branch block (QRS >120 msec). 
• Symptomatic bradycardia. 
• Asystole: 
• In awake, symptom-free participants in sinus rhythm, with documented 
periods of asystole ≥3.0 seconds or any escape rate <40 bpm, or with an 
escape rhythm that is below the AV node. 
• In awake, symptom-free participants with atrial fibrillation and bradycardia 
with 1 or more pauses of at least 5 seconds or longer. 
• Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm. 
• Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute). 


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


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10.7. Appendix 7: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
Abs 
absolute 
ADA 
antidrug antibodies 
ADL 
activities of daily living 
AE 
adverse event 
ALC 
absolute lymphocyte count 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
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 
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 
AUMCinf 
area under the moment curve from time 0 extrapolated to infinity 
AV 
atrioventricular 
BCG 
Bacillus Calmette-Guérin 
-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 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL 
clearance 
Cmax 
maximum observed concentration 
CMV 
cytomegalovirus 
CO2 
carbon dioxide 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
CRU 
clinical research unit 
CSR 
clinical study report 
CT 
clinical trial; computed tomography 


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Abbreviation 
Term 
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 
DOF 
duration of the IV infusion 
DU 
dispensable unit 
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 
eGFR 
estimated glomerular filtration rate 
EMA 
European Medicines Agency 
ePPND 
enhanced pre and postnatal development 
ET 
early termination 
EU 
European Union 
EudraCT 
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 
HBV DNA 
hepatitis B virus DNA 
HCVAb 
hepatitis C antibody 
HHV6 
Human Herpes Virus 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 


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Abbreviation 
Term 
IFN 
interferon 
IFN- 
interferon- 
IFN- 
interferon- 
IFNAR 
interferon-a/b 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 
IPAL 
Investigational Product Accountability Log 
IRB 
institutional review board 
ISR 
injection site reaction 
IV 
intravenous 
JAK 
Janus kinase 
kel 
terminal phase rate constant 
LBBB 
left bundle branch block 
LFT 
liver function test 
Loge 
natural logarithm 
mAb 
monoclonal antibody 
MAD 
multiple ascending dose 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MDR 
medical device regulation 
MRI 
magnetic resonance imaging 
MRT 
mean residence time 
N/A 
not applicable 
NAb 
neutralizing antibodies 
NIMP 
noninvestigational medicinal product 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PI 
principal investigator 
PK 
pharmacokinetic(s) 
PPD 
purified protein derivative 
PR 
pulse rate 
PT 
prothrombin time 
PVC 
premature ventricular contraction/complex 
Q2W 
once every 2 weeks 
Q4W 
once every 4 weeks 
QFT-GIT 
QuantiFERON®-TB Gold In Tube 


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Abbreviation 
Term 
QTc 
corrected QT 
QTcF 
corrected QT (Fridericia method) 
qual 
qualitative 
Rac, AUCτ 
accumulation ratio for AUCτ 
Rac, Cmax 
accumulation ratio for Cmax 
RBC 
red blood cell 
SAD 
single ascending dose 
SADE 
serious adverse device effect 
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 
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 
Vz 
volume at distribution 
VZV 
varicella-zoster virus 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential 


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11. REFERENCES 
 
 
1 
National Organization of Rare Disease, NORD 2015.Available from: 
http://rarediseases.org/rare-diseases/dermatomyositis/. Accessed: 16 June 2021. 
2 
Myositis Support and Understanding Association Inc. 2010-2017. Available from: 
https://understandingmyositis.org/types-of-myositis/dermatomyositis/?gclid=CIXP- 
fLSns8CFYM9gQodSZIDlA. Accessed: 16 June 2021. 
3 
Fasano S, Alves SC, Isenberg DA. Current pharmacological treatment of idiopathic 
inflammatory myopathies. Expert Rev Clin Pharmacol. 2015. DOI: 
10.1586/17512433.2016.1136561. 
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. 
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 
Levey AS, Stevens LA, Schmid CH, et al. CKD-EPI . A new equation to estimate 
glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12. DOI: 10.7326/0003- 
4819-150-9-200905050-00006. Erratum in: Ann Intern Med. 2011 ;155(6):408. PMID: 
19414839; PMCID: PMC2763564. 

SAP_001.pdf: 
  
Protocol C0251007 (PF-06823859) Statistical Analysis Plan Amendment 1 
 
PFIZER CONFIDENTIAL 
 
The official version of this form is located in the electronic document management system. 
 
Page 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol C0251007 
 
 
 
 
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, 
PLACEBO-CONTROLLED, STUDY TO EVALUATE THE PHARMACOKINETICS, 
SAFETY, AND TOLERABILITY FOLLOWING A SINGLE DOSE OF PF-06823859 
IN HEALTHY CHINESE PARTICIPANTS 
 
 
 
Statistical Analysis Plan  
(SAP) 
 
 
 
 
 
 
 
Version: 
2 
 
Date:  
9 Jun 2022   


  
Protocol C0251007 (PF-06823859) Statistical Analysis Plan Amendment 1 
 
PFIZER CONFIDENTIAL 
 
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Page 2 
TABLE OF CONTENTS 
LIST OF TABLES .....................................................................................................................4 
APPENDICES ...........................................................................................................................4 
1. VERSION HISTORY ............................................................................................................5 
2. INTRODUCTION .................................................................................................................5 
2.1. Study Objectives, Endpoints, and Estimands ............................................................6 
2.2. Study Design .............................................................................................................6 
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7 
3.1. Primary Endpoint(s) ..................................................................................................7 
3.2. Secondary Endpoint(s) ..............................................................................................7 
3.3. Other Endpoint(s) ......................................................................................................7 
3.4. Baseline Variables .....................................................................................................8 
3.5. Safety Endpoints .......................................................................................................8 
3.5.1. Adverse Events .............................................................................................8 
3.5.2. Laboratory Data ............................................................................................8 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) .....................................................8 
5. GENERAL METHODOLOGY AND CONVENTIONS ......................................................8 
5.1. Hypotheses and Decision Rules ................................................................................8 
5.2. General Methods .......................................................................................................9 
5.2.1. Analyses for Binary Endpoints .....................................................................9 
5.2.2. Analyses for Continuous Endpoints .............................................................9 
5.2.3. Analyses for Categorical Endpoints .............................................................9 
5.2.4. Analyses for Time-to-Event Endpoints ........................................................9 
5.3. Methods to Manage Missing Data ............................................................................9 
5.3.1. Pharmacokinetic Concentrations ..................................................................9 
5.3.2. Pharmacokinetic Parameters .......................................................................10 
6. ANALYSES AND SUMMARIES ......................................................................................10 
6.1. Pharmacokinetic Analysis .......................................................................................10 
6.1.1. Pharmacokinetic Parameters .......................................................................10 
6.1.2. Pharmacokinetic Concentrations ................................................................11 


  
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6.2. Immunogenicity Analysis .......................................................................................12 
6.3. Subset Analyses .......................................................................................................12 
6.4. Baseline and Other Summaries and Analyses .........................................................12 
6.4.1. Baseline Summaries ....................................................................................12 
6.4.2. Study Conduct and Participant Disposition ................................................12 
6.5. Safety Summaries and Analyses .............................................................................13 
6.5.1. Adverse Events ...........................................................................................13 
6.5.2. Laboratory Data ..........................................................................................13 
6.5.3. Vital Signs ..................................................................................................13 
6.5.4. Electrocardiograms .....................................................................................13 
6.5.5. Other Safety Data .......................................................................................14 
7. INTERIM ANALYSES .......................................................................................................14 
8. REFERENCES ....................................................................................................................14 
9. APPENDICES .....................................................................................................................15 
 
 
 


  
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LIST OF TABLES 
Table 1. 
Summary of Changes ..................................................................................5 
 
APPENDICES 
Appendix 1. List of Abbreviations...........................................................................................15 
 
 
 


  
Protocol C0251007 (PF-06823859) Statistical Analysis Plan Amendment 1 
 
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1. VERSION HISTORY 
Table 1. 
Summary of Changes 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Rationale 
Specific Changes 
1 
16 Aug 2021 
Original 
25 Jun 2021 
N/A 
N/A 
2 
9 Jun 2022 
Amendment 
1 10 May 
2022 
To allow 
additional 
participants to 
be enrolled in 
the study in the 
event of 
participants’ PK 
samples are 
considered to be 
non-evaluable 
with respect to 
the primary PK 
objective. 
Section 2.2  
The following statement was updated:  
 
Original statement: 
If more than 2 participants discontinue or 
withdraw before completing at least the 
follow-up visit at Day 100, participants may 
be replaced at the discretion of the 
investigator upon alignment with the 
sponsor. 
Updated statement: 
If more than 2 participants discontinue or 
withdraw before completing at least the 
follow-up visit at Day 100, or if there are 
participants whose PK samples are 
considered to be non-evaluable with respect 
to the primary PK objective, additional 
participants may be enrolled upon 
alignment between the sponsor and the 
investigator such that approximate 
10 participants could provide evaluable PK 
samples for no less than Day 100 follow-up 
visit. For participants whose PK samples are 
considered to be non-evaluable with respect 
to the primary PK objective, their PK 
sample collection will stop for ethic 
consideration.
 
2. INTRODUCTION 
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C0251007.  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. 


  
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The purpose of this study is to evaluate the single-dose PK, safety, and tolerability of 
PF-06823859 after single IV administration to healthy adult Chinese participants. The 
information of PK, safety, and tolerability in healthy Chinese participants is being collected 
to support future PF-06823859 clinical development as well as drug registration in China.  
2.1. Study Objectives, Endpoints, and Estimands 
The followings are objectives and endpoints in this study. Estimands framework does not 
apply to this phase I study. 
Objectives 
Endpoints 
Primary: 
Primary:  
 To evaluate the PK profile of single IV 
dose of 900 mg PF-06823859 in 
healthy Chinese participants.  
 To determine the safety and tolerability 
of single IV dose of 900 mg 
PF-06823859 in healthy Chinese 
participants. 
 Serum PF-06823859 primary PK 
parameters, as permitted by data: Cmax, 
Tmax, AUC14day, AUC28day, AUCinf, and 
t½, 
 Assessments of AEs/SAEs including 
infusion site reactions and viral 
infections, vital signs, ECGs and 
laboratory tests. 
Secondary:  
Secondary:  
 To further evaluate the PK of 
PF-06823859. 
 To evaluate the immunogenicity of 
PF-06823859. 
 
 Serum PF-06823859 PK parameters, as 
permitted by data: Cmax (dn), AUClast, 
AUClast (dn), AUCinf (dn), CL, Vz, and 
MRT. 
 Incidence of the development of ADA 
and Nab. 
 
2.2. Study Design 
This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study to 
evaluate the PK, safety, and tolerability following a single dose of PF-06823859 (900 mg) in 
healthy Chinese participants. 
Approximately 12 participants will be enrolled into the study. Approximately 10 participants 
will be randomized to PF-06823859 and approximately 2 participants will be randomized to 
placebo. 


  
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If more than 2 participants discontinue or withdraw before completing at least the follow-up 
visit at Day 100, or if there are participants whose PK samples are considered to be non-
evaluable with respect to the primary PK objective, additional participants may be enrolled 
upon alignment between the sponsor and the investigator such that approximate 
10 participants could provide evaluable PK samples for no less than Day 100 follow-up visit. 
For participants whose PK samples are considered to be non-evaluable with respect to the 
primary PK objective, their PK sample collection will be stopped for ethic consideration.  
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. 
Participants will be admitted into the CRU approximately 1 day prior to dosing and are 
required to remain in the CRU through completion of Day 5 evaluations. Participants will 
return to the CRU for outpatient follow-up visits through Day 157. 
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. 
No formal interim analysis will be conducted for this study. As this is a sponsor-open study, 
the sponsor will conduct unblinded reviews of the safety, PK, and immunogenicity data 
through Day 28 after treatment administration to preliminarily assess any ethnic differences 
between Chinese and non-Chinese to support China joining future global PF-06823859 
clinical development.  
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS 
3.1. Primary Endpoint(s) 
 Serum PF-06823859 primary PK parameters, as permitted by data: Cmax, Tmax, AUC14day, 
AUC28day, AUCinf, and t½, 
 Assessments of AEs/SAEs including infusion site reactions and viral infections, vital 
signs, ECGs and laboratory tests. 
3.2. Secondary Endpoint(s) 
 Serum PF-06823859 PK parameters, as permitted by data: Cmax (dn), AUClast, 
AUClast (dn), AUCinf (dn), CL, Vz, and MRT. 
 Incidence of the development of ADA and Nab. 
3.3. Other Endpoint(s) 
Not applicable. 


  
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3.4. Baseline Variables 
The baseline value for laboratory, 12-Lead ECG and vital signs is defined as the latest 
measurement prior to taking dose.  
3.5. Safety Endpoints 
3.5.1. Adverse Events 
Any events occurring following start of treatment will be counted as treatment emergent.  
3.5.2. Laboratory Data 
Safety laboratory tests will be performed as described in the protocol. 
 
To determine if there are any clinically significant laboratory abnormalities, the 
hematological, clinical chemistry (serum) and urinalysis safety tests will be assessed against 
the criteria specified in the sponsor reporting standards. The assessment will not take into 
account whether each subject’s baseline test result is within or outside the laboratory 
reference range for the particular laboratory parameter.  
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) 
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures. 
Participant Analysis Set 
Description 
Safety Analysis Set 
All randomized participants who received at least 1 dose of the 
study intervention 
PK Concentration Set 
All randomized participants who received at least 1 dose of 
study intervention and at least 1 concentration value is reported 
PK Parameter Set 
All randomized participants who received at least 1 dose of 
study intervention and at least 1 of the PK parameters is 
calculated 
Immunogenicity Analysis 
Set 
All randomized participants who received at least 1 dose of 
study intervention with at least 1 post-treatment anti-drug 
antibody determination 
5. GENERAL METHODOLOGY AND CONVENTIONS 
5.1. Hypotheses and Decision Rules 
There are no stasistical hypotheses for this study. 


  
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5.2. General Methods 
No formal statistical tests will be performed. Descriptive summaries will be provided for all 
endpoints by treatment group. 
5.2.1. Analyses for Binary Endpoints 
Not applicable. 
5.2.2. Analyses for Continuous Endpoints 
Not applicable. 
5.2.3. Analyses for Categorical Endpoints 
Not applicable. 
5.2.4. Analyses for Time-to-Event Endpoints 
Not applicable. 
5.3. Methods to Manage Missing Data 
5.3.1. Pharmacokinetic Concentrations  
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 the listings BLQ values will be reported as “<LLQ”, where 
lower limit of quantification (LLQ) will be replaced with the value for the lower limit of 
quantification. 
Deviations, missing concentrations and anomalous values 
Subjects who experience events that may affect their PK profile (eg, due to known loss of 
drug during IV administration ) may be excluded from the PK analysis. 
 
In summary tables and plots of mean and median profiles of PK, statistics will be calculated 
having setting concentrations to missing if one of the following cases is true: 
 
1. A concentration has been collected as ND (ie, not done) or NS (ie, no sample); 
 
2. A deviation in sampling time is of sufficient concern or a concentration has been flagged 
anomalous by the PK analyst. 
 
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing. 


  
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5.3.2. Pharmacokinetic Parameters  
Actual PK sampling times will be used in the derivation of PK parameters. 
 
If a PK parameter cannot be derived from a subject’s concentration data, the parameter will 
be coded as NC (ie, not calculated). (Note that NC values will not be generated beyond the 
day that a subject discontinues). 
 
In summary tables, statistics will be calculated by setting NC values to missing; and statistics 
will not be presented if more than 50% of the data are NC. 
 
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as incomplete SC injection), this will be footnoted in summary 
tables and will not be included in the calculation of summary statistics or statistical analyses. 
6. ANALYSES AND SUMMARIES 
6.1. Pharmacokinetic Analysis 
6.1.1. Pharmacokinetic Parameters 
The PK parameters for PF-06823859 following single dose administration will be derived 
from the concentration-time profiles by noncompartmental analysis and summarized 
descriptively.  
The PK parameter analysis will be carried out with PK parameter analysis set. 
Calculation of PK parameters 
Parameter 
Definition 
Method of determination 
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 
AUCinfa 
Area under the serum concentration-
time profile from time zero 
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) a 
Dose normalized AUCinf
AUCinf /Dose 
AUClast 
Area under the serum concentration-
time profile from time zero to the time 
of the last quantifiable concentration 
(Clast) 
Linear/Log trapezoidal method 
AUClast (dn) 
Dose normalized AUClast 
AUClast/Dose 
AUC14day 
Area under the concentration-time 
profile from time zero to 14 days post-
dose (336 hours)
Linear/Log trapezoidal method 


  
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Parameter 
Definition 
Method of determination 
AUC28day 
Area under the concentration-time 
profile from time zero to 28 days post-
dose (672 hours)
Linear/Log trapezoidal method 
t½a 
Terminal half-life 
Loge(2)/kel, where kel is the terminal 
phase rate constant calculated by a 
linear regression of the log-linear 
concentration-time curve 
CLa 
Clearance
Dose/AUCinf 
Vz 
Volume of distribution  
Dose/(AUCinf*kel) 
MRTa 
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 
 
Actual PK sampling times will be used in the derivation of PK parameters. In the case that 
actual PK sampling times are not available, nominal PK sampling times will be used in the 
derivation of PK parameters. 
Summary statsitics will be provided for these PK parameters as summarized below: 
Parameter 
Summary statistics 
AUClast, AUClast(dn), AUCinf, 
AUCinf(dn), AUC14day, AUC28day, 
Cmax, Cmax(dn), CL, Vz, MRT
N, arithmetic mean, median, coefficient of variation 
(CV)%, standard deviation (SD), minimum, maximum, 
geometric mean and geometric CV%. 
Tmax 
N, median, minimum, maximum.
t1/2 
N, arithmetic mean, median, CV%, SD, minimum, 
Maximum.
 
Box and whisker plots for individual subject parameters (AUClast, AUClast(dn), AUCinf , 
AUCinf(dn), AUC14day, AUC28day, Cmax and Cmax(dn)) will be presented and overlaid with 
geometric means. 
 
6.1.2. Pharmacokinetic Concentrations 
Presentations for PF-06823859 concentrations will include: 
 a listing of all concentrations sorted by subject ID and nominal time postdose. The 
concentration listing will also include the actual times. Deviations from the nominal 
time will be given in a separate lsiting. 
 a summary of concentrations by nominal time postdose, where the set of statistics will 
include n, mean, median, SD, CV, minimum, maximum and the number of 
concentations above the LLQ. 


  
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 Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose. 
 Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose. 
 Individual concentrations time plots (on both linear and semi-log scales) against 
actual time postdose. 
 Individual concentrations time plots by participant (on both linear and semi-log 
scales) agains actual time postdose (there will be separate plots for each participant 
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. 
 
These analyses will be carried out with PK concentration analysis set. 
6.2. Immunogenicity Analysis 
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. 
6.3. Subset Analyses 
Not applicable. 
6.4. Baseline and Other Summaries and Analyses 
6.4.1. Baseline Summaries 
Demographic and baseline characeteristics will be summarized descriptively. 
6.4.2. Study Conduct and Participant Disposition 
A subject disposition table will be provided. Subject disposition will be summarized and will 
include the number and percentage of participants randomized, treated, completing and 
discontinuing from the study, the number of participants in each analysis population and 
reasons for discontinuation of study. The percentages will use the number of randomized as 
the denominator. 


  
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6.5. Safety Summaries and Analyses 
6.5.1. Adverse Events 
Adverse events will be reported in accordance with the sponsor reporting standards. Adverse 
events related to COVID-19 will be summarized. 
6.5.2. Laboratory Data 
Laboratory data will be summarized using Pfizer’s implementation of CDISC standards.  
Change from baseline will also be summarized by treatment and visit. 
Incidence of laboratory test abnormalities (without regard to baseline abnormality) will be 
summarized.  
6.5.3. Vital Signs 
Vital signs will be summarized using Pfizer’s implementation of CDISC standards. For each 
planned timepoint, absolute values and change from baseline values will be summarized with 
descriptive statistics.  
Maximum absolute values and maximum change from baseline for vital signs will also be 
summarized descriptively by treatment using categories. Numbers and percentages of 
participants meeting the categorical criteria will be provided by treatment and individual 
values listed. 
 
Categories for Vital Signs 
Systolic BP (mm Hg) 
min. <90
Systolic BP (mm Hg) 
change from baseline  
max. decrease ≥30 
max. increase ≥30 
Diastolic BP (mm Hg) 
min. <50
Diastolic BP (mm Hg) 
change from baseline 
max. decrease ≥20 
max. increase ≥20 
6.5.4. Electrocardiograms 
Baseline and changes from baseline for the ECG parameters heart rate, QT interval, QTc 
interval, PR interal and QRS interval will be summarized by treatment and time.  


  
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The number and percentages of participants with maximum postdose QTc values and 
maximum increases from baseline in the following categorie 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 
6.5.5. Other Safety Data 
Incidence of viral infections or change in baseline of viral loads (CMV, VZV, EBV, HHV6, 
and HSV-1/2) if they occur, will be summarized by treatment group. 
Medical history and physical examination information, as applicable, collected during the 
course of the study will be considered source data and will not be required to be reported, 
unless otherwise noted. However, any untoward findings identified on physical examinations 
conducted during the active collection period will be captured as AEs, if those findings meet 
the definition of an AE.  
All concomitant medications as well as non-drug treatments will be provided in the listings. 
The safety analyses will be analyzed using the safety analysis set. 
7. INTERIM ANALYSES 
No formal interim analysis will be conducted for this study.   
8. REFERENCES 
Not applicable.  


  
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9. APPENDICES 
Appendix 1. 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
AUCinf 
AUC from time 0 extrapolated to infinite time 
AUClast 
AUC from time 0 to the time of the last quantifiable concentration
AUMCinf  
area under the moment curve from time 0 extrapolated to infinity
BLQ 
Below the limit of quantification
BP 
blood pressure
bpm 
beats per minute
CL 
clearance
Cmax 
maximum observed concentration
CMV 
cytomegalovirus
COVID-19 
coronavirus disease 2019
CRU 
clinical research unit
dn 
dose normalized
DOF 
duration of the IV infusion
EBV 
Epstein Barr virus
ECG 
electrocardiogram
eCRF 
electronic case report form
HHV6 
Human Herpes Virus 6
HSV-1 
herpes simplex virus type 1
HSV-2 
herpes simplex virus type 2
ID 
identification
IV 
intravenous
kel 
terminal phase rate constant
LLQ 
lower limit of quantification
MRT 
mean residence time
N/A 
not applicable
NAb 
neutralizing antibodies
ND 
not done
NS 
no sample
PK 
pharmacokinetic(s)
PR 
pulse rate
QTc 
corrected QT
QTcF 
corrected QT (Fridericia method)


  
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Abbreviation 
Term 
SAE 
serious adverse event
SAP 
statistical analysis plan
SC 
subcutaneous(ly)
SoA 
schedule of activities
TEAE 
treatment emergent adverse event
t½ 
terminal phase half-life
Tmax 
time to reach Cmax
Vz 
volume at distribution
VZV 
varicella-zoster virus