A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA COMPARED TO LICENSED INACTIVATED INFLUENZA VACCINE IN HEALTHY ADULTS 18 YEARS OF AGE OR OLDER
Phase: PHASE3
Conditions: Influenza, Human
Sponsor: Pfizer

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 1
A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE 
EFFICACY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A 
MODIFIED RNA VACCINE AGAINST INFLUENZA COMPARED TO LICENSED 
INACTIVATED INFLUENZA VACCINE IN HEALTHY ADULTS 18 YEARS OF 
AGE OR OLDER
Study Intervention Number:
PF-07252220
Study Intervention Name:
Influenza modRNA Vaccine
US IND Number:
27600
EudraCT Number:
N/A
ClinicalTrials.gov ID:
NCT05540522
Pediatric Investigational Plan Number:
N/A
Protocol Number:
C4781004
Phase:
3
Brief Title: A Study to Evaluate the Efficacy, Safety, Tolerability, and Immunogenicity of 
a Modified RNA Vaccine Against Influenza in Adults 18 Years of Age or Older
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.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 4
2 7 J u ne 2 0 2 3
A me n d me nt 3
2 6 Marc h 2 0 2 3
A me n d me nt 2
0 9 N o ve m ber 2 0 2 2
A me n d me nt 1
2 8 J ul y  2 0 2 2
Ori gi nal pr ot oc ol
0 7 J u ne 2 0 2 2
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a nd I R Bs/ E Cs a n d a n y  pr ot oc ol a d mi nistrati ve c ha n ge 
letter(s).
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
A m e n d me nt 4 ( 2 7 J u ne 2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt :
I n res p o nse t o re g ulat or y a ge nc y fee d bac k, m o ve d i m m u n o ge nicity t o a sec o n dar y e n d p oi nt 
(fr o m e x pl orat or y) a n d i ncl u de d t he use of H AIs
t o q ua ntif y 
i m m u ne res p o nses.
Secti o n # a n d N a m e
Descri pti o n of C h a n ge
Brief R ati o n ale
S u bst a nti al or 
N o ns u bst a nti al
1. 1 S y n o psis
U p date d t o reflect t he 
e q ui vale nt re visi o ns i n 
t he b o d y of t he pr ot oc ol.
T o e ns ure t he la n g ua ge is 
c o nsiste nt wit h t he b o d y 
of t he pr ot oc ol.
S u bsta ntial .
2. 2. 3 N ucle osi de -M o difie d 
m R N A Vacci nes

C ha n ge d t he n u m ber 
of B N T 1 6 2 b 2 d oses 
a d mi nistere d t o t he 
n u m ber of 
B N T 1 6 2 b 2 d oses 
t hat ha ve bee n 
distri b ute d . 

U p date d t he 
i nci de nce of 
m y ocar ditis a fter
C O VI D -1 9 .
T o ali g n wit h t he 
e mer gi n g data a n d 
esta blis he d safet y pr ofile 
of t he C O VI D -1 9 
vacci ne .
S u bsta ntial.
2. 2. 5 Cli nical O ver vie w
A b bre viate d t he res ults
fr o m t he P hase 1/ 2 st u d y 
( C 4 7 8 1 0 0 1) a n d state d
t hat the preli mi nar y 
res ults ca n be f o u n d i n 
t he I B.
A d diti o nal g ui da nce t o 
t he i n vesti gat or relati n g 
t o w here t he latest 
i nfl ue nza vacci ne 
i m m u n o ge nicit y res ults 
ca n be f o u n d .
S u bsta ntial.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 6
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schema ....................................................................................................................30
1.3. Schedule of Activities .............................................................................................31
2. INTRODUCTION ...............................................................................................................34
2.1. Study Rationale .......................................................................................................34
2.2. Background .............................................................................................................34
2.2.1. Influenza .....................................................................................................34
2.2.2. Influenza Vaccination.................................................................................34
2.2.2.1. Assessing Influenza Vaccine Immunogenicity .........................35
2.2.3. Nucleoside-Modified mRNA Vaccines......................................................35
2.2.4. Potential for mRNA Influenza Vaccines ....................................................36
2.2.5. Clinical Overview.......................................................................................36
2.3. Benefit/Risk Assessment.........................................................................................37
2.3.1. Risk Assessment.........................................................................................39
2.3.2. Benefit Assessment.....................................................................................42
2.3.3. Overall Benefit/Risk Conclusion................................................................42
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................43
4. STUDY DESIGN.................................................................................................................52
4.1. Overall Design.........................................................................................................52
4.2. Scientific Rationale for Study Design.....................................................................54
4.2.1. Diversity of Study Population ....................................................................54
4.2.2. Choice of Contraception/Barrier Requirements .........................................54
4.3. Justification for Dose ..............................................................................................54
4.4. End of Study Definition ..........................................................................................54
5. STUDY POPULATION......................................................................................................55
5.1. Inclusion Criteria.....................................................................................................55
5.2. Exclusion Criteria....................................................................................................56
5.3. Lifestyle Considerations..........................................................................................57
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 7
5.3.1. Contraception..............................................................................................57
5.4. Screen Failures ........................................................................................................58
5.5. Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention...........................58
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................58
6.1. Study Intervention(s) Administered........................................................................58
6.1.1. Administration............................................................................................59
6.1.2. Medical Devices .........................................................................................60
6.2. Preparation, Handling, Storage, and Accountability...............................................60
6.2.1. Preparation and Dispensing........................................................................61
6.3. Assignment to Study Intervention...........................................................................61
6.4. Blinding...................................................................................................................61
6.4.1. Blinding of Participants..............................................................................61
6.4.2. Blinding of Site Personnel..........................................................................62
6.4.3. Blinding of the Sponsor..............................................................................62
6.4.4. Breaking the Blind......................................................................................63
6.5. Study Intervention Compliance...............................................................................63
6.6. Dose Modification...................................................................................................63
6.7. Continued Access to Study Intervention After the End of the Study......................63
6.8. Treatment of Overdose............................................................................................63
6.9. Prior and Concomitant Therapy ..............................................................................64
6.9.1. Prohibited During the Study.......................................................................64
6.9.2. Permitted During the Study ........................................................................65
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................65
7.1. Discontinuation of Study Intervention ....................................................................65
7.2. Participant Discontinuation/Withdrawal From the Study.......................................65
7.2.1. Withdrawal of Consent...............................................................................66
7.3. Lost to Follow-Up ...................................................................................................67
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................67
8.1. Administrative Procedures ......................................................................................67
8.1.1. Telehealth Visits.........................................................................................68
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 8
8.1.2. Home Health Visits.....................................................................................68
8.2. Efficacy and/or Immunogenicity Assessments .......................................................69
8.2.1. Surveillance for Influenza...........................................................................69
8.2.1.1. Antigenic Characterization of Influenza Viruses......................69
8.2.1.2. ILI Memory Aid........................................................................69
8.2.2. Immunogenicity Assessments ....................................................................70
8.2.3. Biological Samples.....................................................................................70
8.3. Safety Assessments .................................................................................................71
8.3.1. Physical Examinations................................................................................71
8.3.2. Vital Signs ..................................................................................................71
8.3.3. Clinical Safety Laboratory Assessments ....................................................71
8.3.4. Reactogenicity Electronic Diary (Reactogenicity Subset Participants 
Only) ................................................................................................................71
8.3.4.1. Grading Scales...........................................................................72
8.3.4.2. Local Reactions.........................................................................72
8.3.4.3. Systemic Events ........................................................................73
8.3.4.4. Fever..........................................................................................74
8.3.4.5. Antipyretic Medication .............................................................75
8.3.5. Pregnancy Testing ......................................................................................75
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................75
8.4.1. Time Period and Frequency for Collecting AE and SAE Information.......75
8.4.1.1. Reporting SAEs to Pfizer Safety...............................................76
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF...................77
8.4.2. Method of Detecting AEs and SAEs ..........................................................77
8.4.3. Follow-Up of AEs and SAEs......................................................................77
8.4.4. Regulatory Reporting Requirements for SAEs...........................................77
8.4.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................78
8.4.5.1. Exposure During Pregnancy......................................................78
8.4.5.2. Exposure During Breastfeeding ................................................80
8.4.5.3. Occupational Exposure .............................................................80
8.4.6. Cardiovascular and Death Events...............................................................80
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 9
8. 4. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif y i n g as A Es or S A Es ..............................................................................8 0
8. 4. 8. A d verse E ve nts of S pecial I nterest............................................................. 8 1
8. 4. 8. 1. Lac k of Efficac y ........................................................................ 8 1
8. 4. 9. Me dical De vice Deficie ncies ...................................................................... 8 2
8. 4. 9. 1. Ti me Peri o d f or Detecti n g Me dical De vice Deficie ncies ......... 8 2
8. 4. 9. 2. F oll o w -U p of Me dical De vice Deficie ncies.............................. 8 2
8. 4. 9. 3. Pr o m pt Re p orti n g of De vice Deficie ncies t o t he S p o ns or ........ 8 2
8. 4. 9. 4. Re g ulat or y  Re p orti n g Re q uire me nts f or De vice 
Deficie ncies ....................................................................................... 8 3
8. 4. 1 0. Vacci nati o n Err ors .................................................................................... 8 3
8. 5. P har mac o ki netics ....................................................................................................8 4
8. 6. Ge netics ................................................................................................................... 8 4
8. 6. 1. S pecifie d Ge netics ...................................................................................... 8 4
8. 7. Bi o mar kers .............................................................................................................. 8 4
8. 8. I m m u n o ge nicit y Assess me nts ................................................................................. 8 4
8. 9.
................................................................................................... 8 5
8. 1 0. St u d y  Pr oce d ures................................................................................................... 8 5
8. 1 0. 1. C o m m u nicati o n a n d Use of Tec h n ol o g y .................................................. 8 5
8. 1 0. 2. Visit 1 – Vacci nati o n ( Da y 1)................................................................... 8 6
8. 1 0. 3. Visit 2 – 1- Wee k F oll o w -U p Visit ( After Vacci nati o n) – 6 t o 8 
D a y s After Visit 1 ............................................................................................ 8 9
8. 1 0. 4. Visit 3 – 4- Wee k F oll o w -U p Visit ( After Vacci nati o n) – 2 8 t o 3 5 
D a y s After Visit 1............................................................................................ 9 0
8. 1 0. 5. Visit 4 – 6- M o nt h F oll o w -U p Visit ( After Vacci nati o n) – 1 7 5 t o 
1 8 9 Da y s After Visit 1 ..................................................................................... 9 1
8. 1 0. 6. I LI S ur veilla nce ( All Partici pa nts) ............................................................ 9 1
8. 1 0. 6. 1. I LI Visit ( Wit hi n 5 Da y s After I LI O nset) .............................. 9 3
8. 1 0. 7. U nsc he d ule d Visit f or a Gra de 3 or S us pecte d Gra de 4 Reacti o n 
( React o ge nicit y S u bset Partici pa nts O nly) ...................................................... 9 5
8. 1 0. 8. A d diti o nal Pr oce d ures f or M o nit ori n g of P ote ntial M y ocar ditis or 
Pericar ditis .......................................................................................................9 6
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................ ................................................9 6
9. 1. Statistical H y p ot heses ............................................................................................. 9 7
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 10
9.1.1. Efficacy.......................................................................................................97
9.1.1.1. Noninferiority of Efficacy.........................................................97
9.1.1.2. Superiority of Efficacy..............................................................97
9.1.2. Immunogenicity..........................................................................................98
9.1.3. Estimands....................................................................................................98
9.1.3.1. Primary Estimands/Coprimary Estimands ................................98
9.1.3.2. Secondary Estimands ................................................................99
9.1.4. Multiplicity Adjustment..............................................................................99
9.2. Analysis Sets .........................................................................................................100
9.3. Statistical Analyses ...............................................................................................101
9.3.1. General Considerations.............................................................................101
9.3.1.1. Analyses for Binary Data ........................................................101
9.3.1.2. Analyses for Continuous Data.................................................102
9.3.2. Primary Endpoint(s)/Estimand(s) Analysis ..............................................103
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis..........................................105
9.3.4. Tertiary/Exploratory Endpoint(s) Analysis ..............................................107
9.3.5. Other Safety Analyses ..............................................................................110
9.4. Interim Analyses ...................................................................................................110
9.5. Analysis Timing ....................................................................................................110
9.6. Sample Size Determination...................................................................................111
9.6.1. Relative Vaccine Efficacy ........................................................................111
9.6.2. Immunogenicity........................................................................................112
9.6.3. Safety........................................................................................................113
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS........................................................................................................114
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations.............114
10.1.1. Regulatory and Ethical Considerations ..................................................114
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.......................................................................114
10.1.2. Financial Disclosure ...............................................................................115
10.1.3. Informed Consent Process ......................................................................115
10.1.4. Data Protection .......................................................................................116
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 11
10.1.5. Committees Structure .............................................................................116
10.1.5.1. Data Monitoring Committee .................................................116
10.1.6. Dissemination of Clinical Study Data ....................................................117
10.1.7. Data Quality Assurance ..........................................................................118
10.1.8. Source Documents..................................................................................119
10.1.9. Study and Site Start and Closure ............................................................120
10.1.10. Publication Policy.................................................................................120
10.1.11. Sponsor’s Medically Qualified Individual............................................121
10.2. Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ...................................................................122
10.2.1. Definition of AE .....................................................................................122
10.2.2. Definition of an SAE ..............................................................................123
10.2.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period..........................................................................125
10.2.4. Reporting of SAEs..................................................................................128
10.3. Appendix 3: Contraceptive and Barrier Guidance ..............................................130
10.3.1. Male Participant Reproductive Inclusion Criteria..................................130
10.3.2. Female Participant Reproductive Inclusion Criteria...............................130
10.3.3. Woman of Childbearing Potential ..........................................................131
10.3.4. Contraception Methods...........................................................................132
10.4. Appendix 4: Genetics..........................................................................................134
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments .....135
10.6. Appendix 6: Kidney Safety Monitoring Guidelines ...........................................137
10.6.1. Laboratory Assessment of Change in Kidney Function and 
Detection of Kidney Injury............................................................................137
10.6.2. Age-Specific Kidney Function Calculation Recommendations.............137
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI 
Equations.........................................................................................137
10.6.3. Adverse Event Grading for Kidney Safety Laboratory 
Abnormalities.................................................................................................137
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................138
10.8. Appendix 8: AEs, ADEs, SAEs, SADEs, USADEs, and Device 
Deficiencies: Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting in Medical Device Studies ...........................................140
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 2
1 0. 8. 1. Defi niti o n of A E a n d A D E ..................................................................... 1 4 0
1 0. 8. 2. Defi niti o n of S A E, S A D E, a n d U S A D E ................................................ 1 4 0
1 0. 8. 3. Defi niti o n of De vice Deficie nc y .............................................................1 4 1
1 0. 8. 4. Rec or di n g/ Re p orti n g a n d F oll o w -U p of Me dical De vice 
Deficie ncies .................................................................................................... 1 4 1
1 0. 8. 5. Re p orti n g of S A Es .................................................................................. 1 4 3
1 0. 8. 6. Re p orti n g of S A D Es ............................................................................... 1 4 3
1 0. 9. A p pe n di x 9: Criteria f or All o wi n g I ncl usi o n of Partici pa nts Wit h C hr o nic 
Sta ble HI V, H C V, or H B V I nfecti o n ...................................................................... 1 4 4
1 0. 1 0. A p pe n di x 1 0: Pr ot oc ol A me n d me nt Hist or y ..................................................... 1 4 5
1 0. 1 1. A p pe n di x 1 1: A b bre viati o ns ............................................................................. 1 5 7
1 1. R E F E R E N C E S ................................................................................................................ 1 6 1
LI S T O F T A B L E S
Ta ble 1.
Defi niti o ns of L CI , C CI, a n d I LI..............................................................4 3
Ta ble 2.
L ocal Reacti o n Gra di n g Scale .................................................................. 7 3
Ta ble 3.
S y ste mic E ve nt Gra di n g Scale.................................................................. 7 3
Ta ble 4.
Scale f or Fe ver .......................................................................................... 7 4
Ta ble 5.
........ 1 1 1
Ta ble 6.
H AIs Use d t o E val uate t he I m m u ne Res p o nses A gai nst I nfl ue nza, 
b y  Seas o n................................................................................................ 1 1 2
Ta ble 7.
Pr o ba bilit y  of O bser vi n g at Least 1 A E b y Ass u me d Tr ue E ve nt 
Rates Wit h Differe nt Sa m ple Sizes ........................................................ 1 1 3
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 13
1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Title:
A Phase 3, Randomized, Observer-Blinded Study to Evaluate the Efficacy, Safety, 
Tolerability, and Immunogenicity of a Modified RNA Vaccine Against Influenza Compared 
to Licensed Inactivated Influenza Vaccine in Healthy Adults 18 Years of Age or Older
Brief Title:
A Study to Evaluate the Efficacy, Safety, Tolerability, and Immunogenicity of a Modified 
RNA Vaccine Against Influenza in Adults 18 Years of Age or Older
Regulatory Agency Identification Number(s):
US IND Number:
27600
EudraCT Number:
N/A
ClinicalTrials.gov ID:
NCT05540522
Pediatric Investigational Plan Number:
N/A
Protocol Number:
C4781004
Phase:
3
Rationale:
Influenza is a major cause of morbidity and mortality worldwide, occurring in annual 
seasonal epidemics and occasionally in global pandemics. Because of the ongoing variability 
in circulating influenza viruses, recommendations for the viruses to be targeted by each 
influenza season’s vaccines reflect the global influenza virus surveillance that continues 
throughout the year in both hemispheres. This means that the schedule for vaccine 
production, release, and administration is highly compressed.
Over the last several years, the use of mRNA as the basis for potential vaccine candidates has 
shown increasing promise. Various approaches to optimize the response to mRNA vaccines 
have been used. This includes modRNA in which some nucleosides are replaced by naturally 
occurring modified nucleosides, such as pseudouridine, which decreases innate immune 
activation and increases translation. Two LNP-encapsulated modRNA vaccines encoding the 
SARS-CoV-2 spike protein have been developed in response to the public health emergency 
presented by the COVID-19 pandemic: BNT162b2 (Pfizer/BioNTech) and mRNA-1273 
(Moderna), with both vaccines demonstrating high effectiveness with no significant safety 
concerns during Phase 3 development. Since its first marketing authorization in December 
2020, over 4 billion doses of BNT162b2 have been distributed worldwide. Postauthorization 
safety surveillance has confirmed the safety profile observed in clinical trials and has also 
identified adverse reactions of anaphylaxis (estimated at 11.1 per million doses administered) 
and an increased risk of myocarditis and pericarditis. Myocarditis was reported more often 
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 4
after t he sec o n d C O VI D - 1 9 vacci nati o n a n d t he ris k was hi g hest i n y o u n ger males. Des pite 
differe nces i n t he s o urce of t he data, desi g n of t he re p orte d st u dies, ge o gra p hic re gi o n, or 
met h o d of ascertai n me nt, t he p ost mar ket i n g safety s ur veilla nce a n d o bser vati o nal st u dies 
c o n ver ge t o a ver y rare fre q ue nc y of my o car ditis after C O VI D - 1 9 vacci nati o n, ie , less t ha n 1 
e xtra case per 1 0, 0 0 0 vacci nees ( < 0. 0 1 %). 
E x perie nce wit h m o d R N A- base d C O VI D -1 9 vacci nes s u p p orts t he use of t he m o d R N A 
platf or m f or p ote ntial ra pi d de vel o p me nt of vacci nes e nc o di n g t he seas o nall y  a da pte d H 1, 
H 3, a n d 2 B H As f or t he pre ve nti o n of i nfl ue nza. P ote ntial a d va nta ges of t his platf or m 
i ncl u de accelerate d ma n ufact uri n g, t here by all o wi n g a later decisi o n as to t he H A strai ns t o 
i ncl u de i n t he seas o nal vacci ne, a n d p ote ntiall y hi g her efficac y relati ve t o c urre ntly lice nse d 
i nfl ue nza vacci nes.
A P hase 1 / 2 st u d y ( C 4 7 8 1 0 0 1) t o descri be t he safet y, t olera bilit y, a n d i m m u n o ge nicit y of a 
m o d R N A vacci ne a gai nst i nfl ue nza i n healt h y  i n di vi d uals was i nitiate d i n Se pte m ber 2 0 2 1 i n 
partici pa nts 6 5 t hr o u g h 8 5 y ears of a ge. T his st u d y  is bei n g c o n d ucte d acr oss 2 s u bst u dies –
S u bst u d y  A a n d S u bst u d y B – t o st u d y differe nt m o d R N A vacci ne sc he d ules a gai nst 
i nfl ue nza. Base d o n 2 8- d a y  safety a n d i m m u n o ge nicit y data fr o m t his st u d y, 1 d ose of qI R V 
e nc o di n g 2 A strai ns a n d 2 B strai ns has bee n selecte d f or st u d y i n P hase 3 . Base d o n P hase 2 
safety a n d i m m u n o ge nicit y  data, t he d ose le vel of qIR V b y  a ge strat u m is
µ g f or
partici pa n ts 1 8 t hr o u g h 6 4 y ears of a ge a n d 
µ g f or partici pa nts ≥6 5 y ears of a ge. T he 
latest res ults ca n be f o u n d i n t he I B f or qI R V.
T his is a P hase 3, ra n d o mize d, o bser ver- bli n de d st u d y  t o e val uate t he efficac y, safety, 
t olera bilit y, a n d i m m u n o ge nicit y of a si n gle d ose of qIR V a gai nst i nfl ue nza c o m pare d t o 
lice nse d i nacti vate d i nfl ue nza vacci ne i n healt h y a d ults 1 8 years of a ge a n d ol der (stratifie d 
b y  a ge: 1 8 t hr o u g h 6 4 a n d ≥6 5 y ears of a ge).
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 5
O bjecti ves, E n d p oi nts, a n d Esti m a n ds:
Please see t he ta ble bel o w f or t he defi niti o ns of L C I, C CI, I LI, a n d se vere L CI.
Defi niti o ns of L CI, C CI, a n d I LI
Acr o n y m
Defi niti o n
Per -pr ot oc ol I LI
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of at least 1 of t he f oll o wi n g res pirat or y s y m pt o ms 
c o nc urre ntl y wit h at least 1 of t he f oll o wi n g s yste mic s y m pt o ms:
Res pirat or y s y m pt o ms ( o n g oi n g f or at least 1 2 h o urs, or m ulti ple e pis o des w it hi n a 2 4-h o ur peri o d):





S y ste mic s y m pt o ms:

 




I LI ( m o difie d C D C defi niti o n)
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of at least 1 of t he f oll o wi n g res pirat or y s y m pt o ms ( o n g oi n g 
f or at least 12 h o urs, or m ulti ple e pis o des w it hi n a 2 4-h o ur peri o d) c o nc urre ntl y wit h a n oral te m perat ure > 3 7. 2° C ( > 9 9. 0° F):

S ore t hr oat or

C o u g h 
I LI ( W H O defi niti o n)
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of a c o u g h ( o n g oi n g f or at least 1 2 h o u rs, or m ulti ple e pis o des 
wit hi n a 2 4 -h o ur peri o d) c o nc urre ntl y wit h a n oral te m perat ure ≥3 8. 0° C ( ≥1 0 0. 4° F)
L CI
I nfl ue nza i nfecti o n c o nfir me d t hr o u g h R T-P C R or c ult ure at t he ce ntral la b orat or y , u nless ot her wise s pecifie d
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 16
Definitions of LCI, CCI, and ILI
Acronym
Definition
CCI 
Influenza infection confirmed through culture at the central laboratorya, unless otherwise specified
Severe LCI
Influenza infection confirmed through RT-PCR or culture at the central laboratory with associated per-protocol ILI resulting 
in hospitalization
Abbreviations: CCI = culture-confirmed influenza; HAI = hemagglutination inhibition assay; ILI = influenza-like illness; LCI = laboratory-confirmed 
influenza; RT-PCR = reverse transcription–polymerase chain reaction.
a.
An HAI, conducted at a central laboratory, will be used for antigenic characterization of influenza viruses recovered in cultured samples to determine if 
they are matched strains to the vaccine.
The study objectives, endpoints, and estimands are detailed below.
Objectives
Estimands
Endpoints
Primary Efficacy: 
Primary Efficacy:
Primary Efficacy:
Participants ≥65 Years of Age
To demonstrate that the efficacy of qIRV is 
noninferior to that of QIV against LCI associated 
with per-protocol ILI, in participants ≥65 years of 
age
In participants ≥65 years of age complying with the 
key protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated per-protocol 
ILI caused by any strain
To demonstrate that the efficacy of qIRV is 
superior to that of QIV against LCI associated with 
per-protocol ILI, in participants ≥65 years of age
In participants ≥65 years of age complying with the 
key protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated per-protocol 
ILI caused by any strain
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 17
Objectives
Estimands
Endpoints
Participants 18 Through 64 Years of Age
To demonstrate that the efficacy of qIRV is 
noninferior to that of QIV against LCI associated 
with per-protocol ILI, in participants 18 through 
64 years of age
In participants 18 through 64 years of age 
complying with the key protocol criteria (evaluable 
participants) at least 14 days after study 
intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated per-protocol 
ILI caused by any strain
To demonstrate that the efficacy of qIRV is 
superior to that of QIV against LCI associated with 
per-protocol ILI, in participants 18 through 64 years 
of age
In participants ≥18 through 64 years of age
complying with the key protocol criteria (evaluable 
participants) at least 14 days after study 
intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated per-protocol 
ILI caused by any strain
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 18
Objectives
Estimands
Endpoints
Primary Safety:
Primary Safety:
Primary Safety:
To define the safety and tolerability profile of 
qIRV, in participants 18 through 64 years of age 
and ≥65 years of age
In participants 18 through 64 years of age and 
≥65 years of age separately, receiving study 
intervention, the percentage of participants 
reporting:
!
Local reactions for up to 7 days following 
vaccination 
!
Systemic events for up to 7 days following 
vaccination
In participants 18 through 64 years of age and 
≥65 years of age separately and combined, 
receiving study intervention, the percentage of 
participants reporting:
!
AEs through 4 weeks after vaccination
!
SAEs through 6 months after vaccination
!
Local reactions (pain at the injection site, 
redness, and swelling)
!
Systemic events (fever, fatigue, headache, 
chills, vomiting, diarrhea, new or worsened 
muscle pain, and new or worsened joint pain)
!
AEs
!
SAEs
Secondary Efficacy:
Secondary Efficacy:
Secondary Efficacy:
To evaluate the efficacy of qIRV compared to QIV 
against LCI or CCI associated with different 
definitions of ILI, in participants 18 through 
64 years of age and ≥65 years of age
In participants 18 through 64 years of age and 
≥65 years of age separately, complying with the key 
protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
!
First-episode LCI cases with associated 
per-protocol ILI caused by all matched strains
!
First-episode LCI cases with associated 
per-protocol ILI caused by each matched strain
!
First-episode LCI cases with associated 
per-protocol ILI caused by all unmatched 
strains
!
RVE, defined as the relative reduction of the 
proportion of participants reporting CCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
!
First-episode CCI cases with associated 
per-protocol ILI caused by any strain
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 9
O bjecti ves
Esti m a n ds
E n d p oi nts

R V E, defi ne d as t he relati ve re d ucti o n of t he 
pr o p orti o n of partici pa nts re p o rti n g L CI 
ass ociate d wit h I LI, as defi ne d b y a p pl yi n g a 
m o difie d C D C defi niti o n, i n t he qI R V gr o u p 
c o m pare d t o t he QI V gr o u p

First -e pis o de L CI ass ociate d wit h I LI, as 
defi ne d b y a p pl yi n g a m o difie d C D C defi niti o n, 
ca use d b y a n y strai n

R V E, defi ne d as t he relati ve re d ucti o n of t he 
pr o p orti o n of partici pa nts re p orti n g L CI cases 
ass ociate d wit h I LI, as defi ne d b y a p pl yi n g t he 
W H O defi niti o n, i n t he qI R V gr o u p c o m pare d 
t o t he QI V gr o u p

First -e pis o de L CI cases ass ociate d w it h I LI, as 
defi ne d b y a p pl yi n g t he W H O defi niti o n, 
ca use d b y a n y strai n

R V E, defi ne d as t he relati ve re d ucti o n of t he 
pr o p orti o n of partici pa nts re p orti n g cases of 
i nfl ue nza, as c o nfir me d b y ce ntral R T -P C R,
l ocal R T-P C R , or c ult ure, wit h ass ociate d 
per -pr ot oc ol I LI i n t he qI R V gr o u p c o m pare d 
t o t he QI V gr o u p

First -e pis o de cases of i nfl ue nza, as c o nfir me d 
b y ce ntral R T -P C R, l ocal R T-P C R , or c ult ure, 
wit h ass ociate d per -pr ot oc ol I LI
Sec o n d ar y I m m u n o ge nicit y:
Sec o n d ar y I m m u n o ge nicit y:
Sec o n d ar y I m m u n o ge nicit y:
T o e val uate t he n o ni nferi orit y of i m m u ne res p o nse 
elicite d b y qI R V c o mpare d t o QI V , i n partici pa nts 
1 8 t hr o u g h 6 4 years of a ge a n d ≥6 5 years of a ge
(usi n g H AIs 
)
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se parat el y, c o mpl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partici pa nts), 
c o m paris o ns will be ma de usi n g H AIs 
 f or t he i nfl ue nza strai ns t hat are 
prese nt i n t he st u d y i nter ve nti o ns:

G M R of H AI titers f or eac h strai n i n qI R V 
reci pients c o m pare d t o QI V reci pie nts 4 wee ks 
after vacci nati o n

T he differe nce i n perce nta ge of partici pa nts 
ac hie vi n g ser oc o n versi o n f or eac h strai n at 
4 we e ks after vacci nati o n i n qI R V reci pie nts 
c o m pare d t o QI V reci pie nts
H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y W H O 
f or 
 i nfl ue nza vacci nes 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 0
O bjecti ves
Esti m a n ds
E n d p oi nts
T o e val uate t he n o ni nferi orit y of i m m u ne res p o nse 
elicite d b y qI R V c o mpare d t o QI V , i n partici pa nts 
1 8 t hr o u g h 6 4 years of a ge a n d ≥6 5 years of a ge
(usi n g H AIs
)
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se paratel y, c o m pl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partici pa nts), 
c o m paris o ns will be ma de usi n g H AIs  
 
 f or t he i nfl ue nza strai ns t hat are 
prese nt i n t he st u d y i nter ve nti o ns:

G M R of H AI titers f or eac h strai n i n qI R V 
reci pie nts c o m pare d t o QI V reci pie nts 4 wee ks 
after vacci nati o n

T he differe nce i n perce nta ge of partici pa nts 
ac hie vi n g ser oc o n versi o n f or eac h strai n at 
4 we e ks after vacci nati o n i n qI R V reci pie nts 
c o m pare d t o QI V reci pie nts
H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y W H O 
f or 
 i nfl ue nza vacci nes
T o descri be t he i m m u ne res p o nse elicite d b y qI R V, 
i n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se paratel y, c o m pl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partici pa nts) ,
c o m paris o ns will be ma de usi n g H AIs  
 
:

H AI G M Ts at baseli ne a n d 4 wee ks after 
vacci nati o n

H AI G M F R at 4 wee ks after vacci nati o n

T he pr o p orti o n of partici pa nts ac hie vi n g H AI 
ser oc o n versi o n f or eac h strai n at 4 wee ks after 
vacci nati o n 

T he pr o p orti o n of partici pa nts wit h H AI titers 
≥1: 4 0 f or eac h strai n at baseli ne a n d 4 w ee ks 
after vacci nati o n

H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n 
he mis p here seas o nal strai ns ( 2 × A, 2 × B) 
rec o m me n de d b y W H O f or 
 i nfl ue nza 
vacci nes

H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n 
he mis p here seas o nal strai ns ( 2 × A, 2 × B) 
rec o m me n de d b y W H O f or 
 
 i nfl ue nza vacci nes 

H AI titers f or t he 2 0 2 3 s o ut her n he mis p here
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y 
W H O f or 
 i nfl ue nza vacci nes

H A I titers f or t he 2 0 2 3 s o ut her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y 
W H O f or 
 i nfl ue nza 
vacci nes
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 1
O bjecti ves
Esti m a n ds
E n d p oi nts
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y:
Terti ar y/ E x pl or at or y: 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 2
O bjecti ves
Esti m a n ds
E n d p oi nts
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 3
O bjecti ves
Esti m a n ds
E n d p oi nts
T here are n o pri mar y  i m m u n o ge nicity o bjecti ves i n t his st u d y .
F or t he p ur p oses of t he st u d y  esti ma n ds:

Ser oc o n versi o n is defi ne d as a n H AI titer < 1: 1 0 pri or t o vacci nati o n a n d ≥1: 4 0 at t he ti me p oi nt of i nte rest, or a n H AI titer ≥1: 1 0 
pri or t o vacci nati o n wit h a 4 -f ol d rise at t he ti me p oi nt of i nterest
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 4
O ver all Desi g n:
T his is a P hase 3 , ra n d o mize d, o bser ver- bli n de d st u d y t o e val uate t he efficac y, safet y, 
t olera bilit y, a n d i m m u n o ge nicit y of qI RV e nc o di n g H A of 4 seas o nall y rec o m me n de d strai ns
( 2 A strai ns a n d 2 B strai ns) i n healt h y i n di vi d uals ≥1 8 ye ars of a ge.
U p t o a p pr o xi matel y  3 6, 2 0 0 partici pa nts will i nitiall y be e nr olle d i n t his st u d y a n d stratifie d 
b y  a ge as f oll o ws:

U p t o a p pr o xi matel y  
partici pa nts ≥6 5 y ears of a ge will be e nr olle d a n d 
ra n d o mize d 
 t o recei ve 1 d ose of eit her qI R V or seas o nal QI V c o m parat or.

U p t o a p pr o xi matel y  
partici pa nts 1 8 t hr o u g h 6 4 y ears of a ge will be e nr olle d a n d 
ra n d o mize d  
 t o recei ve 1 d ose of eit her qI R V or seas o nal QI V c o m parat or. E nr oll me nt 
of partici pa nts 1 8 t hr o u g h 6 4 y ears of a ge is c o nti n ge nt o n o btai ni n g satisfact or y  P hase 
1/ 2 data i n partici pa nts of t his a ge, a n d will pr ocee d o nl y if re g ulat or y a ut h orit y 
e n d orse me nt is o btai ne d t o d o s o. E nr oll me nt i nt o eac h of t he 2 a ge strata ( 1 8 t hr o u g h
6 4 a n d ≥6 5 y ears of a ge) ma y t heref ore occ ur i n de pe n de ntl y. Base d o n P hase 2 safet y a n d 
i m m u n o ge nicity data, t he d ose le vel of qI R V b y a ge strat u m is 
µ g f or partici pa nts
1 8 t hr o u g h 6 4 ye ars of a ge a n d 
µ g f or partici pa nts ≥6 5 y ears of a ge.

I n eac h a ge stratu m:

A p pr o xi matel y   
 partici pa nts will be i ncl u de d in a react o ge nicit y s u bset. F or 
partici pa nts i n t he react o ge nicit y  s u bset, a react o ge nicit y e-diar y  will be c o m plete d b y 
eac h partici pa nt f or 7 da ys f oll o wi n g vacci nati o n.

A p pr o xi matel y   
partici pa nts will be i ncl u de d i n a n i m m u n o ge nicity s u bset. 
Bl o o d s a m ples of a p pr o xi matel y 1 5 m L  will be c ollecte d f or i m m u n o ge nicit y 
assess me nts pri or t o vacci nati o n a n d at 4 wee ks a n d 6 m o nt hs after vacci nati o n .
A p pr o xi matel y  
partici pa nts ≥1 8 y ears of a ge will be as ke d t o c o nse nt t o 
alter nati vel y pr o vi di n g 5 0 -m L , rat her t ha n 1 5-m L, bl o o d sa m ples at t he sa me ti me 
p oi nts, w hic h will be use d f or i m m u n o ge nicit y  assess me nts as well as assa y 
de vel o p me nt. A n a d diti o nal o pti o nal bl o o d sa m ple of 5 0 m L ma y  be c ollecte d fr o m 
partici pa nts w h o c o nse nt t o t he ti me p oi nts s pecifie d i n Secti o n 1. 3 f or assess me nt of 
; the n u m ber of partici pa nts as ke d t o pr o vi de t hese 
sa m ples will be deter mi ne d b y  Pfizer, c o nti n ge nt o n o perati o nal c o nsi derati o ns.

Partici pa nts ma y  be e nr olle d i n eit her or b ot h of t he s u bsets descri be d a b o ve.
Efficac y  will be assesse d i n t his st u d y t hr o u g h s ur veilla nce f or I LI. F oll o wi n g vacci nati o n, 
all partici pa nts will be pr o m pte d a p pr o xi matel y wee kly t o c o m plete a q uesti o n naire, usi n g a n 
e-diar y  or e q ui vale nt tec h n ol o g y, desi g ne d t o i de ntif y I LI. T his q uesti o n naire will als o be 
c o m plete d a n y ti me t he partici pa nt de vel o ps s y m pt o ms of I LI. If a partici pa nt de vel o ps I LI,
2 mi dt ur bi nate s wa bs will be c ollecte d ( 1 fr o m eac h n ostril), eit her b y  t he partici pa nt or b y  
site staff at a n I LI visit . T hese s wa bs will t he n u n der g o R T - P C R a n d c ult ure testi n g at a 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C C
I
C CI
C C
I
C CI
C CI
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 26
Number of Participants:
Up to approximately 53,200 participants may be enrolled in the study.
Note: "Enrolled" means a participant's agreement to participate in a clinical study following 
completion of the informed consent process and randomization.
Study Population:
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants ≥18 years of age (or the minimum age of consent in 
accordance with local regulations) at Visit 1 (Day 1).
!
Refer to Appendix 3 for reproductive criteria for male (Section 10.3.1) and female 
(Section 10.3.2) participants.
Disease Characteristics:
!
Not applicable.
Other Inclusion Criteria:
2. Participants who are willing and able to comply with all scheduled visits, investigational 
plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.
Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included. Specific criteria for participants with 
known stable infection with HIV, HCV, or HBV can be found in Section 10.9.
4. Capable of giving signed informed consent as described in the protocol, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 27
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. 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.
2. History of severe adverse reaction associated with any vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
3. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
Note: Individuals who have had a splenectomy or have functional asplenia will be 
considered ineligible.
4. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
5. Allergy to egg proteins (egg or egg products) or chicken proteins.
Prior/Concomitant Therapy:
6. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, 
including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are 
administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for 
cancer or an autoimmune disease, or planned receipt throughout the study. 
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted.
7. Receipt of blood/plasma products or immunoglobulin from 60 days before study 
intervention administration, or planned receipt throughout the study.
8. Vaccination with any investigational or licensed influenza vaccine within 6 months 
(175 days) before study intervention administration, or ongoing receipt of chronic 
antiviral therapy with activity against influenza.
9. Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 
vaccine within 14 days before or after study vaccination at Visit 1.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 8
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
1 0. Partici pat i o n i n ot her st u dies i n v ol vi n g a d mi nistrati o n of a st u d y i nter ve nti o n wit hi n 
2 8 da y s pri or t o, a n d/ or d uri n g, partici pati o n i n t his st u d y .
N ote: I n a d diti o n t o a d mi nistrati o n of i n vesti gati o nal pr o d ucts, st u d y  i nter ve nti o ns ma y 
i ncl u de a d diti o nal pr oce d ures, s uc h as c ollecti o n of bi ol o gical sa m ples. T heref ore, 
partici pa nts ma y  n ot be i n a n ot her st u d y w here b y pr oce d ures, s uc h as res pirat or y ill ness 
visits, ma y  i nterfere wit h c o m plia nce wit h t his st u d y’s pr ot oc ol.
Di a g n ostic Assess me nts:
N ot a p plica ble.
Ot her E xcl usi o n Criteri a :
1 1. I n vesti gat or site staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir fa mil y 
me m bers, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d s p o ns or a n d s p o ns or 
dele gate e m pl o y ees directl y i n v ol ve d i n t he c o n d uct of t he st ud y  a n d t heir fa mil y 
me m bers.
St u d y Ar ms a n d D ur ati o n :
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  eit her w he n t he y ha ve c o m plete d t he 
last visit ( Visit 4; 6- mo nt h foll o w - u p visit) or w he n t he i nfl ue nza seas o n e n ds (as j u d ge d b y 
Pfizer base d o n e pi de mi ol o gical data ), w hic he ver occ urs later.
St u d y I nter ve nti o ns
I nter ve nti o n N a me
qI R V
QI V
T y pe
Vacci ne
Vacci ne
T ar gete d infl ue nz a str ai ns
F or eac h seas o n - strai ns as 
rec o m me n de d b y W H O f or 
i nfl ue nza vacci nes.
F or eac h seas o n - strai ns as 
rec o m me n de d b y W H O f or 
i nfl ue nza vacci nes.
U nit d ose stre n gt h(s)
Base d o n P hase 2 safet y a n d 
i m m u n o ge nicit y data, t he d ose 
le vel of qI R V b y a ge strat u m is 
µ g f or partici pa nts 1 8 t hr o u g h 
6 4 years of a ge a n d  
µ g f or
partici pa nts ≥6 5 years of a ge.
As de taile d i n t he I P M.
R o ute of a d mi nistr ati o n
I ntra m usc ular i njecti o n
I ntra m usc ular i njecti o n
Use
E x peri me ntal
C o m parat or
I M P or NI M P
( gl o b al desi g n ati o n)
I M P
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or 
Pr o vi de d ce ntrall y b y t he s p o ns or
or l ocall y b y t he trial site (l ocal 
s o urci n g b y t he trial site is n ot 
per mitte d wit h o ut s p o ns or 
a p pr o val)
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 2 9
St u d y I nter ve nti o ns
I nter ve nti o n N a me
qI R V
QI V
P ac k a gi n g a n d la beli n g
St u d y i nter ve nti o n will be pr o vi de d 
i n a glass vial as o pe n-la bel s u p pl y.
Eac h vial will be la bele d per 
c o u ntr y re q uire me nt .
St u d y i nter ve nt i o n will be pr o vi de d 
as eit her a P F S or a glass vial as 
o pe n -la bel s u p pl y. Eac h 
dis pe nsa ble u nit will be la bele d per 
c o u ntr y re q uire me nt .
If t he pri mar y efficac y a nal ysis is n ot fa v ora ble, at t he s p o ns or’s discreti o n, t he st u d y  ma y be 
u n bli n de d earl y a n d, if still d uri n g t he i nfl ue nza seas o n, partici pa nts w h o were ra n d o mize d t o 
recei ve qI R V m a y be offere d a lice nse d QI V. T his QI V will be c o nsi dere d NI M P, s o urce d 
l ocall y b y site a n d a d mi nistere d per t he l ocal pac ka ge i nsert.
St atistic al Met h o ds
T he pla n ne d sa m ple size f or t he st u d y is base d o n statistical h y p ot hesis testi n g f or R V E of 
qI R V c o m pare d t o seas o nal QI V i n eac h a ge strat u m ( 1 8 t hr o u g h 6 4 a n d ≥6 5 y ears of a ge ).
T he st u d y  o bjecti ves for eac h a ge strat u m will be assesse d se paratel y wit h o ut m ulti plicit y  
a dj ust me nt. 
T here are 2 h y p ot heses ( n o ni nferi orit y a n d s u peri orit y ) f or t he st u d y pri mar y efficac y 
o bjecti ves i n eac h strat u m, w hic h will be teste d i n hierarc hical or der. T he h y p ot hesis of 
s u peri orit y of VE will be teste d o nl y  if t he n ull h y p ot heses f or n o ni nferi orit y of VE is 
rejecte d. T he h y p ot heses f or t he st u d y  sec o n dar y i m mu n o ge nicit y o bjecti ves f or eac h a ge 
strat u m will be teste d after t he pri mar y efficac y o bjecti ves i n t hat a ge strat u m ha ve bee n met.
T he st u d y  pri mar y n o ni nferi orit y efficac y o bjecti ve f or eac h a ge strat u m is ac hie ve d if t he 
l o wer b o u n d of t he 9 5 % CI f or R V E is m ore t ha n 
.
T he st u d y  pri mar y s u peri orit y efficac y o bjecti ve f or eac h a ge strat u m is ac hie ve d if t he l ower 
b o u n d of t he 9 5 % CI f or R V E is m ore t ha n 
.
N o ni nferi orit y of t he i m m u ne res p o nse elicite d b y qIR V c o m pare d t o a seas o nal QI V will be
e val uate d usi n g H AI titers a gai nst seas o nal strai ns rec o m me n de d by W H O f or t he 2 0 2 2- 2 0 2 3
n ort her n he mis p here i nfl ue nza seas o n. 
All R V Es will be esti mate d usi n g t he e xact c o n diti o nal bi n o mial met h o d. T he pri mar y  safety 
o bjecti ve will be e val uate d b y  descri pti ve s u m mar y statistics f or l ocal reacti o ns, s yste mic 
e ve nts, a n d A Es/ S A Es f or eac h vacci ne gr o u p. A 3- tier a p pr oac h will be use d t o s u m marize 
A Es.
T here is n o pla n ne d i nteri m a nal y sis f or t he st u d y.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C C
I

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 30
Ethical Considerations:
Potential risks to individual participants may include the following, mitigations for which are 
detailed in the protocol:
!
Local and systemic reactions to the vaccine may occur (injection site redness, injection 
site swelling, and injection site pain; fever, fatigue, headache, chills, muscle pain, and 
joint pain) following vaccination. These are common adverse reactions seen with other 
vaccines, as well as the COVID-19 vaccine BNT162b2, which is also based on modRNA. 
Local and systemic reactions to QIV may occur.
!
The safety profile of a novel vaccine is not yet fully characterized, so the full extent of 
risks is unknown.
!
Cases of anaphylaxis, myocarditis, and pericarditis have been reported after authorization 
in recipients of BNT162b2.
!
Participants will be required to attend healthcare facilities during the global SARS-CoV-2 
pandemic. Without appropriate social distancing and PPE, there is a potential for 
increased exposure to SARS-CoV-2.
!
Venipuncture will be performed during the study. There is the risk of bleeding, bruising, 
hematoma formation, and infection at the venipuncture site.
!
Midturbinate swabs will be collected by site staff at any in-person ILI visit. Midturbinate 
swabs will be self-collected by the participant at any ILI visit conducted as a telehealth 
visit. There is a risk of nasal bleeding or injury.
Benefits to individual participants may be:
!
Receipt of a potentially efficacious influenza vaccine at no cost to the participant, and 
provision of the immunogenicity results in a subset of participants.
!
Active surveillance for and access to evaluation of respiratory illnesses.
!
Contributing to research to help others.
Considering the measures taken to minimize risks to study participants, the potential risks 
identified in association with qIRV are justified by the anticipated benefits that may be 
afforded to participants.
1.2. Schema
Not applicable.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 34
2. INTRODUCTION
2.1. Study Rationale
This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, 
tolerability, and immunogenicity of a single dose of qIRV against influenza compared to 
licensed inactivated influenza vaccine in healthy adults 18 years of age and older.
2.2. Background
2.2.1. Influenza
Influenza is a major cause of morbidity and mortality worldwide, occurring in annual 
seasonal epidemics and occasionally in global pandemics.1 Symptomatic influenza infection 
causes a febrile illness with respiratory and systemic symptoms,2 although it may often be 
asymptomatic.3 The risk of complications and hospitalization from influenza is higher in 
people ≥65 years of age, young children, and people with certain underlying medical 
conditions. In the US, an average of >200,000 hospitalizations per year are related to 
influenza,4 while the annual global number of deaths is estimated to range from almost 
300,000 to over 600,000.5 The burden of disease is significant among 18- through 
64-year-olds; in the US, the estimated flu disease burden for the 2019-2020 season was 
380,209 hospitalizations, with 160,888 accounted for by those 18 through 64 years of age.6
The same data estimated that the US annual mortality burden among all ages was 
20,342 deaths, with 7911 occurring among 18- through 64-year-olds.6 Vaccination coverage
for influenza among adults ≥18 years of age was 48.4% during that season.7
Influenza viruses are part of the Orthomyxoviridae family and are divided into 3 genera or 
types (A, B, and C) based upon antigenic differences in the nucleoprotein and matrix protein. 
Influenza A viruses are further classified into subtypes based upon the membrane 
glycoproteins, HA and NA.8 The RNA genome is segmented, which allows genetic 
reassortment among viruses of the same type.8 This genetic instability can result in the 
phenomenon known as antigenic shift, involving a major change in 1 or both of the HAs and 
NAs, which, if efficiently transmissible, can result in a pandemic. More common are multiple 
point mutations in the genome, leading to more minor changes in the HA and NA, known as 
antigenic drift.4 This genetic instability is what necessitates vaccines that are tailored
annually.4
2.2.2. Influenza Vaccination
The first influenza vaccines were licensed in the 1940s,9 and now a number of different types 
of vaccine exist: inactivated, recombinant, and LAIV.10 The viruses that form the basis for 
inactivated vaccines are replicated in either embryonated hens’ eggs or mammalian cell 
lines,11 and some are combined with an adjuvant, such as MF59, to improve the immune 
response, particularly important in older individuals.10 Multivalent vaccines are produced for 
routine seasonal immunization, targeting 3 or 4 influenza viruses.10 Trivalent vaccines target 
2 A subtypes and 1 B virus, although these have been replaced by quadrivalent vaccines,
which target an additional B virus (to cover 2 antigenically distinct lineages).12 Standard 
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 3 5
i nacti vate d vacci nes ge nerall y c o ntai n 1 5 µ g of eac h H A f or a d ult i ntra m usc ular i njecti o n, 
alt h o u g h t he hi g h - d ose i nacti vate d vacci ne c o ntai ns 6 0 µ g of eac h H A.1 3
Beca use of t he o n g oi n g varia bilit y i n circ ulati n g i nfl ue nza vir uses, rec o m me n dati o ns f or t he 
vir uses t o be tar gete d b y eac h i nfl ue nza seas o n’s vacci nes reflect t he gl o bal i nfl ue nza vir us
s ur veilla nce t hat c o nti n ues t hr o u g h o ut t he ye ar i n b ot h he mis p heres. 1 3 T his mea ns t hat t he 
sc he d ule f or vacci ne pr o d ucti o n, release, a n d a d mi nistrati o n is hi g hl y c o m presse d.
2. 2. 2. 1. Assessi n g I nfl ue nz a V acci ne I m m u n o ge nicit y
De pe n de nt u p o n t he c o m p o ne nts i ncl u de d i n eac h i nfl ue nza vacci ne, vacci nati o n is i nte n de d 
t o i n d uce a nti b o dies a gai nst H A a n d/ or N A. 1 4 Strai n -s pecific i m m u n o ge nicit y ca n be 
meas ure d b y t he H AI a n d 
 assa ys, alt h o u g h a nti b o d y titers meas ure d b y 
t he H AI are m ost c o m m o nl y use d t o assess vacci ne res p o nses.1 3 I n ge neral, a n H AI titer 
bet wee n 1: 3 2 a n d 1: 4 0 is c o nsi dere d pr otecti ve at a gr o u p le vel. 1 3 T his is reflecte d i n 
re g ulat or y g ui da nce, w here, f or e xa m ple:
Ser oc o n versi o n is defi ne d as a pre vacci nati o n H AI titer < 1: 1 0 a n d a p ost vacci nati o n H AI 
titer ≥1: 4 0 or a pre vacci nati o n H AI titer ≥1: 1 0 a n d a mi ni m u m 4 -f ol d rise i n p ost vacci nati o n 
H AI a nt i b o d y titer.1 3
A reas o na ble statistical c orrelate f or a n efficac y  of 5 0 % t o 7 0 % a gai nst cli nical s ym pt o ms of 
i nfl ue nza is defi ne d as a n H AI titer of 1: 4 0.1 5
Re g ulat or y  g ui da nce all o ws f or a ut h orizati o n of a ne w seas o nal i nfl ue nza vacci ne o n t he 
basis of i m m u n o ge nicit y a n d/ or efficac y data.1 5 ,1 6
2. 2. 3. N ucle osi de -M o difie d m R N A V acci nes
O ver t he last se veral ye ars, t he use of m R N A as t he basis f or p ote ntial vacci ne ca n di dates has 
s h o w n i ncreasi n g pr o mise. 1 7 Vari o us a p pr oac hes t o o pti mize t he res p o nse t o m R N A vacci nes 
ha ve bee n use d. T his i ncl u des m o d R N A, i n w hic h s o me n ucle osi des are re place d b y 
nat urall y  occ urri n g m o difie d n ucle osi des, s uc h as pse u d o uri di ne, w hic h decrease i n nate 
i m m u ne acti vati o n a n d i ncrease tra nslati o n.1 7
T w o L N P -e nca ps ul ate d m o d R N A vacci nes e nc o di n g t he S A R S- C o V -2 s pi ke pr otei n ha ve 
bee n de vel o pe d i n res p o nse t o t he p u blic healt h e mer ge nc y  prese nte d by t he C O VI D - 1 9 
pa n de mic: B N T 1 6 2 b 2 ( Pfizer/ Bi o N Tec h) 1 8 a n d m R N A-1 2 7 3 ( M o der na). 1 9 M o d R N A vacci ne 
ca n di date d ose le vels u p t o 1 0 0 µ g 2 0 a n d 2 5 0 µ g 1 9 were st u die d i n t he 
ca n di date-selecti o n/ d ose-fi n di n g sta ge of de vel o p me nt f or t he 2 vacci nes, res pecti vely.
P hase 3 de vel o p me nt was c o n d ucte d wit h 2 d oses of B N T 1 6 2 b 2 3 0 µ g 1 8 a n d 2 d oses of 
m R N A - 1 2 7 3 1 0 0 µ g, 2 1 wit h b ot h vacci nes de m o nstrate d t o be hi g hl y  effecti ve wit h n o 
i de ntifie d si g nifica nt safet y c o ncer ns.1 8 ,2 1 Si nce its first mar keti n g a ut h orizati o n i n 
Dece m ber 2 0 2 0, o ver 4 billi o n d oses of B N T 1 6 2 b 2 ha ve bee n distri b ute d w orl d wi de . 
P osta ut h orizati o n safet y  s ur veilla nce has c o nfir me d t he safet y pr ofile o bser ve d i n cli nical 
trials a n d has als o i de ntifie d a d verse reacti o ns of a na p h yla xis (esti mate d at 1 1. 1 per milli o n 
d oses a d mi nistere d) a n d a n i ncrease d ris k of m y o car ditis a n d pericar ditis . M y ocar ditis was 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 3 6
re p orte d m ore ofte n after t he sec o n d C O VI D-1 9 vacci nati o n a n d t he ris k was hi g hest i n 
y o u n ger males. Des pite differe nces i n t he s o urce of t he data, desi g n of t he re p orte d st u dies, 
ge o gra p hic re gi o n, or met h o d of ascertai n m e nt, t he p ost mar ket i n g safet y s ur veilla nce a n d 
o bser vati o nal st u dies c o n ver ge t o a ver y  rare fre q ue nc y of my ocar ditis after C O VI D - 1 9 
vacci nati o n, ie, less t ha n 1 e xtra case per 1 0, 0 0 0 vacci nes ( < 0. 0 1 %). 2 2 ,2 3 ,2 4
2. 2. 4. P ote nti al f or m R N A I nfl ue nz a V acci nes
E x perie nce wit h m o d R N A -base d C O VI D -1 9 vacci nes s u p p orts t he use of t he m o d R N A 
platf or m f or p ote ntial ra pi d de vel o p me nt of vacci nes e nc o di n g t he seas o nall y  a da pte d H 1, 
H 3, a n d 2 B H As f or t he pre ve nti o n of i nfl ue nza.
T he m o d R N A platf or m w o ul d prese nt a n u m ber of p ote ntial a d va nta ges. Ma n ufact uri n g 
c o ul d be accelerate d as n o reass orta nt ste p is re q uire d t o pr o d uce ma n ufact uri n g strai ns. T his 
all o ws t he decisi o n o n H A se q ue nce t o be ma de later t ha n wit h c urre nt vacci nes, a n d n o e g g 
a da ptati o n is re q uire d, re d uci n g t he p r o ba bilit y of vacci ne bei n g mis matc he d wit h circ ulati n g 
strai ns. T he i n d ucti o n of n ot o nl y  a nti- H A a nti b o dies b ut als o p ote ntial C D 4 + a n d C D 8 + 
T- cell res p o nses (as see n wit h B N T 1 6 2 b 2)2 5 c o ul d i m pr o ve u p o n t he efficac y o bser ve d wit h 
e xisti n g i nfl ue nza vacci n es.
Si milar a d va nta ges w o ul d als o be hi g hl y rele va nt t o a pa n de mic i nfl ue nza vacci ne i n t he 
e ve nt t hat o ne is re q uire d.
2. 2. 5. Cli nic al O ver vie w
A P hase 1/ 2 st u d y  ( C 4 7 8 1 0 0 1) t o descri be t he safet y, t olera bilit y, a n d i m m u n o ge nicit y of a 
m o d R N A vacci ne a gai nst i nfl ue nza i n healt h y  i n di vi d uals was i nitiate d i n Se pte m ber 2 0 2 1 ,
i nitiall y i n partici pa nts 6 5 t hr o u g h 8 5 y ears of a ge. T his st u d y was c o n d ucte d acr oss 
2 s u bst u dies – S u bst u d y  A a n d S u bst u d y B. S u bst u d y  A descri bed t he safet y a n d 
i m m u n o ge nicity of mI R V A or B at 4 d ose le vels, bI R V e nc o di n g b ot h A a n d B strai n s i n
4 d ose -le vel c o m bi nati o ns, a n d qI R V e nc o di n g 2 A strai ns a n d 2 B strai ns at a d ose le vel of 
µ g per strai n. A d diti o nall y , S u bst u d y A descri bed:

T he i m m u ne res p o nse elicite d b y  lice nse d QI V f oll o wi n g pri or recei pt of a m o d R N A 
vacci ne, t o assess p ote ntial pri mi n g of t he i m m u ne res p o nse, a n d

T he i m m u ne res p o nse elicite d b y  mI R V A or B f oll o wi n g pri or recei pt of lice nse d QI V, 
t o assess if t he i m m u ne res p o nse f oll o wi n g QI V ma y  be e n ha nce d.
S u bst u d y  B descri bed t he safety a n d i m m u n o ge nicit y of t he f oll o wi n g vacci nati o n sc he d ules
i n partici pa nts 6 5 t hr o u g h 8 5 y ears of a ge :

2 D oses of qI R V e nc o di n g 2 A strai ns a n d 2 B strai ns at a d ose le vel of  
µ g per strai n,
a d mi nistere d 2 1 da ys a part.

2 D oses of lice nse d QI V , a d mi nistere d 2 1 da ys a part (as a c o ntr ol gr o u p).
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 3 7

A d ose of lice nse d QI V f oll o we d b y  a d ose of bIR V e nc o di n g 2 A strai ns at a d ose le vel 
of eit her  
or 
µ g per strai n, a d mi nistere d 2 1 da ys a part.

A d ose of lice nse d QI V a d mi nistere d c o nc urre ntl y i n t he o p p osite ar m wit h bI R V 
e nc o di n g 2 A strai ns at a d ose le vel of eit her 
or 
 µ g per strai n.

A d ose of bI R V e nc o di n g 2 A strai ns at a d ose le vel of 
µ g per strai n a d mi nistere d 
c o nc urre ntl y i n t he op p osite ar m wit h bI R V e nc o di n g 2 B strai ns at a d ose le vel of  
µ g 
per strai n .

A d ose of qI R V e nc o di n g 2 A strai ns a n d 2 B strai ns at t he f oll o wi n g dose le vel 
c o m bi nati o ns:

µ g per strai n

µ g per A strai n, a n d
µ g per B strai n

µ g per A strain , a n d 
 µ g per B strai n

A d ose of lice nse d QI V (as a c o ntr ol gr o u p).
A d diti o nall y , partici pa nts 1 8 t hr o u g h 6 4 y ears of a ge were i ncl u de d i n S u bst u d y  B o nl y  
d uri n g e x pa n de d e nr oll me nt: 2 4 0 partici pa nts 1 8 t hr o u g h 6 4 y ears of a ge were ra n d o mize d 
 t o recei ve eit her a si n gle
µ g d ose of q I R V (e nc o di n g 2 A strai ns a n d 2 B strai ns at a 
d ose le vel of 
µ g per strai n) or a si n gle
-µ g d ose of q I R V (e nc o di n g 2 A strai ns a n d 2 B 
strai ns at a d ose le vel of 
µ g per strai n).
At t he ti me of pr ot oc ol a me n d me nt 4 f or t his st u d y ( C 4 7 8 1 0 0 4), t he f i nal C S R is pe n di n g f or 
t he C 4 7 8 1 0 0 1 st u d y, b ut preli mi nar y  res ults ca n be f o u n d i n t he I B. Base d o n t hese safety 
a n d i m m u n o ge nicit y dat a fr o m St u d y  C 4 7 8 1 0 0 1, 1 d ose of qI R V e nc o di n g 2 A strai ns a n d 
2 B strai ns has bee n selecte d f or st u d y i n P hase 3 . Base d o n P hase 2 safet y a n d 
i m m u n o ge nicity data, t he d ose le vel of qI R V b y a ge strat u m is
 µ g f or partici pa nts
1 8 t hr o u g h 6 4 ye ars of a ge a n d 
 µ g f or partici pa nts ≥6 5 y ears of a ge.
2. 3. Be nefit/ Ris k Assess me nt
m o d R N A vacci nes e x pressi n g t he S A R S -C o V -2 s pi ke pr otei n ha ve bee n s h o w n t o be safe, 
a de q uatel y t olerate d, a n d efficaci o us i n t he pre ve nti o n of C O VI D -1 9 w he n a d mi nistere d as 
2 d oses at a 2 1 - t o 2 8-d a y  i nter val.1 8 ,2 1 T hese vacci nes ha ve bee n a ut h orize d i n ma n y  
c o u ntries ar o u n d t he w orl d, a n d si nce its first mar keti n g a ut h orizati o n i n Dece m ber 2 0 2 0, 
o ver 4 billi o n d oses of B N T 1 6 2 b 2 ha ve bee n distri b ute d w orl d wi de .
T his s u p p orts use of t he m o d R N A platf or m f or p ote ntiall y  ra pi d de vel o p me nt of vacci nes 
e nc o di n g t he seas o nall y a da pte d H 1, H 3, a n d 2 B H As f or t he pre ve nti o n of i nfl ue nza.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C C
I

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 38
To date, approximately 19,000 participants have been vaccinated with a qIRV modRNA 
influenza vaccine across a Phase 1/2 study (C4781001) and this Phase 3 study (C4781004). 
No safety concerns have been observed to date.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of qIRV may be found in the IB, which is the SRSD for this study. The SRSD 
for QIV is the Fluzone Quadrivalent USPI.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 39
2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Intervention(s): qIRV
Local and systemic reactions to the vaccine may 
occur (injection site redness, injection site swelling, 
and injection site pain; fever, fatigue, headache, 
chills, muscle pain, and joint pain) following 
vaccination.
These are common adverse reactions seen with 
other vaccines,26 as well as the COVID-19 vaccine 
BNT162b2, which is also based on modRNA. The 
most common events reported in a large-scale 
efficacy study with BNT162b2 (C4591001) were 
mild to moderate pain at the injection site, fatigue, 
and headache.18
1-Week follow-up reactogenicity data of 
194 participants who received mIRV, bIRV, or 
qIRV in C4781001 Substudy A and 
120 participants from C4781001 Substudy B 
showed most events to be mild to moderate in 
severity, with the most common events being pain 
at the injection site, fatigue, and headache.
The study employs the use of a reactogenicity 
e-diary, which allows the investigator to monitor 
local reactions and systemic events in real time 
through an electronic portal. Severe reactions will 
require an unscheduled telephone call, and visit if 
required, to be conducted per protocol.
All study participants will be observed for at least 
30 minutes after vaccination.
The safety profile of a novel vaccine is not yet fully 
characterized.
Although qIRVs are novel vaccines, they are based 
on the same platform (modRNA) as the COVID-19 
vaccine BNT162b2, which has been shown to have 
a positive benefit/risk profile.
AE and SAE reports will be collected from the 
signing of the ICD through 4 weeks and 6 months 
after the vaccination, respectively.
All participants will be observed for at least 
30 minutes after vaccination.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 40
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Cases of anaphylaxis, myocarditis, and pericarditis 
have been reported after authorization in recipients 
of BNT162b2.
Anaphylaxis: The estimated rate is 5.0 per million 
doses administered.27
Myocarditis and pericarditis have been reported 
following vaccination with mRNA COVID-19 
vaccines. Typically, the cases have occurred more 
often in younger men and after the second dose of 
the vaccine, within several days after vaccination.
These are generally mild cases, and individuals tend 
to recover within a short time following standard 
treatment and rest. Healthcare professionals should 
be alert to the signs and symptoms of myocarditis 
and pericarditis in vaccine recipients.
Specific reference to these risks is made within the 
ICD, with instruction to contact a healthcare 
professional if a case is suspected.
Receipt of any mRNA-platform SARS-CoV-2 
vaccine within 14 days before and 14 days after 
study vaccination is prohibited.
For anaphylaxis, there is an on-site 30-minute 
observation period after vaccination.
Instructions for handling suspected cases of 
myocarditis and pericarditis are found in 
Section 8.10.8.
Study Intervention: QIV
Local and systemic reactions to the vaccine may 
occur.
The following summary represents an example QIV 
safety profile: In adults 18 years of age and older, 
the most common (≥10%) injection-site reaction 
was pain (47%); the most common solicited 
systemic adverse reactions were myalgia (24%), 
headache (16%), and malaise (11%). In adults 
65 years of age and older, the most common 
(≥10%) injection site reaction was pain (33%); the 
most common solicited systemic adverse reactions 
were myalgia (18%), headache (13%), and malaise 
(11%).28
The study employs the use of a reactogenicity 
e-diary, which allows the investigator to monitor 
local reactions and systemic events in real time 
through an electronic portal. Severe reactions will 
require an unscheduled telephone call, and visit if 
required, to be conducted per protocol.
All study participants will be observed for at least 
30 minutes after vaccination.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 41
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Study Procedures
Participants will be required to attend healthcare 
facilities during the global SARS-CoV-2 pandemic.
Without appropriate social distancing and PPE, 
there is a potential for increased exposure to 
SARS-CoV-2.
Pfizer will work with sites to ensure appropriate 
COVID-19 prevention strategies.
Venipuncture will be performed during the study.
There is the risk of bleeding, bruising, hematoma 
formation, and infection at the venipuncture site.
Only appropriately qualified personnel will obtain 
the blood draw.
Midturbinate swabs will be collected by site staff at 
any in-person ILI visit. Midturbinate swabs will be 
self-collected by the participant at any ILI visit 
conducted as a telehealth visit.
There is a risk of nasal bleeding or injury.
Only appropriately qualified personnel will collect 
the midturbinate swabs at site visits.
Participants will be properly trained by site staff on 
self-collection of midturbinate swabs, in case the 
ILI visit is conducted as a telehealth visit.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 42
2.3.2. Benefit Assessment
Benefits to individual participants may be:
!
Receipt of a potentially efficacious influenza vaccine at no cost to the participant, and 
provision of the immunogenicity results in a subset of participants.
!
Active surveillance for and access to evaluation of respiratory illnesses.
!
Contributing to research to help others.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with qIRV are justified by the anticipated benefits that may be 
afforded to participants.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 4 3
3. O B J E C TI V E S, E N D P OI N T S, A N D E S TI M A N D S
Please see Ta ble 1 f or t he defi nit i o ns of LCI , C CI, I LI, a n d se vere LCI .
T a ble 1.
Defi niti o ns of L CI, C CI, a n d I LI
Acr o n y m
Defi niti o n
Per -pr ot oc ol I LI
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of at least 1 of t he f oll o wi n g res pirat or y s y m pt o ms 
c o nc urre ntl y wit h at least 1 of t he f oll o wi n g s yste mic s y m pt o ms:
Res pirat or y s y m pt o ms ( o n g oi n g f or at least 1 2 h o urs, or m ulti ple e pis o des w it hi n a 2 4-h o ur peri o d):





S y ste mic s y m pt o ms:





I LI ( m o difie d C D C defi niti o n)
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of at least 1 of t he f oll o wi n g res pirat or y s y m pt o ms ( o n g oi n g 
f or at least 1 2 h o urs, or m ulti ple e pis o des wit hi n a 2 4-h o ur peri o d) c o nc urre ntl y wit h a n oral te m perat ure > 3 7. 2° C ( > 9 9. 0° F):

S ore t hr oat or

C o u g h 
I LI ( W H O defi niti o n)
Occ urre nce ( ne w o nset or w orse ni n g of pree xisti n g c o n diti o n) of a c o u g h ( o n g oi n g f or at le ast 1 2 h o urs, or m ulti ple e pis o des 
wit hi n a 2 4 -h o ur peri o d) c o nc urre ntl y wit h a n oral te m perat ure ≥3 8. 0° C ( ≥1 0 0. 4° F)
L CI
I nfl ue nza i nfecti o n c o nfir me d t hr o u g h R T-P C R or c ult ure at t he ce ntral la b orat or y , u nless ot her wise s pecifie d
C CI 
I nfl ue nza i nfecti o n c o nfir me d t hr o u g h c ult ure at t he ce ntral la b orat or ya, u nless ot her wise s pecifie d
Se vere L CI
I nfl ue nza i nfecti o n c o nfir me d t hr o u g h R T -P C R or c ult ure at t he ce ntral la b orat or y wit h ass ociate d per -pr ot oc ol I LI res ulti n g 
i n h os pitalizati o n
a.
A n H AI, c o n d ucte d at a ce ntral la b orat or y, w ill be use d f or a nti genic c haracterizati o n of i nfl ue nza vir uses rec o vere d i n c ult ure d sa m ples t o deter mi ne if 
t he y are matc he d strai ns t o t he vacci ne.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 44
The study objectives, endpoints, and estimands are detailed below.
Objectives
Estimands
Endpoints
Primary Efficacy: 
Primary Efficacy:
Primary Efficacy:
Participants ≥65 Years of Age
To demonstrate that the efficacy of qIRV is 
noninferior to that of QIV against LCI associated 
with per-protocol ILI, in participants ≥65 years of 
age
In participants ≥65 years of age complying with the 
key protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated 
per-protocol ILI caused by any strain
To demonstrate that the efficacy of qIRV is superior 
to that of QIV against LCI associated with 
per-protocol ILI, in participants ≥65 years of age
In participants ≥65 years of age complying with the 
key protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated 
per-protocol ILI caused by any strain
Participants 18 Through 64 Years of Age
To demonstrate that the efficacy of qIRV is 
noninferior to that of QIV against LCI associated 
with per-protocol ILI, in participants 18 through 
64 years of age
In participants 18 through 64 years of age 
complying with the key protocol criteria (evaluable 
participants) at least 14 days after study 
intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated 
per-protocol ILI caused by any strain
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 45
Objectives
Estimands
Endpoints
To demonstrate that the efficacy of qIRV is superior 
to that of QIV against LCI associated with 
per-protocol ILI, in participants 18 through 64 years 
of age
In participants ≥18 through 64 years of age
complying with the key protocol criteria (evaluable 
participants) at least 14 days after study 
intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
First-episode LCI cases with associated 
per-protocol ILI caused by any strain
Primary Safety:
Primary Safety:
Primary Safety:
To define the safety and tolerability profile of 
qIRV, in participants 18 through 64 years of age 
and ≥65 years of age
In participants 18 through 64 years of age and 
≥65 years of age separately, receiving study 
intervention, the percentage of participants 
reporting:
!
Local reactions for up to 7 days following 
vaccination 
!
Systemic events for up to 7 days following 
vaccination
In participants 18 through 64 years of age and 
≥65 years of age separately and combined,
receiving study intervention, the percentage of 
participants reporting:
!
AEs through 4 weeks after vaccination
!
SAEs through 6 months after vaccination
!
Local reactions (pain at the injection site, 
redness, and swelling)
!
Systemic events (fever, fatigue, headache, 
chills, vomiting, diarrhea, new or worsened 
muscle pain, and new or worsened joint pain)
!
AEs
!
SAEs
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 46
Objectives
Estimands
Endpoints
Secondary Efficacy:
Secondary Efficacy:
Secondary Efficacy:
To evaluate the efficacy of qIRV compared to QIV 
against LCI or CCI associated with different 
definitions of ILI, in participants 18 through 
64 years of age and ≥65 years of age
In participants 18 through 64 years of age and 
≥65 years of age separately, complying with the key 
protocol criteria (evaluable participants) at least 
14 days after study intervention:
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
!
First-episode LCI cases with associated 
per-protocol ILI caused by all matched strains
!
First-episode LCI cases with associated 
per-protocol ILI caused by each matched strain
!
First-episode LCI cases with associated 
per-protocol ILI caused by all unmatched 
strains
!
RVE, defined as the relative reduction of the 
proportion of participants reporting CCI cases 
with associated per-protocol ILI in the qIRV 
group compared to the QIV group
!
First-episode CCI cases with associated per-
protocol ILI caused by any strain
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI 
associated with ILI, as defined by applying a 
modified CDC definition, in the qIRV group 
compared to the QIV group
!
First-episode LCI associated with ILI, as 
defined by applying a modified CDC 
definition, caused by any strain
!
RVE, defined as the relative reduction of the 
proportion of participants reporting LCI cases 
associated with ILI, as defined by applying the 
WHO definition, in the qIRV group compared 
to the QIV group
!
First-episode LCI cases associated with ILI, as 
defined by applying the WHO definition, 
caused by any strain
!
RVE, defined as the relative reduction of the 
proportion of participants reporting cases of 
influenza, as confirmed by central RT-PCR,
local RT-PCR, or culture, with associated per-
protocol ILI in the qIRV group compared to the 
QIV group
!
First-episode cases of influenza, as confirmed 
by central RT-PCR, local RT-PCR, or culture, 
with associated per-protocol ILI
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 4 7
O bjecti ves
Esti m a n ds
E n d p oi nts
Sec o n d ar y I m m u n o ge nicit y:
Sec o n d ar y I m m u n o ge nicit y:
Sec o n d ar y I m m u n o ge nicit y:
T o e val uate t he n o ni nferi orit y of i m m u ne res p o nse 
elicite d b y qI R V c o mpare d t o QI V , i n partici pa nts 
1 8 t hr o u g h 6 4 years of a ge a n d ≥6 5 years of a ge
(usi n g H AIs
)
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se paratel y, c o m pl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partici pa nts) ,
c o m paris o ns will be ma de usi n g H AIs 
 f or t he i nfl ue nza strai ns t hat are 
prese nt i n t he st u d y i nter ve nti o ns:

G M R of H AI titers f or eac h strai n i n qI R V 
reci pie nts c o m pare d t o QI V reci pie nts 4 wee ks 
after vacci nati o n

T he differe nce i n perce nta ge of partici pa nts 
ac hie vi n g ser oc o n versi o n f or eac h strai n at 
4 we e ks after vacci n ati o n i n qI R V reci pie nts 
c o m pare d t o QI V reci pie nts
H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y W H O 
f or 
 i nfl ue nza vacci nes 
T o e val uate t he n o ni nferi orit y of i m m u ne res p o nse 
elicite d b y qI R V c o mpare d t o QI V , i n partici pa nts 
1 8 t hr o u g h 6 4 years of a ge a n d ≥6 5 years of a ge
(usi n g H AIs
)
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se paratel y, c o m pl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partic i pa nts),
c o m paris o ns will be ma de usi n g H AIs  
 
 f or t he i nfl ue nza strai ns t hat are 
prese nt i n t he st u d y i nter ve nti o ns:

G M R of H AI titers f or eac h strai n i n qI R V 
reci pie nts c o m pare d t o QI V reci pie nts 4 wee ks 
after vacci nati o n

T he d iffere nce i n perce nta ge of partici pa nts 
ac hie vi n g ser oc o n versi o n f or eac h strai n at 
4 we e ks after vacci nati o n i n qI R V reci pie nts 
c o m pare d t o QI V reci pie nts
H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y W H O 
f or 
 i nfl ue nza vacci nes
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 4 8
O bjecti ves
Esti m a n ds
E n d p oi nts
T o descri be t he i m m u ne res p o nse elicite d b y qI R V, 
i n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge a n d 
≥6 5 years of a ge se paratel y, c o m pl yi n g wit h t he ke y 
pr ot oc ol criteria (e val ua ble partici pa nts) , 
c o m paris o ns will be ma de usi n g H AIs  
 
:

H AI G M Ts at baseli ne a n d 4 wee ks after 
vacci nati o n

H AI G M F R at 4 wee ks after vacci nati o n

T he pr o p orti o n of partici pa nts ac hie vi n g H AI 
ser oc o n versi o n f or eac h strai n at 4 wee ks after 
vacci nati o n 

T he pr o p orti o n of partici pa nts wit h H AI titers 
≥1: 4 0 f or eac h strai n at baseli ne a n d 4 w ee ks 
after vacci nati o n

H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n 
h e mis p here seas o nal strai ns ( 2 × A, 2 × B) 
rec o m me n de d b y W H O f or 
 
i nfl ue nza vacci nes

H AI titers f or t he 2 0 2 2 -2 0 2 3 n ort her n 
he mis p here seas o nal strai ns ( 2 × A, 2 × B) 
rec o m me n de d b y W H O f or 
 
 i nfl ue nza vacci nes 

H AI titers f or t he 2 0 2 3 s o ut her n he mis p here
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y 
W H O f or 
 i nfl ue nza vacci nes

H AI titers f or t he 2 0 2 3 s o ut her n he mis p here 
seas o nal strai ns ( 2 × A, 2 × B) rec o m me n de d b y 
W H O f or 
 i nfl ue nza 
vacci nes
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 4 9
O bjecti ves
Esti m a n ds
E n d p oi nts
Terti ar y/ E x pl or at or y : 
Terti ar y/ E x pl or at or y:
Terti ar y/ E x pl or at or y: 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 5 0
O bjecti ves
Esti m a n ds
E n d p oi nts
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 5 1
O bjecti ves
Esti m a n ds
E n d p oi nts
T here are n o pri mar y  i m m u n o ge nicity o bjecti ves i n t his st u d y .
F or t he p ur p oses of t he st u d y  esti ma n ds:

Ser oc o n versi o n is defi ne d as a n H AI titer < 1: 1 0 pri or t o vacci nati o n a n d ≥1: 4 0 at t he ti me p oi nt of i nterest, or a n H AI titer
≥1: 1 0 pri or t o vacci nati o n wit h a 4 -f ol d rise at t he ti me p oi nt of i nterest
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 5 2
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a P hase 3 , ra n d o mize d, o bser ver- bli n de d st u d y t o e val uate t he efficac y, safet y, 
t olera bilit y, a n d i m m u n o ge nicit y of qI RV e nc o di n g H A of 4 seas o nall y rec o m me n de d strai ns
( 2 A strai ns a n d 2 B strai ns) i n healt h y i n di vi d uals ≥1 8 ye ars of a ge.
U p t o a p pr o xi matel y  3 6, 2 0 0 partici pa nts will i nitiall y be e nr olle d i n t his st u d y a n d stratifie d 
b y  a ge as f oll o ws:

U p t o a p pr o xi matel y  
partici pa nt s ≥6 5 y ears of a ge will be e nr olle d a n d 
ra n d o mize d 
 t o recei ve 1 d ose of eit her qI R V or seas o nal QI V c o m parat or.

U p t o a p pr o xi matel y  
partici pa nts 1 8 t hr o u g h 6 4 ye ars of a ge will be e nr olle d a n d 
ra n d o mize d 
 t o recei ve 1 d ose of eit her qI R V or s eas o nal QI V c o m parat or. E nr oll me nt 
of partici pa nts 1 8 t hr o u g h 6 4 y ears of a ge is c o nti n ge nt o n o btai ni n g satisfact or y  P hase 
1/ 2 data i n partici pa nts of t his a ge, a n d will pr ocee d o nl y if re g ulat or y a ut h orit y 
e n d orse me nt is o btai ne d t o d o s o. E nr oll me nt i nt o eac h of t he 2 a ge strata ( 1 8 t hr o u g h
6 4 a n d ≥6 5 y ears of a ge) ma y t heref ore occ ur i n de pe n de ntl y. Base d o n P hase 2 safet y a n d 
i m m u n o ge nicity data, t he d ose le vel of qI R V b y a ge strat u m is 
 µ g f or partici pa nts
1 8 t hr o u g h 6 4 ye ars of a ge a n d 
µ g f or partici pa nts ≥6 5 y ears of a ge.

I n eac h a ge stratu m:

A p pr o xi matel y   
 partici pa nt s will be i ncl u de d i n a react o ge nicit y s u bset. F or 
partici pa nts i n t he react o ge nicit y  s u bset, a react o ge nicit y e-diar y  will be c o m plete d b y 
eac h partici pa nt f or 7 da ys f oll o w i n g vacci nati o n.

A p pr o xi matel y  
partici pa nts will be i ncl u de d i n a n i m m u n o ge nicit y s u bset. 
Bl o o d sa m ples of a p pr o xi matel y  1 5 m L  will be c ollecte d f or i m m u n o ge nicit y 
assess me nts pri or t o vacci nati o n a n d at 4 wee ks a n d 6 m o nt hs after vacci nati o n .
A p pr o xi matel y  
partici pa nts ≥1 8 y ears of a ge will be as ke d t o c o nse nt t o 
alter nati vel y pr o vi di n g 5 0 -m L , rat her t ha n 1 5-m L, bl o o d sa m ples at t he sa me ti me 
p oi nts, w hic h will be use d f or i m m u n o ge nicit y  assess me nts as well as assa y 
de vel o p me nt. A n a d diti o nal o pti o nal bl o o d sa m ple of 5 0 m L ma y  be c ollecte d fr o m 
partici pa nts w h o c o nse nt t o t he ti me p oi nts s pecifie d i n Secti o n 1. 3 f or assess me nt of 
; the n u m ber of partici pa nts as ke d t o pr o vi de t hese 
sa m ples will be deter mi ne d b y Pfizer, c o nti n ge nt o n o perati o nal c o nsi derati o ns.

Partici pa nts ma y  be e nr olle d i n eit her or b ot h of t he s u bsets descri be d a b o ve.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C C
I
C C
I
C CI
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 5 4
F oll o wi n g vacci nati o n, f or all partici pa nts, A Es will be c ollecte d fr o m i nf or me d c o nse nt 
si g ni n g t hr o u g h 4 wee ks f oll o wi n g vacci nati o n, a n d S A Es will be c ollecte d fr o m i nf or me d 
c o nse nt si g ni n g t hr o u g h 6 m o nt hs after vacci nati o n. I n a d diti o n, A Es occ urri n g u p t o 
4 8 h o urs after bl o o d dra ws or c ollecti o n of mi dt ur bi nate s wa bs will be c ollecte d. Deat hs, 
p ne u m o nia, a n d h os pitalizati o ns relate d t o I LIs will be rec or de d f or t he e ntire st u d y  d urati o n.
U p t o a p pr o xi matel y  5 3, 2 0 0 partici pa nts ma y be e nr olle d i n t he st u d y i n t otal.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
See Secti o n 2. 1 a n d Secti o n 2. 2. 4 .
4. 2. 1. Di versit y of St u d y P o p ul ati o n
See Secti o n 5 .
4. 2. 2. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
H u ma n re pr o d ucti ve safet y  data are n ot a vaila ble f or t he m o d R N A i nfl ue nza vacci nes use d i n 
t his st u d y, b ut t here is n o s us pici o n of h u ma n terat o ge nicit y base d o n t he i nte n de d 
p har mac ol o g y of t he c o m p o u n d. T he use of a hi g hl y  effecti ve met h o d of c o ntrace pti o n is 
re q uire d f or se x ual i nterc o urse i n v ol vi n g a W O C B P (see A p pe n di x 3 ).
4. 3. J ustific ati o n f or D ose
I n partici pa nts 6 5 t hr o u g h 8 5 years of a ge, si milar or hi g her a nti b o d y res p o nses a n d T-cell 
res p o nses were o bser ve d t o all 4 strai ns elicite d b y a si n gle d ose of qI R V (
µ g) c o m pare d 
t o qIR V ( 
µ g). A si n gle d ose of qI R V u p t o 
µ g was well t olerate d. B ase d o n t he t otalit y 
of data i n t his st u d y , a si n gle d ose of qI R V ( 
µ g) was selecte d as t he d ose t o be e val uate d 
i n partici pa nts ≥6 5 y ears of a ge i n t h is P hase 3 st u d y (C 4 7 8 1 0 0 4 ). 
I n partici pa nts 1 8 t hr o u g h 6 4 years of a ge, a nti b o d y a n d T-cell res p o nses were si milar o verall 
bet wee n qI R V  
 µ g) a n d qI R V ( 
µ g). A m o dest d ose -de pe n de nt i ncrease i n 
react o ge nicit y was o bser ve d bet wee n t he qI R V  
µ g) a n d qIR V (
 µ g) gr o u ps. Base d o n 
t he t otalit y of data i n t his st u d y, a si n gle d ose of qI R V  
µ g) was selecte d as t he d ose t o be 
e val uate d i n partici pa nts 1 8 t hr o u g h 6 4 ye ars of a ge i n t h is P hase 3 st u d y (C 4 7 8 1 0 0 4 ).
4. 4. E n d of St u d y Defi niti o n
T he e n d of t he st u d y is defi ne d as eit her t he date of t he last visit of t he last partici pa nt i n t he 
st u d y, or w he n t he fi nal pri mar y  efficac y a nalys is has bee n tri g gere d, w hic he ver occ urs later.
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  eit her w he n t he y ha ve c o m plete d t he 
last visit ( Visit 4) or w he n t he i nfl ue nza seas o n e n ds (as j u d ge d by Pfizer base d o n 
e pide mi ol o gical data) , w hic he ver occ urs later.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 55
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled, including 
participants across diverse and representative racial and ethnic backgrounds. If a 
prescreening tool is utilized for study recruitment purposes, it will include collection of 
information that reflects the enrollment of a diverse participant population including, where 
permitted under local regulations, age, sex, race, and ethnicity. 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.
Individual participants may not be enrolled in this study more than once.
Note: "Enrolled" means a participant's agreement to participate in a clinical study following 
completion of the informed consent process and randomization.
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 or female participants ≥18 years of age (or the minimum age of consent in 
accordance with local regulations) at Visit 1 (Day 1).
!
Refer to Appendix 3 for reproductive criteria for male (Section 10.3.1) and female 
(Section 10.3.2) participants.
Disease Characteristics:
Not applicable.
Other Inclusion Criteria:
2. Participants who are willing and able to comply with all scheduled visits, investigational
plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination 
(if required), and clinical judgment of the investigator to be eligible for inclusion in the 
study.
Note: Healthy participants with preexisting stable disease, defined as disease not 
requiring significant change in therapy or hospitalization for worsening disease during 
the 6 weeks before enrollment, can be included. Specific criteria for participants with 
known stable infection with HIV, HCV, or HBV can be found in Section 10.9.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 56
4. Capable of giving signed informed consent as described in the protocol, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. 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.
2. History of severe adverse reaction associated with any vaccine and/or severe allergic 
reaction (eg, anaphylaxis) to any component of the study intervention(s).
3. Immunocompromised individuals with known or suspected immunodeficiency, as 
determined by history and/or laboratory/physical examination.
Note: Individuals who have had a splenectomy or have functional asplenia will be 
considered ineligible.
4. Bleeding diathesis or condition associated with prolonged bleeding that would, in the 
opinion of the investigator, contraindicate intramuscular injection.
5. Allergy to egg proteins (egg or egg products) or chicken proteins.
Prior/Concomitant Therapy:
6. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, 
including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are 
administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for 
cancer or an autoimmune disease, or planned receipt throughout the study. 
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are 
permitted.
7. Receipt of blood/plasma products or immunoglobulin from 60 days before study 
intervention administration, or planned receipt throughout the study.
8. Vaccination with any investigational or licensed influenza vaccine within 6 months 
(175 days) before study intervention administration, or ongoing receipt of chronic 
antiviral therapy with activity against influenza.
9. Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 
vaccine within 14 days before or after study vaccination at Visit 1.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 57
Prior/Concurrent Clinical Study Experience:
10. Participation in other studies involving administration of a study intervention within 
28 days prior to, and/or during, participation in this study.
Note: In addition to administration of investigational products, study interventions may 
include additional procedures, such as collection of biological samples. Therefore, 
participants may not be in another study whereby procedures, such as respiratory illness 
visits, may interfere with compliance with this study’s protocol.
Diagnostic Assessments:
Not applicable.
Other Exclusion Criteria:
11. Investigator site staff directly involved in the conduct of the study and their family 
members, site staff otherwise supervised by the investigator, and sponsor and sponsor 
delegate employees directly involved in the conduct of the study and their family 
members.
5.3. Lifestyle Considerations
5.3.1. Contraception 
The investigator or their designee, in consultation with the participant, will confirm that the 
participant is utilizing an appropriate method of contraception for the individual participant 
and their partner(s) from the permitted list of contraception methods (see Appendix 3,
Section 10.3.4) and will confirm that the participant has been instructed in its consistent and 
correct use. At time points indicated in the SoA, the investigator or designee will inform the 
participant of the need to use acceptable effective contraception consistently and correctly 
and document the conversation and the participant’s affirmation in the participant’s chart.
Participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception, considering that their risk for pregnancy may have changed since 
the last visit.
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued and document the requirement to use an 
alternate protocol-specified method, including if the participant will no longer use abstinence 
as the selected contraception method, or if pregnancy is known or suspected in the participant 
or partner.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 58
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, and any SAEs.
Individuals who do not meet the criteria for participation in this study (screen failures) may 
be rescreened.
5.5. Criteria for Temporarily Delaying Enrollment/Randomization/Administration of 
Study Intervention
The following conditions may allow a participant to be randomized once the conditions have 
resolved and the participant is otherwise eligible. Participants meeting these criteria at Visit 1 
will be considered screen failures if enrollment has closed once the condition(s) has/have 
resolved.
1. Current febrile illness (oral temperature ≥100.4°F [≥38°C]) or other acute illness within 
48 hours before study intervention administration.
2. Receipt of any nonstudy vaccine within 14 days before study intervention administration
at Visit 1.
3. Anticipated receipt of any nonstudy vaccine within 14 days after study intervention 
administration at Visit 1.
4. Receipt of short-term (<14 days) systemic corticosteroids. Study intervention 
administration at Visit 1 should be delayed until systemic corticosteroid use has been 
discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or topical 
(skin or eyes) corticosteroids are permitted.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study interventions are all prespecified investigational, medical devices, and other 
interventions (eg, surgical and behavioral) intended to be administered to the study 
participants during the study conduct.
6.1. Study Intervention(s) Administered
Study interventions for this study will be:
Study Interventions
Intervention Name
qIRV
QIV
Type
Vaccine
Vaccine
Targeted influenza strains
For each season - strains as 
recommended by WHO for 
influenza vaccines.
For each season - strains as 
recommended by WHO for 
influenza vaccines.
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P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 5 9
St u d y I nt er ve nti o ns
I nter ve nti o n N a me
qI R V
QI V
U nit d ose stre n gt h(s)
Base d o n P hase 2 safet y a n d 
i m m u n o ge nicit y data, t he d ose 
le vel of qI R V b y a ge strat u m is 
µ g f or partici pa nts 1 8 t hr o u g h 
6 4 years of a ge a n d 
 µ g f or
partici pa nts ≥6 5 years of a ge.
As detaile d i n t he I P M
R o ute of a d mi nistr ati o n
I ntra m usc ular i njecti o n
I ntra m usc ular i njecti o n
Use
E x peri me ntal
C o m parat or
I M P or NI M P
( gl o b al desi g n ati o n)
I M P
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he s p o ns or 
Pr o vi de d ce ntrall y b y t he s p o ns or
or l ocall y b y t he trial site (l ocal 
s o urci n g b y t he trial site is n ot 
per mitte d wit h o ut s p o ns or 
a p pr o val)
P ac k a gi n g a n d l a beli n g
St u d y i nter ve nti o n will be pr o vi de d 
i n a glass vial as o pe n-la bel s u p pl y. 
Eac h vial will be la bele d per 
c o u ntr y re q uire me nt .
St u d y i nter ve nti o n will be pr o vi de d 
as eit her a P F S or a glass vial as 
o pe n -la bel s u p pl y. Eac h d is pe nsa ble 
u nit will be la bele d per c o u ntr y 
re q uire me nt.
If t he pri mar y efficac y a nal ysis is n ot fa v ora ble, at t he s p o ns or’s discreti o n, t he st u d y  ma y be 
u n bl i n de d early a n d, if still d uri n g t he i nfl ue nza seas o n, partici pa nts w h o were ra n d o mize d t o 
recei ve qI R V m a y be offere d a lice nse d QI V. T his QI V will be c o nsi dere d NI M P, s o urce d 
l ocall y b y site a n d a d mi nistere d per t he l ocal pac ka ge i nsert.
6. 1. 1. A d mi nistr ati o n
P artici pa nts will recei ve 1 d ose of eit her q I RV or QI V as ra n d o mize d at Visit 1 i n acc or da nce 
wit h t he st u d y’s S o A (Secti o n 1. 3 ). St u d y  i nter ve nti o n s h o ul d be a d mi nistere d 
i ntra m usc ularly i nt o t he delt oi d m uscle, prefera bl y of t he n o n d o mi na nt ar m. S t u d y 
i nter ve nti o n will be a d mi nistere d o nl y b y  a n u n bli n de d a d mi nis trat or.
Sta n dar d vacci nati o n practices m ust be o bser ve d a n d vacci ne m ust n ot be i njecte d i nt o bl o o d 
vessels. A p pr o priate me dicati o n a n d ot her s u p p orti ve meas ures f or ma na ge me nt of a n ac ute 
h y perse nsiti vit y  reacti o n s h o ul d be a vaila ble i n acc or da nce wit h l ocal g ui deli nes f or sta n dar d 
i m m u nizati o n practices.
A d mi nistrati o n of st u d y i nter ve nti o ns s h o ul d be perf or me d by a n a p pr o priatel y q ualifie d, 
trai ne d, a n d vacci ne-e x perie nce d me m ber of t he st u d y staff (e g, p hys icia n, n urse, p h ysicia n’s 
assista nt, n urse prac titi o ner, p har macist, or me dical assista nt) as all o we d b y l ocal, state, a n d 
i nstit uti o nal g ui da nce.
St u d y  i nter ve nti o n a d mi nistrati o n details will be rec or de d o n t he C R F.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

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6.1.2. Medical Devices
The comparator vaccines detailed in Section 6.1 may be provided as PFSs and, in which case, 
should be considered medical devices.
All medical device deficiencies (including malfunction, use error, and inadequate labeling) 
shall be documented and reported by the investigator throughout the clinical investigation 
(see Section 8.4.9) and appropriately managed by the sponsor.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm that appropriate conditions (eg, temperature) 
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, prepare, and/or administer study intervention.
3. 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 upon return to 
business.
4. Any excursions from the study intervention label storage conditions should be reported to 
Pfizer upon discovery along with actions taken. The site should actively pursue options 
for returning the study intervention to labeled storage conditions, 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 excursion definition and information to report for each excursion will be provided to 
the site in the IPM.
5. Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the label. See the IPM for allowable storage conditions of prepared study 
intervention.
6. Study interventions should be stored in their original containers.
7. The investigator, institution, head of the medical institution (where applicable), or 
authorized site staff 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.
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8. Further guidance and information for the final disposition of unused study interventions 
are provided in the IPM. 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 IPM.
6.2.1. Preparation and Dispensing
See the IPM for instructions on how to prepare the study intervention for administration.
Study intervention should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, nurse 
practitioner, pharmacy assistant/technician, or pharmacist) as allowed by local, state, and 
institutional guidance. A second staff member will verify the dispensing.
Study intervention will be prepared by qualified unblinded site personnel according to the 
IPM or package insert, and the study intervention will be administered in such a way as to 
ensure the participants remain blinded.
6.3. Assignment to Study Intervention
Allocation (randomization) of participants to vaccine groups will proceed through the use of 
an IRT system. The site personnel (study coordinator or specified designee) will be required 
to enter or select information including, but not limited to, the user’s ID and password, the 
protocol number, and the participant number. The site personnel will then be provided with a 
randomization number. The IRT system will provide a confirmation report containing the 
participant number, randomization number, and study intervention allocation assigned. This 
report will be provided to blinded or unblinded site staff as appropriate on the 
role/permission the user is granted and must be stored in the site’s blinded or unblinded files 
as appropriate.
Study intervention will be dispensed at the study visits summarized in the SoA.
The study-specific IRT reference manual and IPM will provide the contact information and 
further details on the use of the IRT system.
6.4. Blinding
This is an observer-blinded study.
6.4.1. Blinding of Participants
Participants will be blinded to their assigned study intervention.
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6.4.2. Blinding of Site Personnel
The study staff receiving, storing, dispensing, preparing, and administering the study 
interventions will be unblinded. All other study and site personnel, including the investigator
and investigator staff, will be blinded to assignment of study intervention. In particular, the 
individuals who evaluate participant safety will be blinded. Because there are differences in 
physical appearance of qIRV and QIV, these study interventions will be administered in a 
manner that prevents the study participants from identifying the study intervention group 
based on its appearance.
The PI will assign the responsibility of the unblinded dispensers/administrators to persons 
who will not participate in the evaluation of any study participant. To ensure adequate 
coverage, at least 2 unblinded dispensers/administrators will be assigned per site. Members 
of the study site staff or clinic pharmacy should fulfill these roles. Contact between the 
unblinded dispensers and study participants should be kept to a minimum. The investigator, 
study coordinator, and any site staff other than the unblinded dispensers/administrators must 
not be allowed to know the study intervention assigned to any study participant and must not 
be allowed to see the study intervention container contents.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study intervention records at the site(s) to verify that randomization/dispensing has been done 
accurately.
6.4.3. Blinding of the Sponsor
The majority of sponsor staff will be blinded to study intervention allocation during the 
study. All laboratory testing personnel performing serology assays will remain blinded to 
study intervention assigned/received throughout the study. The following sponsor/Pfizer 
staff, who will have no part in the blinded conduct of the study, will be unblinded (further 
details will be provided in a data blinding plan):
!
Those study team members who are involved in ensuring that protocol requirements for 
study intervention preparation, handling, allocation, and administration are fulfilled at the 
site will be unblinded for the duration of the study (eg, unblinded study manager, 
unblinded clinical research associate).
!
Unblinded clinician(s) who are not direct members of the study team and will not 
participate in any other study-related activities will review unblinded protocol deviations.
!
A team supporting interactions with, and analyses for, the DMC (see Section 10.1.5) will 
be unblinded.
!
An unblinded submissions team may be responsible for preparing unblinded analyses and 
documents to support regulatory activities that may be required while the study is 
ongoing. With the exception of the statisticians and programmers who will become 
unblinded at the participant level at the time of such a reporting event to perform the 
analyses, other members of this team will only be unblinded at the group level and not 
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have access to individual participant assignments. A separate group of statisticians and 
programmers will remain blinded and continue supporting the blinded conduct of the 
study after such an analysis.
The study will be unblinded to all sponsor/Pfizer staff when the study is completed.
6.4.4. Breaking the Blind
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s study 
intervention 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 study medical monitor
prior to unblinding a participant’s study intervention assignment unless this could delay 
further management of the participant. If a participant’s study intervention assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. The date 
and reason that the blind was broken must be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IPM will provide the contact information and 
further details on the use of the IRT system.
6.5. Study Intervention Compliance
Participants will be dosed at the site and they will receive study intervention directly from the 
unblinded administrator. The date and time of each dose administered in the clinic will be 
recorded in the source documents and CRF. The dose of study intervention and study 
participant ID will be confirmed at the time of dosing by a member of the study site staff 
other than the person administering the study intervention.
6.6. Dose Modification
Not applicable.
6.7. Continued Access to Study Intervention After the End of the Study
No study intervention will be provided to participants at the end of their study participation.
6.8. Treatment of Overdose
For this study, any dose of study intervention greater than 1 dose of study intervention within 
a 24-hour time period will be considered an overdose.
Pfizer does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the study medical monitor within 24 hours.
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2. Closely monitor the participant for any AEs/SAEs as medically appropriate and at least 
until the next scheduled follow-up.
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.
6.9. Prior and Concomitant Therapy
The following concomitant medications and vaccinations will be recorded in the CRF:
!
Prior receipt of any COVID-19 vaccine.
!
Prior receipt of any pneumococcal vaccine.
!
Licensed influenza vaccine, if received within the 12 months prior to enrollment.
!
Any vaccinations received from 28 days prior to study enrollment until the last visit 
(Visit 4).
!
Prohibited medications listed in Section 6.9.1, if taken, will be recorded and include start 
and stop dates, name of the medication, dose, unit, route, and frequency.
6.9.1. Prohibited During the Study
Receipt of the following vaccines and medications during the time periods listed below may 
exclude a participant from the per-protocol analysis from that point onward; however, it is 
anticipated that the participant would not be withdrawn from the study (see Section 7).
Medications should not be withheld if required for a participant’s medical care.
!
Unless considered medically necessary, no vaccines other than study intervention should 
be administered within 14 days before and 14 days after study vaccination at Visit 1.
!
Receipt of any mRNA-platform SARS-CoV-2 vaccine within 14 days before and 14 days 
after study vaccination at Visit 1.
!
Receipt of any other (nonstudy) seasonal influenza vaccine at any time during study 
participation is prohibited.
!
Receipt of chronic systemic treatment with known immunosuppressant medications, or 
radiotherapy, within 60 days before enrollment through conclusion of the study is 
prohibited.
!
Receipt of systemic corticosteroids (≥20 mg/day of prednisone or equivalent) for 
≥14 days is prohibited from 28 days prior to enrollment through 28 days after 
administration of the study intervention.
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!
Receipt of blood/plasma products or immunoglobulins within 60 days before enrollment 
through conclusion of the study is prohibited.
!
Prophylactic antipyretics and other pain medication to prevent symptoms associated with 
study intervention administration are not permitted. However, if a participant is taking a 
medication for another condition, even if it may have antipyretic or pain-relieving 
properties, it should not be withheld prior to study vaccination.
6.9.2. Permitted During the Study
!
Medication other than that described as prohibited in Section 6.9.1 required for treatment 
of preexisting conditions or acute illness is permitted.
!
Inhaled, topical, or localized injections of corticosteroids (eg, intra-articular or intrabursal 
administration) are permitted.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following: AEs, participant 
request, investigator request, and protocol deviation (including no longer meeting all the 
inclusion criteria, or meeting 1 or more exclusion criteria).
Note that discontinuation of study intervention does not represent withdrawal from the study.
If study intervention is permanently discontinued, the participant should remain in the study 
to be evaluated for safety and immunogenicity. See the SoA for data to be collected at the 
time of discontinuation of study intervention and follow-up for any further evaluations that 
need to be completed. Participants who remain in the study for safety evaluation will be 
contacted by telephone at 1 month and 6 months after their last study vaccination to record 
AEs and SAEs as described in Section 8.10.4 and Section 8.10.5, respectively.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, postvaccination study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study include the following:
!
Refused further study procedures;
!
Lost to follow-up;
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!
Death;
!
Study terminated by sponsor;
!
AEs;
!
Participant request; 
!
Investigator request;
!
Protocol deviation.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant. All attempts to contact the participant and information received during 
contact attempts must be documented in the participant’s source document. In any 
circumstance, every effort should be made to document participant outcome, if possible.
The investigator or his or her designee should capture the reason for withdrawal in the CRF 
for all participants.
If a participant withdraws from the study, they 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 will be performed and no 
additional data will be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
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 them 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 postvaccination 
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.
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7.3. Lost to Follow-Up
A participant will be considered lost to follow-up if the participant 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 attend a required study visit:
!
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. Counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether the participant wishes to and/or should continue in the 
study;
!
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record;
!
Should the participant continue to be unreachable, the participant will be considered to 
have withdrawn from the study.
8. STUDY ASSESSMENTS AND PROCEDURES
8.1. Administrative Procedures
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
The date of birth (as permitted by local regulations) will be collected to critically evaluate the 
immune response and safety profile by age.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that 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 
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P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 6 8
acti o ns t hat t he y ha ve ta ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
F or partici pa nts i n t he i m m u n o ge nicit y s u bset, t he mi ni mal bl o o d sa m pli n g v ol u me is 
a p pr o xi matel y 4 5 m L ( 1 5 m L  at Visits 1, 3, a n d 4). A p pr o xi matel y  
 partici pa nts will be 
as ke d t o c o nse nt t o alter nati vel y pr o vi di n g a p pr o xi matel y 1 5 0 m L ( 5 0 m L  at Visits 1, 3, a n d 
4) , w hic h will be use d f or i m m u n o ge nicity assess me nts a n d assa y de vel o p me nt. A d diti o nal 
o pti o nal w h ole bl o o d sa m ples of a p p r o xi matel y 5 0 m L at Visits 1, 2, 3, a n d 4 will be 
o btai ne d fr o m partici pa nts w h o c o nse nt f or 
 as detaile d i n Secti o n 4. 1 .
F or all partici pa nts, ot her a d diti o nal bl o o d sa m ples ma y  be ta ke n f or safet y assess me nts, 
pr o vi de d t he t otal v ol u me ta ke n d uri n g t he st u d y d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d 
of 6 0 c o nsec uti ve da ys.
8. 1. 1. Tele he alt h Visits
I n t he e ve nt t hat i n-cli nic st u d y visits ca n n ot be c o n d ucte d, e ver y  eff ort s h o ul d be ma de t o 
f oll o w u p o n t he safet y of st u d y partici pa nts at sc he d ule d visits per t he S o A or u nsc he d ule d 
visits. Tele healt h visits ma y be use d t o assess partici pa nt safet y a n d c ollect data p oi nts. 
Tele healt h i ncl u des t he e xc ha n ge of healt hcare i nf or mati o n a n d ser vices via 
telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, vi de oc o nfere nci n g s oft ware) re m otely, 
all o wi n g t he partici pa nt a n d t he i n vesti gat or t o c o m m u nicate o n as pect s of cli nical care, 
i ncl u di n g me dical a d vice, re mi n ders, e d ucati o n, a n d safety m o nit ori n g. T he f oll o wi n g 
assess me nts m ust be perf or me d d uri n g a tele healt h visit (see t he S o A ):

Pr oce d ures as i n dicate d f or Visit 4 (see Secti o n 8. 1 0. 5 ). F or partici pa nts n ot i ncl u de d 
i n t he i m m u n o ge nicit y s u bset o nl y.

Pr oce d ures as i n dicate d f or I LI visits ( Secti o n 8. 1 0. 6. 1 ).
St u d y  partici pa nts m ust be re mi n de d t o pr o m ptl y n otif y site staff a b o ut a ny c ha n ge i n t heir 
healt h stat us.
8. 1. 2. H o me He a lt h Visits
A h o me healt h care ser vice ma y be utilize d t o facilitate sc he d ule d visits. H o me healt h visits 
i ncl u de a healt hcare pr o vi der c o n d ucti n g a n i n-pers o n st u d y  visit at t he partici pa nt’s l ocati o n, 
rat her t ha n a n i n-pers o n st u d y  visit at t he site. T he f oll o wi n g ma y be perf or me d d uri n g a 
h o me healt h visit (see t he S o A ):

Pr oce d ures as i n dicate d f or Visits 2, 3, a n d 4 (see Secti o n 8. 1 0. 3 , Secti o n 8. 1 0. 4 , a n d 
Secti o n 8. 1 0. 5 , res pecti vel y)
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
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8.3. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled safety 
measurements may be obtained at any time during the study to assess any perceived safety 
issues.
A clinical assessment, including medical history, will be performed on all participants at their 
first visit to establish a baseline. Significant medical history and observations from any 
physical examination, if performed, will be documented in the CRF.
AEs and SAEs are collected, recorded, and reported as defined in Section 8.4.
Acute reactions within the first 30 minutes after administration of the study intervention will 
be assessed and documented in the AE CRF.
Safety parameters also include reactogenicity e-diary reports of local reactions and systemic 
events (including fever) and use of antipyretic medication that occur in the 7 days after 
administration of the study intervention from participants in the reactogenicity subset. These 
prospectively self-collected occurrences of local reactions and systemic events are graded as 
described in Section 8.3.4.
8.3.1. Physical Examinations
A physical examination may be performed at Visit 1 prior to vaccination, if clinically 
indicated. Physical examination findings collected during the study will be considered source 
data and will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 2) must be reported according to the processes in 
Sections 8.4.1 to 8.4.3.
8.3.2. Vital Signs
The participant’s oral temperature will be measured prior to vaccination. Additionally, 
weight and height will be measured prior to vaccination.
Any untoward vital sign findings that are identified during the active collection period and 
meet the definition of an AE or SAE (Appendix 2) must be reported according to the 
processes in Sections 8.4.1 to 8.4.3.
8.3.3. Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will not be collected in this study.
8.3.4. Reactogenicity Electronic Diary (Reactogenicity Subset Participants Only)
Participants in the reactogenicity subset will be required to complete a reactogenicity e-diary 
through an application installed on a provisioned device or on the participant’s own personal 
device. These participants will be asked to monitor and record local reactions, systemic 
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Table 3.
Systemic Event Grading Scale
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially 
Life-Threatening
(Grade 4)
Fatigue/tiredness
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe fatigue
Chills
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe chills
New or worsened 
muscle pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
muscle pain
New or worsened 
joint pain
Does not interfere 
with activity
Some interference 
with activity
Prevents daily routine 
activity
Emergency room visit 
or hospitalization for 
severe new or worsened 
joint pain
Abbreviation: IV = intravenous.
8.3.4.4. Fever
In order to record information on fever, a thermometer will be given to participants with 
instructions on how to measure oral temperature at home. Temperature will be collected in 
the reactogenicity e-diary in the evening daily during the reactogenicity e-diary reporting 
period. It will also be collected at any time during the reactogenicity e-diary data collection 
periods when fever is suspected. Fever is defined as an oral temperature ≥38.0°C (≥100.4°F).
The highest temperature for each day will be recorded in the reactogenicity e-diary.
Temperature will be measured and recorded to 1 decimal place. Temperatures recorded in 
degrees Fahrenheit will be programmatically converted to degrees Celsius and then 
categorized according to the scale shown in Table 4 during analysis.
If a fever of ≥39.0°C (≥102.1°F) is reported in the reactogenicity e-diary, a telephone contact 
should occur to ascertain further details and determine whether a site visit is clinically 
indicated. Only an investigator or medically qualified person is able to confirm a 
participant’s fever as >40.0°C (>104.0°F). If a participant experiences a confirmed fever 
>40.0°C (>104.0°F), the investigator must immediately notify the sponsor.
Table 4.
Scale for Fever
≥38.0-38.4°C (100.4-101.1°F)
>38.4-38.9°C (101.2-102.0°F)
>38.9-40.0°C (102.1-104.0°F)
>40.0°C (>104.0°F)
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8.3.4.5. Antipyretic Medication
The use of antipyretic medication to treat symptoms associated with study intervention 
administration will be recorded in the reactogenicity e-diary daily during the reporting period 
(Day 1 through Day 7).
8.3.5. 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 Visit 1, before the 
administration of the dose of study intervention. A negative pregnancy test result will be 
required prior to the participant’s receiving the study intervention. Pregnancy tests may also 
be repeated if requested by IRBs/ECs or if required by local regulations. In the case of a 
positive confirmed pregnancy, the participant will not be administered the study intervention
and will be withdrawn from the study.
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Section 10.2.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Section 10.8. Device deficiencies are covered in Section 8.4.9.
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 8.4.1, 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.
8.4.1. 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 
Visit 3. In addition, AEs occurring up to 48 hours after blood draws or collection of 
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midturbinate swabs must be recorded on the CRF. SAEs will be collected from the time the 
participant provides informed consent to Visit 4 (approximately 6 months after vaccination).
Deaths, pneumonia, and hospitalizations will be recorded as follows:
a.
If related to ILIs (as defined in Section 8.10.6) or their sequelae: these events will be 
recorded for the entire study duration on the relevant CRF page related to the ILI visit 
and will not be reported as SAEs/AEs (see Section 8.4.7).
b. If not related to ILIs or their sequelae: these events will be reported as AEs/SAEs as 
appropriate up to Visit 4.
Follow-up by the investigator continues throughout the active collection period and until the 
AE or SAE or its sequelae resolve or stabilize at a level acceptable to the investigator.
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant 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 
Vaccine SAE Reporting 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 they consider 
the event to be reasonably related to the study intervention, the investigator must promptly 
report the SAE to Pfizer using the Vaccine SAE Reporting Form.
8.4.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in
Section 8.4.1 are reported to Pfizer Safety on the Vaccine SAE Reporting Form immediately 
upon awareness and under no circumstance should this exceed 24 hours, as indicated in
Section 10.2. The investigator will submit any updated SAE data to the sponsor within 
24 hours of its being available.
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8.4.1.2. 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 8.4.1, 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.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.4.2. 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 Section 10.2.
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.
8.4.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.
Further information on follow-up procedures is provided in Section 10.2.
8.4.4. 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.
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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.
8.4.5. 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 EDP, EDB, and occupational exposure.
Any such exposures to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.4.5.1. 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 inseminates a 
female partner.
!
A female nonparticipant is found to be pregnant while being exposed or having been 
exposed to study intervention because of 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 inhalation or skin contact.
!
A male family member or healthcare provider who has been exposed to the study 
intervention by inhalation or skin contact then inseminates his female partner prior to 
or around the time of conception.
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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/participant’s partner, the investigator must report this 
information to Pfizer Safety on the Vaccine SAE Reporting 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 28 days after the study 
intervention.
!
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the Vaccine SAE Reporting 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 Vaccine SAE Reporting Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), 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 should be reported as an 
SAE;
!
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 
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the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.5.2. Exposure During Breastfeeding
An EDB occurs if:
!
A female participant is found to be breastfeeding while receiving or after discontinuing 
study intervention.
!
A female nonparticipant is found to be breastfeeding while being exposed or having been 
exposed to study intervention (ie, environmental exposure). An example of 
environmental EDB is a female family member or healthcare provider who reports that 
she is breastfeeding after having been exposed to the study intervention by inhalation or 
skin contact.
The investigator must report EDB 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 Vaccine SAE Reporting Form. When EDB 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 Vaccine SAE 
Reporting Form is maintained in the investigator site file.
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accordance with authorized use. 
However, if the infant experiences an SAE associated with such a drug, the SAE is reported 
together with the EDB.
8.4.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the Vaccine SAE Reporting 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 Vaccine SAE Reporting Form must be maintained in 
the investigator site file.
8.4.6. Cardiovascular and Death Events
Deaths will be recorded throughout the study as detailed in Section 8.4.1.
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
ILIs and their sequelae, including pneumonia and death, that are potentially consistent with 
any clinical efficacy endpoint definitions should not be recorded as AEs. These data will be 
captured as efficacy assessment data only on the relevant pages of the CRF, as these are 
expected endpoints.
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ILIs and their sequelae will not be reported according to the standard process for expedited 
reporting of SAEs, even though the event may meet the definition of an SAE. These events 
will be recorded on the ILI visit pages in the participant’s CRF within 1 day.
NOTE: However, if either of the following conditions applies, then the event must be 
recorded and reported as an SAE (instead of a disease-related event):
!
The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant.
OR
!
The investigator considers that there is a reasonable possibility that the event was related 
to study intervention.
ILIs and their sequelae will be reviewed by an internal blinded case reviewer. Any SAE that 
is determined by the internal case reviewer NOT to meet any clinical primary efficacy 
endpoint criteria is reported back to the investigator site of incidence. The investigator must 
report the SAE to Pfizer Safety within 24 hours of being made aware that the SAE did not 
meet endpoint criteria. The investigator’s SAE awareness date is the date on which the 
investigator site of incidence receives the SAE back from the internal case reviewers.
8.4.8. Adverse Events of Special Interest
The following events are considered AESIs:
!
A confirmed diagnosis of myocarditis or pericarditis. See Section 8.10.8 for additional 
procedures for monitoring of potential myocarditis or pericarditis.
AESIs are examined as part of routine safety data review procedures throughout the clinical 
trial and as part of signal detection processes. Should an aggregate analysis indicate that 
these prespecified events occur more frequently than expected, eg, based on epidemiological 
data, literature, or other data, then this will be submitted and reported in accordance with 
Pfizer’s safety reporting requirements. Aggregate analyses of safety data will be performed 
on a regular basis per internal SOPs.
All AESIs must be reported as an AE or SAE following the procedures described in 
Sections 8.4.1 through 8.4.4. An AESI is to be recorded as an AE or SAE on the CRF. In 
addition, an AESI that is also an SAE must be reported using the Vaccine SAE Reporting 
Form.
8.4.8.1. Lack of Efficacy
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to Pfizer 
Safety only if associated with an SAE.
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8.4.9. Medical Device Deficiencies
Medical devices being provided for use in this study are those listed in Section 6.1.2. In order 
to fulfill regulatory reporting obligations worldwide, the unblinded site staff is responsible 
for the detection and documentation of events meeting the definitions of device deficiency
that occur during the study with such devices.
The definition of a medical device deficiency can be found in Section 10.8.
Note: AEs and/or SAEs that are associated with a medical device deficiency will follow the 
same processes as other AEs or SAEs, as outlined in Sections 8.4.1 through 8.4.4 and 
Section 10.2 of the protocol.
8.4.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies that result in an incident will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
Importantly, reportable device deficiencies are not limited to problems with the device itself 
but also include incorrect or improper use of the device and even intentional misuse, etc.
If the unblinded site staff learns of any device deficiency at any time after a participant has 
been discharged from the study, and such deficiency is considered reasonably related to a 
medical device provided for the study, the unblinded site staff will promptly notify the 
sponsor.
The method of documenting medical device deficiencies is provided in Section 10.8.
8.4.9.2. Follow-Up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The unblinded site staff is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the unblinded site staff.
8.4.9.3. Prompt Reporting of Device Deficiencies to the Sponsor
When a device deficiency occurs: 
1. The unblinded site staff notifies the sponsor by a contact method as detailed in the IPM
within 1 business day of determining that the incident meets the protocol definition of a 
medical device deficiency.
2. The device deficiency must be recorded on the Medical Device Complaint form.
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3. If an AE (either serious or nonserious) associated with the device deficiency occurs, then 
the AE must be entered into the AE section of the CRF.
4. If an SAE associated with the device deficiency is brought to the attention of the 
unblinded site staff, the unblinded site staff must immediately notify Pfizer Safety of the 
SAE (see Section 8.4.1.1). All relevant details related to the role of the device in the 
event must be included in the Vaccine SAE Reporting Form as outlined in 
Sections 8.4.1.1 and 8.4.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.4.9.4. Regulatory Reporting Requirements for Device Deficiencies
The unblinded site staff will promptly report all device deficiencies occurring with any 
medical device provided for use in the study in order for the sponsor to fulfill the legal 
responsibility to notify appropriate regulatory authorities and other entities about certain 
safety information relating to medical devices being used in clinical studies.
The unblinded site staff, or responsible person according to local requirements (eg, the head 
of the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/EC.
8.4.10. Vaccination Errors
Vaccination 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.
Vaccinations errors are recorded and reported as follows:
Recorded on the 
Vaccination Error Page 
of the CRF
Recorded on the 
Adverse Event Page 
of the CRF
Reported on the Vaccine 
SAE Reporting Form to 
Pfizer Safety Within 
24 Hours of Awareness
All (regardless of whether 
associated with an AE)
Any AE or SAE associated 
with the Vaccination error
Only if associated with an 
SAE
Vaccination errors include:
!
Vaccination errors involving participant exposure to the study intervention;
!
Potential vaccination errors or uses outside of what is foreseen in the protocol that do or 
do not involve the study participant;
!
The administration of expired study intervention;
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 86
8.10.2. Visit 1 – Vaccination (Day 1)
Before enrollment and before any study-related procedures are performed, voluntary, written, 
study-specific informed consent will be obtained from the participant. Each signature on the 
ICD must be personally dated by the signatory. The investigator or his or her designee will 
also sign the ICD. A copy of the signed and dated ICD must be given to the participant. The 
source data must reflect that the informed consent was obtained before participation in the 
study.
It is anticipated that the procedures below will be conducted in a stepwise manner.
!
Assign a single participant number using the IRT system.
!
Obtain the participant’s demography (including date of birth, sex, race, and ethnicity).
The full date of birth will be collected (as permitted by local regulations) to critically 
evaluate the immune response and safety profile by age.
!
Obtain any medical history of clinical significance.
!
On the day of and prior to study intervention administration, perform a clinical 
assessment. If the clinical assessment indicates that a physical examination is necessary 
to comprehensively evaluate the participant, perform a physical examination and record 
any findings in the source documents and, if clinically significant, record findings on the 
medical history CRF.
!
Measure the participant’s height and weight.
!
On the day of and prior to study intervention administration, measure the participant’s 
oral temperature.
!
Record prior receipt of any COVID-19 vaccine as described in Section 6.9.
!
Record prior receipt of any pneumococcal vaccine as described in Section 6.9.
!
Record licensed influenza vaccine information, if received during the prior calendar year, 
as described in Section 6.9.
!
Record nonstudy vaccinations as described in Section 6.9.
!
On the day of and prior to study intervention administration, perform urine pregnancy test 
on WOCBP as described in Section 8.3.5.
!
If applicable, discuss contraceptive use as described in Section 4.2.2.
!
On the day of and prior to study intervention administration, ensure and document that all 
of the inclusion criteria and none of the exclusion criteria are met.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 8 7

O n t he da y  of a n d pri or t o st u d y i nter ve nti o n a d mi nistrati o n, ens ure t hat t he partici pa nt 
meets n o ne of t he te m p orar y  dela y criteria as descri be d i n Secti o n 5. 5 .

O n t he da y  of a n d pri or t o st u d y i nter ve nti o n a d mi nistrati o n , o btai n t he partici pa nt’s 
ra n d o mizati o n n u m ber a n d st u d y i nter ve nti o n all ocati o n usi n g t he I RT s ys te m.

O n t he da y  of a n d pri or t o st u d y i nter ve nti o n a d mi nistrati o n, for partici pa nts i n t he 
i m m u n o ge nicity s u bset, c ollect a bl o o d sa m ple (a p pr o xi matel y 1 5 m L ), bef ore 
a d mi nistrati o n of st u d y i nter ve nti o n, f or i m m u n o ge nicit y assess me nt. Alter nati vel y , if t he 
partici pa nt has c o nse nte d t o d o s o, c ollect a bl o o d sa m ple of a p pr o xi matel y 5 0 m L , rat her 
t ha n 1 5 m L , bef ore a d mi nistrati o n of st u d y  i nter ve nti o n, f or i m m u n o ge nicit y 
assess me nt /assa y de vel o p me nt.

If t he partici pa nt has c o nse nte d t o d o s o, c ollect a bl o o d sa m ple (a p pr o xi matel y  
5 0 m L ) f or 
.

U n bli n de d site staff me m ber(s) will dis pe nse/a d mi nister 1 d ose of st u d y  i nter ve nti o n i nt o 
t he delt oi d m uscle of t he (prefera bl y ) n o n d o mi na nt ar m. Please refer t o t he I P M f or 
f urt her i nstr ucti o n o n t his pr ocess.

Bli n de d site staff m ust o bser ve t he partici pa nt f or at least 3 0 mi n utes after st u d y  
i nter ve nti o n a d mi nistrati o n f or a ny ac ute reacti o ns. Rec or d a n y ac ute reacti o ns (i ncl u di n g 
ti me of o nset) i n t he partici pa nt’s s o urce d oc u me nts, o n t he A E C R F, a n d o n a n S A E 
f or m as a p plica ble.

Pr o vi de self -s wa b kits a n d i nstr ucti o ns o n self-c ollecti o n of mi dt ur bi nate s wa bs.

E x plai n t he e -diar y  tec h n ol ogies a vaila ble f or t his st u d y  (see Secti o n 8. 1 0. 1 ), a n d assist 
t he partici pa nt i n d o w nl oa di n g t he st u dy a p plicati o n o nt o t he partici pa nt’s o w n de vice or 
iss ue a pr o visi o ne d de vice if re q uire d.

F or partici pa nts i n t he react o ge nicity s u bset:

P r o vi de i nstr ucti o ns o n react o ge nicit y e-diar y  c o m pleti o n a n d as k t he partici pa nt t o 
c o m plete t he react o ge nicit y e-diar y  fr o m Da y 1 t hr o u g h Da y  7, wit h Da y 1 bei n g t he 
da y  of vacci nati o n.

Pr o vi de a meas uri n g de vice t o meas ure l ocal reacti o ns at t he i nject i o n site.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or i m me diatel y if t he 
partici pa nt e x perie nces a n y  of t he f oll o wi n g fr o m Da y 1 t hr o u g h Da y 7 after 
vacci nati o n ( w here Da y  1 is t he da y of vacci nati o n) t o deter mi ne if a n u nsc he d ule d 
react oge nicit y  visit is re q uire d:

Fe ver ≥3 9. 0 °C ( ≥1 0 2. 1° F).
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 8 8

Re d ness or s welli n g at t he i njecti o n site meas uri n g greater t ha n 1 0 c m 

Se vere pai n at t he i njecti o n site.

A n y  se vere sys te mic e ve nt.

P r o vi de i nstr ucti o ns o n I LI e-diar y  c o mpleti o n a n d as k t he partici pa nt t o c o m plete t he I LI 
e-diar y  if t he partici pa nt e x perie nces sy m pt o ms of I LI a n d w he n he/s he recei ves a 
re mi n der – t his will be at least wee kl y. See Secti o n 8. 1 0. 1 f or f urt her details.

Pr o vi de a t her m o meter f or rec or di n g dail y  te m perat ures (react o ge nicit y s u bset 
partici pa nts) a n d fe ver ( I LI s ur veilla nce); pr o vi de i nstr ucti o ns o n t heir use.

P r o vi de t he partici pa nt wit h a n I LI me m or y  ai d (Secti o n 8. 2. 1. 2 ) a n d instr uct t he 
partici pa nt t o use t he me m or y ai d bet wee n t he ti me of I LI sy m pt o m o nset a n d a n I LI visit 
t o rec or d t he se verity of I LI sy m pt o ms a n d t heir d urati o n.

Rec or d A Es as descri be d i n Secti o n 8. 4.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or if a me dicall y atte n de d e ve nt 
(e g, d oct or’s visit, e mer ge nc y  r o o m visit) or h os pitalizati o n occ urs.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or (t his c o ul d be via t he I LI 
e-diar y ) i m me diatel y if he or s he e x perie nces a ny I LI sy m pt o ms as detaile d i n 
Secti o n 8. 1 0. 6 .

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or if t he partici pa nt e x perie nces 
ac ute c hest pai n, s h ort ness of breat h, or pal pitati o ns (see Secti o n 8. 1 0. 8 ).

Sc he d ule a n a p p oi nt me nt f or t he partici pa nt t o ret ur n f or t he ne xt st u d y  visit.

R e mi n d t he partici pa nt t o bri n g t he e-diar y  t o t he ne xt visit.

C o m plete t he s o urce d oc u me nts.

T he i n vesti gat or or a n a ut h orize d desi g nee c o m pletes t he C R Fs a n d a n u n bli n de d 
dis pe nser/a d mi nistrat or u p dates t he st u d y  i nter ve nti o n acc o u nta bilit y rec or ds.
F or partici pa nts i n t he react o ge nicit y s u bset, t he i n vesti gat or or a p pr o priatel y  q ualifie d 
desi g nee re vie ws t he react o ge nicit y e-diar y  data o nli ne f oll o wi n g vacci nati o n t o e val uate 
partici pa nt c o m plia nce a n d as part of t he o n g oi n g safet y re vie w. Dail y re vie w is o pti mal 
d uri n g t he acti ve diar y  peri o d.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 8 9
8. 1 0. 3. Visit 2 – 1- Wee k F oll o w- U p Visit ( After V acci n ati o n) – 6 t o 8 D a ys After Visit 1
Visit 2 will o nl y  be c o n d ucte d f or partici pa nts w h o ha ve c o nse nte d t o pr o vi de t he o pti o nal 
bl o o d sa m ple f or 
. Visit 2 ma y  be c o m plete d as a 
h o me healt h visit (see Secti o n 8. 1. 2 ).

Rec or d A Es as descri be d i n Secti o n 8. 4 .

Rec or d n o nst u d y vacci nati o ns as descri be d i n Secti o n 6. 9 .

Rec or d pr o hi bite d me dicati o n use as descri be d i n Secti o n 6. 9. 1 .

If a p plica ble, disc uss c o ntrace pti ve use as descri be d i n Secti o n 4. 2. 2 .

C ollect a bl o o d sa m ple ( 5 0 m L ) f or 
.

F or partici pa nts i n t he react o ge nicit y s u bset:

Re vie w t he partici pa nt’s react o ge nicit y  e-diar y  data. If t he e-diar y  c ollecti o n peri o d is 
c o m plete, c ollect st o p dates of a n y react o ge nicit y e-diar y  e ve nts o n g oi n g o n t he last 
da y  t hat t he react o ge nicit y e-diar y  was c o m plete d a n d rec or d st o p dates i n t he C R F if 
re q uire d.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or i m me diatel y if he or s he 
e x perie nces a n y of t he f oll o wi n g fr o m D a y  1 t hr o u g h D a y  7 after vacci nati o n ( w here 
D a y  1 is t he da y of vacci nati o n) t o deter mi ne if a n u nsc he d ule d react o ge nicit y visit is 
re q uire d:

Fe ver ≥3 9. 0° C ( ≥1 0 2. 1° F).

Re d ness or s welli n g at t he i njecti o n site meas uri n g greater t ha n 1 0 c m 

Se vere pai n at t he i njecti o n site.

A n y  se vere sys te mic e ve nt.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or if a me dicall y atte n de d e ve nt 
(e g, d oct or’s visit, e mer ge nc y  r o o m visit) or h os pitalizati o n occ urs.

As k t he partici pa n t t o c o ntact t he site staff or i n vesti gat or if t he partici pa nt e x perie nces 
ac ute c hest pai n, s h ort ness of breat h, or pal pitati o ns (see Secti o n 8. 1 0. 8 ).

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or (t his c o ul d be via t he I LI 
e-diar y ) i m me diatel y if he or s he e x perie nces a ny I LI sy m pt o ms as detaile d i n 
Secti o n 8. 1 0. 6 .
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 9 0

Sc he d ule a n a p p oi nt me nt f or t he partici pa nt t o ret ur n f or t he ne xt st u d y  visit.

C o m plete t he s o urce d oc u me nts.

T he i n vesti gat or or a n a ut h orize d desi g nee c o m pletes t he C R Fs.
8. 1 0. 4. Visit 3 – 4- We e k F oll o w -U p Visit ( After V acci n ati o n) – 2 8 t o 35 D a ys After 
Visit 1
Visit 3 ma y  be c o m plete d as a h o me healt h visit (see Secti o n 8. 1. 2 ).

Rec or d A Es as descri be d i n Secti o n 8. 4 .

Rec or d n o nst u d y vacci nat i o ns as descri be d i n Secti o n 6. 9 .

Rec or d pr o hi bite d me dicati o n use as descri be d i n Secti o n 6. 9. 1 .

If a p plica ble, disc uss c o ntrace pti ve use as descri be d i n Secti o n 4. 2. 2 .

F or partici pa nts i n t he i m m u n o ge nicit y s u bset, c ollect a bl o o d sa m ple of a p pr o xi matel y  
1 5 m L  f or i m m u n o ge nicit y testi n g. Alter nati vely, if t he partici pa nt has c o nse nte d t o d o 
s o, c ollect a bl o o d sa m ple of a p pr o xi matel y 5 0 m L, rat her t ha n 1 5 m L , f or 
i m m u n o ge nicity assess me nt/assa y  de vel o p me nt.

If t he partici pa nt has c o nse nte d t o d o s o, c ollect a bl o o d sa m ple ( 5 0 m L) f or  
 

F or partici pa nts i n t he react o ge nicit y s u bset, r e vie w t he partici pa nt’s react o ge nicit y 
e-diar y  data. C ollect st o p dates of a ny react o ge nicit y  e-diar y  e ve nts o n g oi n g o n t he last 
da y  t hat t he react o ge nicit y e-diar y  was c o m plete d a n d rec or d st o p dates i n t he C R F if 
re q uire d.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or if a me dicall y atte n de d e ve nt 
(e g, d oct or’s visit, e mer ge nc y  r o o m visit) or h os pitalizati o n occ urs.

As k t he partici pa nt t o c o ntact t he site staff or i n vesti gat or (t his c o ul d be via t he I LI 
e-diar y ) i m me diatel y if he or s he e x perie nces a ny I LI sy m pt o ms as detaile d i n 
Secti o n 8. 1 0. 6 .

Rec or d a n y A Es t hat occ ur wit hi n t he 4 8 h o urs after t he bl o o d dra w as descri be d i n
Secti o n 8. 4 .

Sc he d ule a n a p p oi nt me nt f or t he partici pa nt t o ret ur n f or t he ne xt st u d y  visit.

C o m plete t he s o urce d oc u me nts.

T he i n vesti gat or or a n a ut h orize d desi g nee c o m pletes t he C R Fs.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 9 1
8. 1 0. 5. Visit 4 – 6- M o nt h F oll o w -U p Visit ( After V acci n ati o n) – 1 7 5 t o 1 8 9 D a ys After 
Visit 1
Visit 4 ma y  be c o n d ucte d as a h o me healt h visit f or all partici pa nts (see Secti o n 8. 1. 2 ). F or 
partici pa nts n ot i ncl u de d i n t he i m m u n o ge nicit y s u bset , Vi sit 4 ma y be c o n d ucte d as a 
tele healt h visit (see Secti o n 8. 1. 1 ).

Rec or d S A Es a n d p ne u m o nia as descri be d i n Secti o n 8. 4 .

Rec or d n o nst u d y  vacci nati o ns as descri be d i n Secti o n 6. 9 .

Rec or d pr o hi bite d me dicati o n use as descri be d i n Sect i o n 6. 9. 1 .

F or partici pa nts i n t he i m m u n o ge nicit y s u bset, c ollect a bl o o d sa m ple of a p pr o xi matel y  
1 5 m L  f or i m m u n o ge nicit y testi n g. Alter nati vel y, if t he partici pa nt has c o nse nte d t o d o 
s o, c ollect a bl o o d sa m ple of a p pr o xi matel y 5 0 m L , rat her t ha n 1 5 m L , f or 
i m m u n o ge nicity assess me nt /assa y de vel o p me nt.

If t he partici pa nt has c o nse nte d t o d o s o, c ollect a bl o o d sa m ple ( 5 0 m L) f or 
 

As k t he par tici pa nt t o c o ntact t he site staff or i n vesti gat or (t his c o ul d be via t he I LI 
e-diar y ) i m me diatel y if he or s he e x perie nces a ny I LI sy m pt o ms as detaile d i n 
Secti o n 8. 1 0. 6.

If directe d by Pfizer (e g, at t he e n d of t he i nfl ue nza seas o n ), collect t he partici pa nt’s 
e-diar y  or assist t he partici pa nt wit h re m o vi n g t he st u d y a p plicati o n fr o m his or her o w n 
pers o nal de vice ; if Visit 4 is bei n g c o n d ucte d as a tele healt h visit a n d t he partici pa nt has a 
pr o visi o ne d e -diar y  de vice, as k t he m t o ret ur n t his b y mail.

C o m plete t he s o urce d oc u me nts.

T he i n vesti gat or or a n a ut h orize d desi g nee c o m pletes t he C R Fs.

Rec or d a n y A Es t hat occ ur wit hi n t he 4 8 h o urs after t he bl o o d dra w as descri be d i n
Secti o n 8. 4 .
8. 1 0. 6. I LI S ur veill a nce ( All P artici p a nts)
If a partici pa nt e x perie nces a n occ urre nce ( ne w o nset or w orse ni n g of pr ee xisti n g c o n diti o n) 
of at least 1 of t he f oll o wi n g res pirat or y  sy m pt o ms c o nc urre ntl y  wit h at least 1 of t he 
f oll o wi n g sys te mic sy m pt o ms (irres pecti ve of percei ve d eti ol o g y  or cli nical si g nifica nce), he 
or s he is i nstr ucte d t o c o ntact t he site i m me diatel y a n d, if c o nfir me d, partici pate i n a n 
i n-pers o n or tele healt h visit as s o o n as p ossi ble, wit hi n 5 da y s after s ym pt o m o nset.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 9 2
Res pirat or y  sy m pt o ms ( o n g oi n g f or at least 1 2 h o urs, or m ulti ple e pis o des wit hi n a 2 4 -h o ur 
peri o d):





S y ste mic sy m pt o ms:





S ur veilla nce of p ote ntial I LI s ym pt o ms s h o ul d c o nti n ue e ve n if a partici pa nt has a p ositi ve 
R T -P C R or c ult ure test res ult earlier i n t he st u d y.
D uri n g t he 7 d a y s f oll o wi n g vacci nati o n, I LI s ym pt o ms t hat o verla p wit h s pecific s yste mic 
e ve nts (ie, fe ver, c hills, fati g ue/tire d ness, ne w or i ncreas e d m uscle pai n [m y al gia], or 
hea dac he ) s h o ul d n ot tri g ger an I LI visit u nless, i n t he i n vesti gat or’s o pi ni o n, t he cli nical 
pict ure is m ore i n dicati ve of I LI t ha n vacci ne react o ge nicit y.
Partici pa nts ma y  utilize an I LI e-diar y  t hr o u g h a n a p plicati o n (see Secti o n 8. 1 0. 1 ) i nstalle d 
o n a pr o visi o ne d de vice or o n t he partici pa nt’s pers o nal de vice t o pr o m pt hi m/ her wee kl y t o 
re p ort a ny s y m pt o ms a n d me dicall y atte n de d e ve nts (e g, tele p h o ne c o ns ultati o n wit h a 
me dical practiti o ner, d oct or’s visit, e mer ge nc y  r o o m visit, or h os pitalizati o n) t hat occ ur f or 
t he I LI. N ote t hat t his d oes n ot s u bstit ute f or a partici pa nt’s r o uti ne me di cal care. T heref ore, 
partici pa nts s h o ul d be e nc o ura ge d t o see k care, if a p pr o priate, fr o m t heir us ual pr o vi der.
T he s p o ns or ma y  i ncrease or decrease t he fre q ue nc y of t he wee kly c o ntacts or t he d urati o n of 
s ur veilla nce f or I LI base d o n i nfl ue nza s ur veilla nce data or ot her o perati o nal fact ors.
F oll o wi n g t he I LI visit bei n g i nitiate d, if ne w O R rec urre nt sy m pt o ms t hat meet per -pr ot oc ol 
re q uire me nts f or a n I LI visit e mer ge, t here is n o mi ni m u m ti me bet wee n s y m pt o m start 
a n d/ or res ol uti o n t hat w o ul d precl u de a n a d diti o nal I LI visit. I n vesti gat ors s h o ul d disc uss t he 
s ym pt o ms wit h t he partici pa nt a n d use t heir cli nical j u d g me nt t o deter mi ne if s uc h ne w O R 
rec urre nt sy m pt o ms are part of a si n gle I LI or a sec o n d I LI a n d , t heref ore, if a n a d diti o nal I LI 
visit is re q ui re d.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 9 3
8. 1 0. 6. 1. I LI Visit (Wit hi n 5 D a ys After I LI O nset)
T his visit ma y  be c o n d ucte d as a n i n-pers o n (e g, at t he st u d y site, or i n t he partici pa nt’s h o me
(h o me healt h visit , see Secti o n 8. 1. 2 ) or tele healt h visit (see Secti o n 8. 1. 1 ); a tele healt h visit 
in v ol ve s t he s hari n g of healt hcare i nf or mati o n a n d ser vices via a p pr o priate 
telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, vi de o -c o nfere nci n g s oft ware) re m otel y, 
t h us all o wi n g t he partici pa nt a n d i n vesti gat or t o c o m m u nicate o n as pects of cli nical care.
A s a partici pa nt’s I LI ma y  e v ol ve o ver ti me, se veral c o ntacts ma y be re q uire d t o o btai n t he 
f oll o wi n g i nf or mati o n:

If nee de d, pr o vi de self-s wa b kits a n d i nstr ucti o ns o n self-c ollecti o n of mi dt ur bi nate
s wa bs.

If t he visit is c o n d ucte d i n pers o n, o btai n 2 mi dt ur bi nate s wa bs (c ollecte d b y site staff), 
1 fr o m eac h n ostril. Alter nati vel y , if c o n d ucte d b y tele healt h, i nstr uct t he partici pa nt t o 
self-c ollect 2 mi dt ur bi nate s wa bs, 1 fr o m eac h n ostril, a n d s hi p t o t he ce ntral la b orat or y
f or assess me nt.

Perf or m cli nical assess me nt, i ncl u di n g te m perat ure a n d, if t he I LI visit is bei n g c o n d ucte d 
i n pers o n, res pirat or y rate. C ollect d etails of a n y I LI s ym pt o ms re p orte d b y t he 
partici pa nt (if use d, t he partici pa nt ma y refer t o t he I LI me m or y ai d t o recall details of 
t hese s ym pt o ms ) or n ote d via cli nical assess me nt, i ncl u di n g se verit y (see Secti o n 1 0. 2. 3 )
a n d d urati o n of

 
 
 
 
 
 
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 94
!
Following ILI symptom resolution, confirm, based on the participant’s own assessment:
!
Has the participant returned to the same level of health as prior to the onset of ILI?
!
Is the participant able to conduct daily activities as prior to the onset of ILI?
!
Has the participant required nonprofessional (eg, family member) assistance for ILI?
!
Collect ILI-related standard-of-care clinical and laboratory information. This includes, 
but is not limited to:
!
Number and type of any healthcare contact; duration of hospitalization and ICU stay; 
date of visit.
!
Mechanical ventilation use (if applicable).
!
Oxygen saturation.
!
Oxygen use (if applicable).
!
Local test results for influenza and any local noninfluenza respiratory pathogen 
testing, including the trade name of the testing platform used.
!
Results of x-rays or CT scans if performed.
!
Clinical diagnosis and sequelae, eg, pneumonia.
!
Concomitant medications used to treat ILI symptoms.
!
Death.
!
Record nonstudy vaccinations as described in Section 6.9.
!
Discuss contraceptive use as described in Section 4.2.2.
!
Record prohibited medication use as described in Section 6.9.1.
!
Record any AEs that occur within the 48 hours after the midturbinate swab as described 
in Section 8.4.
!
Record AEs as described in Section 8.4. Note: ILIs and their sequelae that are consistent 
with the clinical endpoint definition should not be recorded as AEs (see Section 8.4.7 for 
further details). These data will be captured as efficacy assessment data only on the 
relevant pages of the CRF, as these are expected endpoints.
!
Complete the source documents.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 95
!
The investigator or an authorized designee completes the CRFs.
8.10.7. Unscheduled Visit for a Grade 3 or Suspected Grade 4 Reaction (Reactogenicity 
Subset Participants Only)
If a Grade 3 local reaction (Section 8.3.4.2), systemic event (Section 8.3.4.3), or fever 
(Section 8.3.4.4) is reported in the reactogenicity e-diary, a telephone contact should occur to 
ascertain further details and determine whether a site visit is clinically indicated. If a 
suspected Grade 4 local reaction (Section 8.3.4.2), systemic event (Section 8.3.4.3), or fever 
(Section 8.3.4.4) is reported in the reactogenicity e-diary, a telephone contact or site visit 
should occur to confirm whether the event meets Grade 4 criteria.
A site visit must be scheduled as soon as possible to assess the participant unless any of the 
following is true:
!
The participant is unable to attend the unscheduled visit.
!
The local reaction/systemic event is no longer present at the time of the telephone 
contact.
!
The participant recorded an incorrect value in the reactogenicity e-diary (confirmation of 
a reactogenicity e-diary data entry error).
!
The PI or authorized designee determined it was not needed.
This telephone contact will be recorded in the participant’s source documentation and the 
CRF.
If the participant is unable to attend the unscheduled visit, or the PI or authorized designee 
determined it was not needed, any ongoing local reactions/systemic events must be assessed 
at the next study visit.
During the unscheduled visit, the reactions should be assessed by the investigator or a 
medically qualified member of the study staff, such as a study physician or a study nurse, as 
applicable to the investigator’s local practice, who will:
!
Measure oral temperature (°F/°C).
!
Measure minimum and maximum diameters of redness (if present).
!
Measure minimum and maximum diameters of swelling (if present).
!
Assess injection site pain (if present) in accordance with the grades provided in 
Section 8.3.4.2.
!
Assess systemic events (if present) in accordance with the grades provided in
Section 8.3.4.3.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 96
!
Assess for other findings associated with the reaction and record these on the AE page of 
the CRF if appropriate.
The investigator or an authorized designee will complete the unscheduled visit assessment 
page of the CRF.
8.10.8. Additional Procedures for Monitoring of Potential Myocarditis or Pericarditis
Any study participant who reports acute chest pain, shortness of breath, palpitations, or any 
other symptom(s) that might be indicative of myocarditis or pericarditis within 14 days after 
the study intervention administration should be specifically evaluated for possible 
myocarditis or pericarditis.
In addition to a clinical evaluation, the following should be performed:
!
ECG and
!
Measurement of the troponin level
If myocarditis or pericarditis is suspected based upon the initial evaluation, the following 
should also be performed:
!
Evaluation by a cardiologist,
!
Cardiac echocardiogram, and/or
!
Cardiac magnetic resonance study
Details of the symptoms reported, and results of the investigations performed, will be 
recorded in the CRF.
An evaluation is not required if, in the investigator’s opinion, the symptoms reported are 
more indicative of ILI. In that case, the procedures described in Section 8.10.6 should be 
performed.
9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is 
described here and further detailed in the 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.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 0
A fi xe d -se q ue nce testi n g pr oce d ure will be use d t o c o ntr ol t he o verall 1 -si de d t ype I err or at
f or all efficac y a n d i m m u n o ge nicit y h y p ot hes es wit hi n eac h a ge strat u m. T he 1 -si de d 
al p ha le vel of  
 will be use d f or eac h h y p ot hes is t hat ca n be tested base d o n t his strate g y .
All V E esti mati o ns wit h a n y a d diti o nal L C I cases c ollecte d after pri mar y a nal ysis will be 
descri pti vel y s u m marize d wit h a 9 5 % CI.
N o t y pe I err or will be all ocate d t o t he re mai ni n g sec o n dar y e n d p oi nts or e x pl orat or y 
e n d p oi nts.
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P o p ul ati o n
Descri pti o n
Scree n e d
All p artici pa nts w h o si g n t he IC D.
Ra n d o mize d
All partici pa nts w h o are assi g ne d a ra n d o mizati o n n u m ber i n 
t he I RT s yste m.
E val ua ble im m u n o ge nicit y
(H AIs 
 
)
All partici pa nts i ncl u de d i n t he i m m u n o ge nicit y  s u bset w h o 
are eli gi ble, recei ve t he st u d y i nter ve nti o n t o w hic h t he y  were 
ra n d o mize d, ha ve bl o o d dra w n f or assa y testi n g wit hi n t he 
s pecifie d ti me fra me after vacci nati o n, ha ve at least 1 vali d 
a n d deter mi na te assa y res ult (H AI s 
 
) at t he 4- wee k p ost vacci nati o n visit, a n d ha ve n o maj or 
pr ot oc ol vi olati o ns.
E val ua ble im m u n o ge nicit y
(H AIs 
 
)
All partici pa nts i ncl u de d i n t he i m m u n o ge nicit y  s u bset w h o 
are eli gi ble, recei ve t he st u d y i nter ve nti o n t o w hic h t he y were 
ra n d o mize d, ha ve bl o o d dra w n f or assa y testi n g wit hi n t he 
s pecifie d ti me fra me after vacci nati o n, ha ve at least 1 vali d 
a n d deter mi nate assa y res ult (H AI s 
 
) at t he 4-wee k p ost vacci nati o n visit, a n d ha ve n o maj or 
pr ot oc ol vi olati o ns.
mI T T i m m u n o ge nicit y
( H AIs 
 
)
All ra n d o mize d partici pa nts i n t he i m m u n o ge nicit y  s u bset 
w h o recei ve t he st u d y i nter ve nti o n a n d ha ve at least 1 vali d 
a n d deter mi nate assa y result (H AI s 
 
) after vacci nati o n.
mI T T i m m u n o ge nicit y
( H AIs 
 
)
All ra n d o mize d partici pa nts i n t he i m m u n o ge nicit y  s u bset 
w h o recei ve t he st u d y i nter ve nti o n a n d ha ve at least 1 vali d 
a n d deter mi nate assa y res ult (H AI s 
 
) after vacci nati o n.
E val ua ble efficac y  
All partici pa nts w h o are eli gi ble, recei ve t he st u d y 
i nter ve nti o n t o w hic h t he y were ra n d o mize d, a n d ha ve n o 
maj or pr ot oc ol vi olati o ns bef ore t he s y m pt o m o nset date of 
t he c o nfir me d L CI case, starti n g at least 1 4 da ys after 
vacci nati o n, a n d ass ociate d wit h a per -pr ot oc ol I LI .
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 1
P o p ul ati o n
Descri pti o n
mI T T efficac y
All ra n d o mize d partici pa nts w h o recei ve t he st u d y 
i nter ve nti o n.
Safet y
All partici pa nts w h o recei ve t he st u d y  i nter ve nti o n.
React o ge nicit y e -diar y  
safety
All partici pa nts w h o recei ve t he st u d y  i nter ve nti o n a n d ha ve
at least 1 da y of e-diar y  tra nsferre d f or react o ge nicit y.
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y  a nalys es are perf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data. 
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal y ses of t he pri mar y, sec o n dar y, a n d
tertiar y/e x pl orat or y e n d p oi nts.
9. 3. 1. Ge ner al C o nsi der ati o ns
CI s f or all e n d p oi nts i n t he statistical a nalys is will be prese nte d as 2-si de d at t he 9 5 % le vel 
u nless s pecifie d ot her wise.
F or all t he efficac y e n d p oi nts, t he a nal yses will be perf or me d o n b ot h t he e val ua ble efficac y 
p o p ulati o n a n d t he mI T T efficac y  p o p ulati o n; t he mai n a nal ys is will be base d o n t he 
e val ua b le efficac y p o p ulati o n . Partici pa nts will be s u m marize d acc or di n g t o t he vacci ne 
gr o u p t o w hic h t he y  were ra n d o mize d f or t he mI T T efficac y p o p ulati o n.
T he safet y a nal ys es are base d o n t he safet y p o p ulati o n. Partici pa nts will be s u m marize d b y  
vacci ne gr o u p acc or di n g t o t he st u d y  i nter ve nti o ns t he y act ually recei ve d. C o m pletel y 
missi n g react o ge nic it y e-diar y  data will n ot be i m p ute d; missi n g A E dates will be ha n dle d 
acc or di n g t o t he Pfizer safet y r ules.
F or all t he i m m u n o ge nicit y  e n d p oi nts (H AI s
), 
t he a nalys is will be base d o n t he e val ua ble i m m u n o ge nicit y p o p ulati o n s. A nti b o d y  titers 
bel o w t he L L O Q or de n ote d as B L Q will be set t o  
 f or i m m u n o ge nicit y a nal ys is.
All i m m u n o ge nicit y  a nal yses will be perf or me d after t he i m p utati o n of t he a nti b o d y 
c o nce ntrati o ns or a nti b o d y titers t hat are bel o w t he L L O Q .
A n a d diti o nal a nal ys is ma y be perf or me d base d o n t he mI T T i m m u n o ge nicit y  p o p ulati o n s
(H AIs
if t here is a lar ge e n o u g h differe nce i n 
sa m ple size bet wee n t he mI T T i m m u n o ge nicit y p o p ulati o n a n d t he e val ua ble 
i m m u n o ge nicity p o p ulati o n. Partici pa nts will be s u m marize d acc or di n g t o t he vacci ne gr o u p 
t o w hic h t he y were ra n d o mize d. Missi n g ser ol o g y  data will n ot be i m p ute d.
9. 3. 1. 1. A n al yses f or Bi n ar y D at a
Descri pti ve statistics f or bi nar y  varia bles (e g, pr o p orti o ns) are the perce nta ge ( %), t he 
n u merat or ( n) a n d t he de n o mi nat or ( N) use d i n t he perce nta ge calc ulati o n, a n d t he 9 5 % CIs 
w here a p plica ble.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 102
The exact 95% CI for binary endpoints for each group will be computed using the 
F distribution (Clopper-Pearson). The 95% CI for the between-group difference for binary 
endpoints will be calculated using the Miettinen and Nurminen method.
The 3-tier approach may be used to summarize AEs. For both Tier 1 (if any are identified 
during the study) and Tier 2 events, a 95% CI for the between-group difference in 
proportions will be calculated based on the Miettinen and Nurminen method. In addition, for 
Tier 1 events (if any), the asymptotic p-values will also be presented for the difference in 
proportions, based on the same test statistic and under the assumption that the test statistic is 
asymptotically normally distributed. For Tier 3 events, counts and percentages for each 
vaccine group will be provided.
9.3.1.2. Analyses for Continuous Data
Unless otherwise stated, descriptive statistics for continuous variables are n, mean, median, 
standard deviation, minimum, and maximum.
9.3.1.2.1. Geometric Means
The geometric means will be calculated as the mean of the assay results after making the 
logarithm transformation and then exponentiating the mean to express results on the original 
scale. Two-sided 95% CIs will be obtained by taking log transforms of assay results, 
calculating the 95% CI with reference to Student’s t distribution, and then exponentiating the 
confidence limits.
9.3.1.2.2. Geometric Mean Fold Rises
Fold rise is defined as the ratio of the results after vaccination to the results before 
vaccination. The calculations on fold rise are limited to participants with nonmissing values 
at both time points.
GMFRs will be calculated as the mean of the difference of logarithmically transformed assay 
results (later time point minus earlier time point) and exponentiating the mean. The 
associated 2-sided 95% CIs will be obtained by constructing CIs using Student’s 
t distribution for the mean difference on the logarithm scale and exponentiating the 
confidence limits.
9.3.1.2.3. Geometric Mean Ratios
The GMR will be calculated as the mean of the difference of logarithmically transformed 
assay results and exponentiating the mean. Two-sided CIs will be obtained by calculating CIs 
using Student’s t distribution for the mean difference of the logarithmically transformed 
assay results and exponentiating the confidence limits.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 3
9. 3. 1. 2. 4. Re verse C u m ul ati ve Distri b uti o n C ur ve s
E m pirical R C D Cs will pl ot pr o p orti o ns of partici pa nts wit h val ues e q ual t o or e xcee di n g a 
s pecifie d assa y val ue vers us t he i n dicate d assa y val ue, f or all o bser ve d assa y val ues. Data 
p oi nts will be j oi ne d b y  a ste p f u ncti o n wit h t he li ne first g oi n g d o w n a n d t he n ri g ht t o t he 
ne xt assa y  val ue.
9. 3. 2. Pri m ar y E n d p oi nt(s)/ Esti m a n d(s) A n al y sis
E n d p oi nt
St atistic al A n al ysis Met h o ds
Pri mar y  efficac y 
( partici pa nts 
≥6 5 ye ars of a ge)

R V E, defi ne d as t he relati ve ris k re d ucti o n of t he pro p orti o n of 
partici pa nts re p orti n g first-e pis o de LCI  cases wit h ass ociate d 
per -pr ot oc ol I LI ca use d b y a n y strai n, wit h s ym pt o m o nset at least 
1 4 da y s after vacci nati o n, i n t he qI R V gr o u p c o m pare d t o t he QI V
gr o u p, will be esti mate d al o n g wit h t he 2- si de d 9 5 % CI f or t he a ge 
strat u m wit h partici pa nts ≥6 5 ye ars of a ge.

T he a nal ys is of efficac y will use a c o n diti o nal e xact test base d o n
t he bi n o mial distri b uti o n of t he n u m ber of first-e pis o de L C I cases i n 
t he qI R V gr o u p, gi ve n t he t otal n u m ber of first-e pis o de cases i n b ot h
gr o u ps.

If t he l o wer c o nfi de nce li mit of 9 5 % f or R V E wit h partici pa nts 
≥6 5 ye ars of a ge at t he fi nal a nal ys is e xcee ds 
, t he n ull 
h y p ot hesis f or t he R V E n o ni nferi orit y  o bjecti ve will be rejecte d.

If t he l o wer c o nfi de nce li mit of 9 5 % f or R V E wit h partici pa nts 
≥6 5 ye ars of a ge at t he fi nal a nal ys is e xcee ds 
, t he n ull 
h y p ot hesis f or t he R V E s u peri orit y o bjecti ve will be rejecte d.

T he e val ua ble efficac y p o p ulati o n will be t he pri mar y p o p ulati o n f or 
efficac y a nal ys es. T he a nal ysis will be re peate d o n t he mI T T 
efficac y p o p ulati o n .

Se nsiti vit y a nal ysis o n t he pri mar y e n d p oi nt usi n g differe nt
met h o d(s) t o esti mate R V E , s uc h as by t he C o x pr o p orti o nal hazar ds 
m o del , ma y  be e x pl ore d i n t he S A P.
Pri mar y  efficac y 
( partici pa nts 
1 8 t hr o u g h 
6 4 ye ars of a ge)

R V E, defi ne d as t he relati ve ris k re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first-e pis o de L CI cases wit h ass ociate d 
per -pr ot oc ol I LI ca use d b y a n y strai n , wit h s ym pt o m o nset at least
1 4 da y s after vacci nati o n, i n t he qI R V gr o u p c o m pare d t o t he QI V
gr o u p, will be esti mate d al o n g wit h t he 2- si de d 9 5% CI  f or t he a ge 
strat u m wit h partici pa nts 1 8 t hr o u g h 6 4 ye ars of a ge.

T he a nal ys es f or efficac y wit h partici pa nts 1 8 t hr o u g h 6 4 ye ars of 
a ge will use t he e xact c o n diti o nal bi n o mial met h o d as descri be d 
a b o ve f or partici pa nts ≥6 5 y ears of a ge .
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C C
I

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 4
E n d p oi nt
St atistic al A n al ysis Met h o ds

If t he l o wer c o nfi de nce li mit of 9 5 % f or R V E wit h partici pa nts 
1 8 t hr o u g h 6 4 ye ars of a ge at t he fi nal a nal ys is e xcee ds 
, t he 
n ull h y p ot hesis f or t he R V E n o ni nferi orit y o bjecti ve will be rejecte d.

If t he l o wer c o nfi de nce li mit of 9 5 % f or R V E wit h parti ci pa nts 
1 8 t hr o u g h 6 4 ye ars of a ge at t he fi nal a nal ys is e xcee ds 
, t he n ull 
h y p ot hesis f or t he R V E s u peri orit y  o bjecti ve will be rejecte d.

T he e val ua ble efficac y p o p ulati o n will be t he pri mar y p o p ulati o n f or 
efficac y a nal ys es. T he a nal ysis will be re peat e d o n t he mI T T 
efficac y p o p ulati o n .

Se nsiti vit y a nal ysis o n t he pri mar y e n d p oi nt usi n g differe nt
met h o d(s) t o esti mate R V E , s uc h as by t he C o x pr o p orti o nal hazar ds 
m o del , ma y  be e x pl ore d i n t he S A P.
Pri mar y  safet y
( partici pa nts
1 8 t hr o u g h 
6 4 ye ars of a ge 
a n d ≥6 5 y ears of 
a ge)

P oi nt esti mates a n d t he ass ociate d e xact 2 -si de d 9 5 % CIs will be 
calc ulate d usi n g t he Cl o p per -Pears o n met h o d f or t he pr o p orti o n of 
partici pa nts re p orti n g eac h e ve nt (l ocal reacti o ns, s yste mic e ve nts, 
A Es, a n d S A Es) f or eac h vacci ne gr o u p b y  a ge strat u m (partici pa nts 
1 8 t hr o u g h 6 4 a n d ≥6 5 years of a ge ).

P oi nt esti mates a n d t he ass ociate d e xact 2 -si de d 9 5 % CI s will be 
calc ulate d usi n g t he Cl o p per -Pears o n met h o d f or t he pr o p orti o n of 
partici pa nts re p orti n g A Es a n d S A Es f or t he o verall p o p ulati o n 
(partici pa nts ≥1 8 ye ars of a ge) .

A Es a n d S A Es will be cate g orize d acc or di n g t o Me d D R A ter ms. A 
3- tier a p pr oac h will be use d t o s u m marize A Es. U n der t his 
a p pr oac h, A Es are classifie d i nt o 1 of 3 tiers: ( 1) Tier 1 e ve nts are 
pres pecifie d e ve nts of cli nical i m p orta nce a n d are i de ntifie d i n a list 
i n t he pr o d uct’s safet y re vie w pla n; ( 2) Tier 2 e ve nts are t h ose t hat 
are n ot Tier 1 b ut are c o nsi dere d “relati vely c o m m o n”; a Me d D R A 
preferre d ter m is defi ne d as a Tier 2 e ve nt if t here are 
 of 
partici pa nts i n at least 1 vacci ne gr o u p re p orti n g t he e ve nt; a n d 
( 3) Tier 3 e ve nts are t h ose t hat are neit her Tier 1 n or Tier 2 e ve nts. 
Descri pti ve s u m mar y  statistics (c o u nts a n d pr o p orti o ns) will be 
pr o vi de d f or Tier 3 e ve nts f or eac h vacci ne gr o u p. A nal ysis met h o ds 
are descri be d i n Secti o n 9. 3. 1. 1 .
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C C
I
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 5
9. 3. 3. Sec o n d ar y E n d p oi nt(s)/ Esti m a n d(s) A n al ysis
E n d p oi nt
St atistic al A n al ysis Met h o ds
Sec o n dar y  
efficac y 
( qIR V c o m pare d 
t o QI V a gai nst 
L C I or C CI 
ass ociate d wit h 
differe nt 
defi niti o ns of I LI
wit h partici pa nts 
1 8 t hr o u g h 
6 4 ye ars of a ge 
a n d ≥6 5 y ears of 
a ge)
T he a nal ys is of t he f oll o wi n g R V Es base d o n vari o us case defi niti o ns 
will use t he e xact c o n diti o nal bi n o mial met h o d, as descri be d f or t he 
a b o ve efficac y e n d p oi nt base d o n per- pr ot oc ol I LI. R V E will be 
esti mate d al o n g wit h 2 -si de d 9 5 % CI by a ge strat u m (partici pa nts 
1 8 t hr o u g h 6 4 a n d ≥6 5 years of a ge ).

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de LCI  cases wit h ass ociate d 
per -pr ot oc ol I LI ca use d b y all matc he d strai ns, wit h o nset at least 
1 4 da y s after vacci nati o n, i n t he qIR V gr o u p c o m pare d t o t he 
QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de LCI  cases wit h ass ociate d 
per - pr ot oc ol I LI ca use d b y eac h matc he d strai n, wit h o nset at least 
1 4 da y s after vacci nati o n, i n t he qIR V gr o u p c o m pare d t o t he 
QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de LCI  cases wit h ass ociated 
per -pr ot oc ol I LI ca use d b y all u nmatc he d strai n s, wit h o nset at least 
1 4 da y s after vacci nati o n, i n t he qIR V gr o u p c o m pare d t o t he 
QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de C CI cases ass ociate d wit h 
per -pr ot oc ol I LI ca use d b y a ny strai n, wit h o nset at least 1 4 da ys 
after vacci nati o n, i n t he qI R V gr o u p c o m pare d t o t he QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de LCI  cases ass ociate d wit h I LI 
(as defi ne d b y a p pl yi n g a m o difie d C D C defi niti o n) ca use d b y  a n y 
strai n, wit h o nset at least 1 4 da ys after vacci nati o n, i n t he 
qI R V gr o u p c o m pare d t o t he QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p or ti n g first-e pis o de LCI  cases ass ociate d wit h I LI 
(as defi ne d b y a p pl yi n g t he W H O defi niti o n) ca use d b y  a n y strai n, 
wit h o nset at least 1 4 da ys after vacci nati o n, i n t he qI R V gr o u p 
c o m pare d t o t he QI V gr o u p.

R V E, defi ne d as t he relati ve re d ucti o n of t he pr o p orti o n of 
partici pa nts re p orti n g first -e pis o de i nfl ue nza cases ass ociate d wit h 
I LI (
), 
wit h o nset at least 1 4 da ys after vacci nati o n, i n t he qI R V gr o u p 
c o m pare d t o t he QI V gr o u p.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 7
E n d p oi nt
St atistic al A n al ysis Met h o ds
Sec o n dar y  
i m m u n o ge nicity 
( partici pa nts
1 8 t hr o u g h 
6 4 ye ars of a ge 
a n d ≥6 5 y ears of 
a ge) 

H AI G M Ts a n d t heir ass ociate d 2 -si de d 9 5 % CIs will be pr o vi de d 
f or eac h strai n, by vacci ne gr o u p, at Da y 1 a n d 4 wee ks after recei pt 
of st u d y  i nter ve nti o n f or partici pa nt s e nr olle d i n t he n ort her n 
he mis p here a n d s o ut her n he mis p here, se paratel y, b y  a ge strat u m
( 1 8 thr o u g h 6 4 or ≥6 5 ye ars).

H AI G M F Rs fr o m bef ore vacci nati o n t o 4 wee ks after vacci nati o n 
a n d t heir ass ociate d 2 -si de d 9 5 % CIs will be pr o vi de d f or eac h 
strai n, f or partici pa nt s e nr olle d i n t he n ort her n he mis p here a n d 
s o ut her n he mis p here, se parately, b y  vacci ne gr o u p a n d a ge strat u m
( 1 8 thr o u g h 6 4 or ≥6 5 ye ars).

T he pr o p orti o n of partici pa nts ac hie vi n g H AI ser oc o n versi o n f or 
eac h strai n at 4 wee ks after vacci nati o n, t he pr o p orti o n of 
partici pa nts wit h H AI titers ≥1: 4 0 f or eac h strai n bef ore vacci nati o n 
a n d at 4 wee ks after vacci nati o n, a n d t heir ass ociate d 2-si de d 
Cl o p per -Pears o n 9 5 % CIs will be pr o vi de d f or partici pa nt s e nr olle d 
i n t he n ort her n he mis p here a n d s o ut her n he mis p here , se paratel y, b y  
vacci ne gr o u p a n d a ge strat u m ( 1 8 t hr o u g h 6 4 or ≥6 5 y ears).

T he pr o p orti o n of partici pa nts ac hie vi n g H AI ser oc o n versi o n f or all 
strai ns at 4 wee ks after vacci nati o n, t he pr o p orti o n of partici pa nts 
wit h H AI titers ≥1: 4 0 f or all strai ns bef ore vacci nati o n a n d at 
4 w ee ks after vacci nati o n, a n d t heir ass ociate d 2-si de d Cl o p per-
Pears o n 9 5 % CIs will be pr o vi de d f or partici pa nt s e nr olle d i n t he 
n ort her n he mis p here a n d s o ut her n he mis p here , se parately, b y  
vacci ne gr o u p a n d a ge strat u m ( 1 8 t hr o u g h 6 4 or ≥6 5 y ears).

T he a b o ve s u m mar y statistics will be pr o d uce d se paratel y f or 
a nti b o d y titers meas ure d b y
H AI s.
9. 3. 4. Terti ar y/ E x pl or at or y E n d p oi nt(s) A n al ysis
E n d p oi nt
St atistic al A n al ysis Met h o ds
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 8
E n d p oi nt
St atistic al A n al ysis Met h o ds
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 0 9
E n d p oi nt
St atistic al A n al ysis Met h o ds
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 1 0
E n d p oi nt
St atistic al A n al ysis Met h o ds
9. 3. 5. Ot her S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
A n y res ults fr o m i n vesti gati o n(s) ( E C G, tr o p o ni n le vel, car diac ec h ocar di o gra m, a n d/ or
car diac ma g netic res o na nce st u d y) t hat mi g ht b e i n dicati ve of m y ocar ditis or pericar ditis or 
a n A E SI wit hi n 1 4 d a y s after a st u d y vacci nati o n will als o be s u m marize d a n d liste d b y 
vacci ne gr o u p.
9. 4. I nteri m A n al yses
T here are n o f or mal i nteri m a nal y ses pla n ne d f or t his st u d y .
9. 5. A n al ysis Ti mi n g
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
Pri mar y  a nalys is f or t he y o u n ger a ge strat u m (partici pa nts 1 8 t hr o u g h 6 4 years of a ge ): 
A nal y sis of t he pri mar y efficac y a n d sec o n dar y i m m u n o ge nicity o bjecti ves will be c o n d ucte d 
w he n at least 
first-e pis o de e val ua ble L CI cases ass ociate d wit h per -pr ot oc ol I LI ca use d 
b y  a ny strai n ha ve bee n accr ue d .
Fi nal a nal ys is f or t he yo u n ger a ge strat u m ( partici pa nts 1 8 t hr o u g h 6 4 ye ars of a ge) : A nal ys is 
of t he efficac y , safet y, a n d i m m u n o ge nicit y o bjecti ves will be perf or me d f oll o wi n g 
c o m pleti o n of t he last visit of t he last partici pa nt i n t he st u d y. Ot her efficac y, safety, a n d 
i m m u n o ge nicity a nal ys is ma y be perf or me d bet wee n t he pri mar y  efficac y a n d fi nal a nal ys is
(Secti o n 6. 4. 3 ).
Pri mar y  a nalys is f or t he ol der a ge strat u m ( partici pa nts ≥6 5 y ears of a ge ): A nal y sis of t he 
pri mar y  efficac y, safet y, a n d sec o n dar y i m m u n o ge nicit y o bjecti ves m a y be c o n d ucte d w he n 
at least 
first-e pis o de e val ua ble L CI cases ass ociate d wit h per -pr ot oc ol I LI ca use d b y a n y 
strai n ha ve bee n accr ue d.
All V E esti mati o ns wit h a n y a d diti o nal LCI  cases c ollecte d after pri mar y a nal ysis f or eac h 
a ge strat u m will be descri pti vel y  s u m marize d.
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI
C CI
C CI

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 114
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 initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:
!
Providing written summaries of the status of the study to the IRB/EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/EC;
!
Notifying the IRB/EC of SAEs or other significant safety findings as required by IRB/EC 
procedures;
!
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 536/2014 for clinical 
studies, European MDR 2017/745 for clinical device research, 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.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 115
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 the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions regarding the 
study. The participant should be given sufficient time and opportunity to ask questions and to 
decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each participant is fully informed about the nature and 
objectives of the study, the sharing of data related to the study, and possible risks associated 
with participation, including the risks associated with the processing of the participant’s 
personal data.
The participant must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about their
right to access and correct their personal data and to withdraw consent for the processing of 
their personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 116
Participants must be reconsented to the most current version of the IRB/EC-approved ICD(s) 
during their participation in the study as required per local regulations.
A copy of the ICD(s) must be provided to the participant.
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 their 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.
Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access.
The sponsor maintains SOPs on how to respond in the event of unauthorized access, use, or 
disclosure of sponsor information or systems.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee 
This study will use an EDMC. The EDMC is independent of the study team and includes 
only external members. The EDMC charter describes the role of the EDMC in more detail.
090177e19dde1ccf\Approved\Approved On: 28-Jun-2023 12:29 (GMT)

PF-07252220 [Influenza modRNA Vaccine]
Protocol C4781004
Final Protocol Amendment 4, 27 June 2023
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 April 2022)
Page 117
The EDMC will be responsible for ongoing monitoring of the safety of participants in the 
study according to the charter. The recommendations made by the EDMC will be forwarded 
to the appropriate authorized Pfizer personnel for review and final decision. Pfizer will 
communicate such decisions, which may include summaries of aggregate analyses of 
endpoint events and of safety data that are not endpoints, to regulatory authorities and
investigators, as appropriate.
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/CTIS, and/or 
www.pfizer.com, and other public registries and websites in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT/CTIS
Pfizer posts clinical trial results on EudraCT/CTIS for Pfizer-sponsored interventional studies 
in accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts CSR synopses and plain-language study results summaries on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the corresponding study results 
are posted to www.clinicaltrials.gov. CSR synopses will have personally identifiable 
information anonymized.
Documents within marketing applications
Pfizer complies with applicable local laws/regulations to publish clinical documents included 
in marketing applications. Clinical documents include summary documents and CSRs 
including the protocol and protocol amendments, sample CRFs, and SAPs. Clinical 
documents will have personally identifiable information anonymized.
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Data sharing
Pfizer provides researchers secure access to participant-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. Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations. CSRs will have personally identifiable 
information anonymized.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.7. 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.
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the CSR.
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.
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Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
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 the Source 
Document Locator, 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.
The sponsor or designee will perform monitoring 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.
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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, including (but not limited to) 
regulatory authority decision, change in opinion of the IRB/EC, or change in benefit-risk 
assessment. Study sites will be closed upon study completion. A study site is considered 
closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:
!
Failure of the investigator to comply with the protocol, the requirements of the IRB/EC 
or local health authorities, the sponsor’s procedures, or the ICH GCP guidelines;
!
Inadequate recruitment of participants by the investigator;
!
Discontinuation of further study intervention development.
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
For multicenter trials, the primary publication will be a joint publication developed by the 
investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. 
The investigator agrees to refer to the primary publication in any subsequent publications. 
Pfizer will not provide any financial compensation for the investigator’s participation in the 
preparation of the primary congress abstract, poster, presentation, or primary manuscript for 
the study.
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Investigators are free to publish individual center results that they deem to be clinically 
meaningful after publication of the overall results of the study or 12 months after primary 
completion date or study completion at all sites, whichever occurs first, subject to the other 
requirements described in this section.
The investigator will provide Pfizer an opportunity to review any proposed publication or 
any other type of disclosure of the study results (collectively, “publication”) before it is 
submitted or otherwise disclosed and will submit all publications to Pfizer 30 days before 
submission. If any patent action is required to protect intellectual property rights, the 
investigator agrees to delay the disclosure for a period not to exceed an additional 60 days 
upon request from Pfizer. This allows Pfizer 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-intervention or Pfizer-related 
information necessary for the appropriate scientific presentation or understanding of the 
study results. For joint publications, should there be disagreement regarding interpretation 
and/or presentation of specific analysis results, resolution of, and responsibility for, such 
disagreements will be the collective responsibility of all authors of the publication.
For all publications relating to the study, the investigator and Pfizer will comply with 
recognized ethical standards concerning publications and authorship, including those 
established by the International Committee of Medical Journal Editors. The investigator will 
disclose any relationship with Pfizer and any relevant potential conflicts of interest, including 
any financial or personal relationship with Pfizer, in any publications. All authors will have 
access to the relevant statistical tables, figures, and reports (in their original format) required 
to develop the publication.
10.1.11. Sponsor’s Medically Qualified Individual
The contact information for the sponsor’s MQI for the study is documented in the study 
contact list located in the supporting study documentation/study portal or other electronic 
system.
To facilitate access to their investigator and the sponsor’s MQI for study-related medical 
questions or problems from nonstudy healthcare professionals, participants are provided with 
an 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 participant and their investigator and site staff, and between the investigator and 
sponsor study team. The ECC is only to be used by healthcare professionals not involved in 
the research study, as a means of reaching the investigator or site staff related to the care of a 
participant. The Pfizer Call Center number is to be used when the investigator and site staff 
are unavailable. The Pfizer Call Center number is not for use by the participant directly; if a 
participant calls that number directly, they will be directed back to the investigator site.
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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 nonpathogenic
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.
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10.3. Appendix 3: Contraceptive and Barrier Guidance 
10.3.1. 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 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):
!
Refrain from donating sperm.
PLUS either:
!
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent.
OR
!
Must agree to use contraception/barrier as detailed below:
!
Agree to use a male condom when having sexual intercourse with a WOCBP who is 
not currently pregnant.
OR
!
Be vasectomized, with the absence of sperm having been confirmed.
10.3.2. Female Participant Reproductive Inclusion Criteria
The criteria below are part of inclusion criterion 1 (Age and Sex; Section 5.1) and specify the 
reproductive requirements for including female participants. Refer to Section 10.3.4 for a 
complete list of contraceptive methods permitted in the study.
A female participant is eligible to participate if she is not pregnant or breastfeeding and at 
least 1 of the following conditions applies:
!
Is not a WOCBP (see definitions below in Section 10.3.3).
OR
!
Is a WOCBP and agrees to use an acceptable contraceptive method during the 
intervention period (for a minimum of 28 days after the last dose of study 
intervention). The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
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10.3.3. 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 a 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 of age and not using hormonal 
contraception or HRT.
!
A female on HRT and whose menopausal status is in doubt will be required to use 
one of the highly effective nonestrogen hormonal contraception methods if she
wishes to continue her HRT during the study. Otherwise, she must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
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10.3.4. 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.
The following contraceptive methods are appropriate for this study:
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.
5. Vasectomized partner:
!
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.
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Sexual Abstinence
8. 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.
Other Effective Methods
9. Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action.
10. Male or female condom, with or without spermicide.
11. Cervical cap, diaphragm, or sponge with spermicide.
12. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-Up 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.”
LFTs are not required as a routine safety monitoring procedure in this study. However, should 
an investigator deem it necessary to assess LFTs because a participant presents with clinical 
signs/symptoms, such LFT results should be managed and followed as described below.
In the majority of DILI cases, elevations in AST and/or ALT precede T bili elevations 
(>2 × ULN) by several days or weeks. The increase in T bili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and T bili values will be elevated within 
the same laboratory sample). In rare instances, by the time T bili 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 T bili 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 T bili baseline values within the normal range who 
subsequently present with AST OR ALT values ≥3 × ULN AND a T bili 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 T bili 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).
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!
Preexisting values of T bili above the normal range: T bili level increased from 
baseline value by an amount of ≥1 × ULN or if the value reaches ≥3 × ULN 
(whichever is smaller).
Rises in AST/ALT and T bili 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 T bili 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 
T bili 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: Kidney Safety Monitoring Guidelines
10.6.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney 
Injury
Standard kidney safety monitoring requires assessment of baseline and postbaseline serum
creatinine (Scr measurement to eGFR [Scr-based eGFR] or [eCrCl]). Baseline and 
postbaseline Scys makes it feasible to distinguish AKI from other causes of Scr increase. If 
Scr increase is confirmed after baseline, then reflex measurement of Scys is indicated to 
estimate the combined Scr-Scys eGFR calculation (for adults only).
Regardless of whether kidney function monitoring tests are required as a routine safety 
monitoring procedure in the study, if the investigator or sponsor deems it necessary to further 
assess kidney safety and quantify kidney function, then these test results should be managed 
and followed per standard of care.
10.6.2. Age-Specific Kidney Function Calculation Recommendations
10.6.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations
2021 CKD-EPI
Scr Only
Scr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation29
Female
if ≤ 0.7
N/A
eGFR = 143 × (Scr/0.7)-0.241  ×  (0.9938)Age
Female
if > 0.7
N/A
eGFR = 143 × (Scr/0.7)-1.200  ×  (0.9938)Age
Male
if ≤ 0.9
N/A
eGFR = 142 × (Scr/0.9)-0.302  ×  (0.9938)Age
Male
if > 0.9
N/A
eGFR = 142 × (Scr/0.9)-1.200  ×  (0.9938)Age
2021 CKD-EPI 
Scr-Scys 
Combined
Scr
(mg/dL)
Scys
(mg/L)
Recommended eGFR Equation29
Female
if ≤ 0.7
if ≤ 0.8
eGFR = 130 × (Scr/0.7)-0.219  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if ≤ 0.7
if > 0.8
eGFR = 130 × (Scr/0.7)-0.219  × (Scys/0.8)-0.778  × (0.9961)Age
Female
if > 0.7
if ≤ 0.8
eGFR = 130 × (Scr/0.7)-0.544  × (Scys/0.8)-0.323  × (0.9961)Age
Female
if > 0.7
if > 0.8
eGFR = 130 × (Scr/0.7)-0.544  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if ≤ 0.9
if ≤ 0.8
eGFR = 135 × (Scr/0.9)-0.144  × (Scys/0.8)-0.323  × (0.9961)Age
Male
if ≤ 0.9
if > 0.8
eGFR = 135 × (Scr/0.9)-0.144  × (Scys/0.8)-0.778  × (0.9961)Age
Male
if > 0.9
if ≤ 0.8
eGFR = 135 × (Scr/0.9)-0.544  ×  (Scys/0.8)-0.323  × (0.9961)Age
Male
if > 0.9
if > 0.8
eGFR = 135 × (Scr/0.9)-0.544  ×  (Scys/0.8)-0.778  × (0.9961)Age
10.6.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities
AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO
criteria.
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10.9. Appendix 9: Criteria for Allowing Inclusion of Participants With Chronic Stable 
HIV, HCV, or HBV Infection
Potential participants with chronic stable HIV, HCV, or HBV infection may be considered 
for inclusion if they fulfill the following respective criteria.
Known HIV infection
!
Confirmed stable HIV disease defined as documented viral load <50 copies/mL and 
CD4 count >200 cells/mm3 within 6 months before enrollment, and on stable 
antiretroviral therapy for at least 6 months.
!
If CD4 cell count 300-500/mm3 and HIV RNA suppressed for 2 years, CD4 cell 
count should have been obtained within 12 months of enrollment.
!
If CD4 cell count >500/mm3 and HIV RNA suppressed for 2 years, CD4 cell count 
measurement is optional.30
Known HCV infection
!
History of chronic HCV with evidence of sustained virological response (defined as 
undetectable HCV RNA) for ≥12 weeks following HCV treatment or without evidence of 
HCV RNA viremia (undetectable HCV viral load).
Known HBV infection
Confirmed inactive chronic HBV infection, defined as HBsAg present for ≥6 months and the 
following:
!
HBeAg negative, anti-HBe positive
!
Serum HBV DNA <2000 IU/mL
!
Persistently normal ALT and/or AST levels
!
In those who have had a liver biopsy performed, findings that confirm the absence of 
significant necroinflammation
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Amendment 2 (09 November 2022)
Overall Rationale for the Amendment:
Addition of a possible second influenza season in the study and to expand enrollment for the 
northern hemisphere 2022-2023 influenza season.
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
Throughout
Added clarifying 
terminology regarding
enrollment in the northern
and southern 
hemispheres.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season and to 
increase enrollment for the 
northern hemisphere 2022-2023 
influenza season.
Substantial.
1.1 Synopsis
Made updates to reflect 
the equivalent revisions in 
the body of the protocol.
Change in the study design to
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season and to 
increase enrollment for the 
northern hemisphere 2022-2023 
influenza season.
Substantial.
1.3 Schedule of Activities
For participants not 
included in the 
immunogenicity subset 
only, added the option for 
Visit 4 to be conducted as 
a telehealth visit.
To lessen the burden on sites and 
participants and aid in obtaining 
follow-up information 
expeditiously.
Substantial.
2.2.5 Clinical Overview
Specified the dose level of 
qIRV by age stratum.
Availability of Phase 2 safety 
and immunogenicity data.
Substantial.
2.3.1 Risk Assessment
Revised the interval 
between receipt of any 
mRNA-platform 
SARS-CoV-2 vaccine and 
study vaccination from 
28 days to 14 days.
To correct a typographical error
from the previous version of the 
protocol and to align with other
sections.
Nonsubstantial.
3 Objectives, Endpoints, 
and Estimands
Revised endpoints of 
secondary 
immunogenicity
objectives and added a 
new secondary objective.
Removed an exploratory 
objective and added 
2 new exploratory 
objectives.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season.
Substantial.
4.1 Overall Design
Revised to expand
enrollment in the northern 
hemisphere by 11,200
participants across both 
age strata, increasing total 
enrollment to 36,200 
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season and to 
increase enrollment for the 
Substantial.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
9.3.3 Secondary 
Endpoint(s)/Estimand(s) 
Analysis
Made updates to the 
secondary
immunogenicity 
objectives, and added a 
secondary efficacy 
objective and related 
analysis.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season.
Substantial.
9.3.4 Tertiary/Exploratory 
Endpoint(s)
Made updates to 
tertiary/exploratory 
objectives and related 
analysis.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season.
Substantial.
9.3.5 Other Safety 
Analyses
Corrected the window for 
reporting symptoms that 
might be indicative of 
myocarditis or pericarditis 
or an AESI from 4 weeks 
to 14 days after study 
vaccination.
Align with additional procedures 
for monitoring of potential 
myocarditis or pericarditis
detailed in Section 8.10.8.
Substantial.
9.5 Analysis Timing
Clarified timing of 
analysis.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season.
Substantial.
9.6.1 Relative Vaccine 
Efficacy
Made updates to reflect 
changes in sample size.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season and to 
increase enrollment for the 
northern hemisphere 2022-2023 
influenza season.
Substantial.
9.6.3 Safety
Made updates to Table 6
to reflect changes in 
sample size.
Change in the study design to 
potentially expand enrollment to 
the southern hemisphere for the 
2023 influenza season and to 
increase enrollment for the 
northern hemisphere 2022-2023 
influenza season.
Substantial.
Amendment 1 (28 July 2022)
Overall Rationale for the Amendment:
Change in the design to be powered to study efficacy in participants ≥18 years of age.
Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
1. Protocol Summary
Updates to reflect the 
equivalent revisions in the 
body of the protocol.
Change in the study design 
to be powered for efficacy.
Substantial.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
2.1. Study Rationale
Update to the rationale to 
include efficacy.
Change in the study design 
to be powered for efficacy.
Substantial.
2.2.1. Influenza
Addition of disease burden 
information for individuals
18 through 64 years of age.
As age group may now be 
included in the development 
plan.
Nonsubstantial.
2.2.5. Clinical Overview
Update to the design of 
C4781001 to reflect the 
latest protocol amendment.
Update to Phase 1/2 design
Substantial
2.3.1. Risk Assessment
Update to the risk profile of 
QIV using the package insert 
information from the 
standard-dose rather than 
high-dose QIV, given the 
likely comparator to be used 
in this age group.
Likely change to the 
comparator.
Substantial.
3. Objectives, Endpoints, 
and Estimands
Addition of primary and 
secondary efficacy 
objectives. Corresponding 
updates to other objectives.
Change in the study design 
to be powered for efficacy.
Substantial.
4.1. Study Design
Change in the design to be 
powered to study efficacy in 
participants ≥18 years of 
age, including update in the 
number of participants.
Change in the study design 
to be powered for efficacy.
Substantial.
4.3. Justification for Dose
Revised language pertaining 
to dose levels.
For clarity.
Substantial.
4.4. End of Study 
Definition
Revised to reflect the revised 
design.
Change in the study design 
to be powered for efficacy.
Substantial.
5.1. Inclusion Criteria
Removal of inclusion 
criterion 4.
To align with the internal 
protocol template.
Substantial.
5.2. Exclusion Criteria
Update to exclusion criterion 
9 to decrease the window in 
which a modRNA-platform 
SARS-CoV-2 vaccine may 
be administered.
To aid enrollment without 
compromising participants’ 
safety or compromising 
assessment of 
immunogenicity.
Substantial.
5.2. Exclusion Criteria
Update to exclusion 
criterion 10.
For clarity.
Substantial.
5.5. Criteria for 
Temporarily Delaying 
Enrollment/Randomizatio
n/Administration of Study 
Intervention
Decrease in the window in 
which nonstudy vaccinations 
may be administered relative 
to study intervention.
To aid enrollment without 
compromising participants’ 
safety or compromising 
assessment of 
immunogenicity.
Substantial.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
6.1. Study Intervention(s) 
Administered
Removal of the unit dose 
strength; no change to study 
interventions.
To allow flexibility based on 
Phase 1/2 data.
Substantial.
6.9.1. Prohibited During 
the Study
Decrease in the window in 
which nonstudy vaccinations 
may be administered relative 
to study intervention.
To aid enrollment without 
compromising participants’ 
safety or compromising 
assessment of 
immunogenicity.
Substantial.
8.1. Administrative 
Procedures
and 
8.2.2.
Immunogenicity 
Assessments
Add clarification that blood 
draws will be taken from 
participants in the 
immunogenicity subset.
Consistent with the revised 
study design.
Substantial.
8.3. Safety Assessments
and
8.3.4. Reactogenicity 
Electronic Diary
Add clarification that 
reactogenicity e-diaries will 
be used only in the 
reactogenicity subset.
Consistent with the revised 
study design.
Substantial.
8.3.5. Pregnancy Testing
Addition of this section and 
the requirement for all 
WOCBP to have a 
pregnancy test prior to 
vaccination.
Change in age group for the 
study.
Substantial.
8.4.1. Time Period and 
Frequency for Collecting 
AE and SAE Information
Updates to ensure 
consistency with 
Section 8.4.7.
Correct internal 
inconsistency in the 
document.
Substantial
8.10.2. Visit 1 –
Vaccination (Day 1)
and
8.10.4. Visit 3 – 4-Week 
Follow-Up Visit 
and
8.10.5. Visit 4 – 6-Month 
Follow-Up Visit (After 
Vaccination) – 175 to 
189 Days After Visit 1
Add clarification that blood 
draws will be taken from 
participants in the 
immunogenicity subset.
Consistent with the revised 
study design.
Substantial.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
8.10.2. Visit 1 –
Vaccination (Day 1)
and
8.10.3. Visit 2 – 1-Week 
Follow-Up Visit (After 
Vaccination)
and
8.10.4. Visit 3 – 4-Week 
Follow-Up Visit 
and
8.10.5. Visit 4 – 6-Month 
Follow-Up Visit (After 
Vaccination) – 175 to 
189 Days After Visit 1
and
8.10.7. Unscheduled Visit 
for a Grade 3 or 
Suspected Grade 4 
Reaction
Add clarification where 
necessary that procedures 
relating to the reactogenicity 
e-diary apply only to those in 
the reactogenicity subset.
Consistent with the revised 
study design.
Substantial.
8.10.8. Additional 
Procedures for 
Monitoring of Potential 
Myocarditis or 
Pericarditis
Revised procedures for 
monitoring of potential 
myocarditis or pericarditis 
(changes to symptom[s] 
window after vaccination 
and cardiologist evaluation).
To lessen the burden on sites 
and aid in obtaining 
follow-up information 
expeditiously.
Substantial.
9.1. Statistical Hypotheses
and
9.1.4. Multiplicity 
Adjustment
Updates to reflect a revised 
flexible hypothesis-testing 
approach.
Consistent with the revised 
study design.
Substantial.
9.1.3.1. Primary 
Estimands/Coprimary 
Estimands
and
9.3.2. Primary 
Endpoint(s)/Estimand(s) 
Analysis
Addition of a primary 
efficacy objective and 
related analysis.
Change in the study design 
to be powered for efficacy.
Substantial.
9.5. Analysis Timing
Updates to reflect alternative 
analysis timings based on 
whether a sufficient number 
of primary efficacy endpoint 
cases are accrued within the 
influenza season.
Change in the study design 
to be powered for efficacy.
Substantial.
9.6.1. Relative Vaccine 
Efficacy
Addition of this section to 
describe analyses to evaluate 
efficacy.
Change in the study design 
to be powered for efficacy.
Substantial.
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Section # and Name
Description of Change
Brief Rationale
Substantial or 
Nonsubstantial
9.6.2. Immunogenicity
Revised language to reflect 
the update in the study 
design such that all blood 
samples drawn will be 
assayed.
To reflect the revised study 
design.
Substantial.
9.6.3. Safety
Revised numbers provided in 
Table 6 to reflect the updated
sample size.
To reflect the revised study 
design.
Substantial.
10.3.1. Male Participant 
Reproductive Inclusion 
Criteria
Revised text to include 
vasectomy, with the absence 
of sperm having been 
confirmed, as an allowable 
form of contraception for 
male participants.
Change in age group for the 
study.
Substantial.
10.3.2. Female Participant 
Reproductive Inclusion 
Criteria
Add a requirement for 
WOCBP to use 
contraception.
Change in age group for the 
study.
Substantial.
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10.11. Appendix 11: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ADE
adverse device effect
AE
adverse event
AESI
adverse event of special interest
AKI
acute kidney injury
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AV
atrioventricular
BCR
breakpoint cluster region
bIRV
bivalent influenza modRNA vaccine
BLQ
below the limit of quantitation
BNT162b2
Pfizer’s COVID-19 vaccine
BUN
blood urea nitrogen
CBER
Center for Biologics Evaluation and Research
CCI
culture-confirmed influenza
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
computed tomography
CTIS
Clinical Trial Information System
DCT
data collection tool
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
emergency contact card
ECG
electrocardiogram
eCrCl
estimated creatinine clearance
eCRF
electronic case report form
EDB
exposure during breastfeeding
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Abbreviation
Term
e-diary
electronic diary
EDMC
external data monitoring committee
EDP
exposure during pregnancy
eGFR
estimated glomerular filtration rate
eSAE
electronic safety adverse event
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HA
hemagglutinin
HAI
hemagglutination inhibition assay
HBe
hepatitis B e
HBeAg
hepatitis B e antigen
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLA
human leukocyte antigen
HR
heart rate
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use
ID
identification
ILI
influenza-like illness
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IPAL
Investigational Product Accountability Log
IPM
investigational product manual
IRB
institutional review board
IRT
interactive response technology
ISO
International Organization for Standardization
IV
intravenous(ly)
KDIGO
Kidney Disease Improving Global Outcomes
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P F -0 7 2 5 2 2 2 0 [I nfl ue nza m o d R N A Vacci ne]
Pr ot oc ol C 4 7 8 1 0 0 4
Fi nal Pr ot oc ol A me n d me nt 4 , 2 7 J u ne 2 0 2 3
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 A pril 2 0 2 2)
Pa ge 1 5 9
A b bre vi ati o n
Ter m
L A I V
li ve atte n uate d i nfl ue nza vacci ne
L B B B
left b u n dle bra nc h bl oc k
L C I
la b orat or y-c o nfir me d i nfl ue nza
L F T
li ver f u ncti o n test
L L O Q
l o wer li mit of q ua ntitati o n
L N P
li pi d na n o particle
M C A R
missi n g c o m pletel y at ra n d o m
M D R
Me dical De vice Re g ulati o n
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
mI R V
m o n o vale nt i nfl ue nza m o d R N A vacci ne
mI T T
m o difie d i nte nt-t o-treat
m o d R N A
n ucle osi de -m o difie d messe n ger ri b o n ucleic aci d
M QI
me dicall y  q ualifie d i n di vi d ual
m R N A
messe n ger ri b o n ucleic aci d
N A
ne ura mi ni dase
N/ A
n ot a p plica ble
NI
n o ni nferi orit y
NI M P
n o ni n vesti gati o nal me dici nal pr o d uct
P F S
prefille d s yri n ge(s)
PI
pri nci pal i n vesti gat or
P P E
pers o nal pr otecti ve e q ui p me nt
P S S A
Pfizer ’s Seri o us A d verse E ve nt S u b missi o n Assista nt
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n
qI R V
q ua dri vale nt i nfl ue nza m o d R N A vacci ne
QI V
q ua dri vale nt i nfl ue nza vacci ne
Q Tc F
Q T i nter val c orrecte d b y t he Fri dericia f or m ula
Q T L
q ualit y  t olera nce li mit
R C D C
re verse c u m ulati ve distri b uti o n c ur ve
R N A
ri b o n ucleic aci d
R S V
res pirat or y sy n c ytial vir us
R T -P C R
re verse tra nscri pti o n –p ol y merase c hai n reacti o n
R V E
relati ve vacci ne efficac y
S A E
seri o us a d verse e ve nt
S A D E
seri o us a d verse de vice effect
S A P
statistical a nal ysis pla n
S A R S -C o V - 2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
Scr
ser u m creati ni ne
Sc y s
ser u m c ystati n C
S o A
sc he d ule of acti vities
0 9 0 1 7 7 e 1 9 d d e 1 c cf\ A p pr o v e d\ A p pr o v e d O n: 2 8- J u n- 2 0 2 3 1 2: 2 9 ( G M T)
C CI

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Abbreviation
Term
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBD
to be determined
T bili
total bilirubin
TCR
T-cell receptor
UADE
unanticipated (serious) adverse device effect
ULN
upper limit of normal
US
United States
USADE
unanticipated serious adverse device effect
USPI
United States package insert
VE
vaccine efficacy
WHO
World Health Organization
WOCBP
woman/women of childbearing potential
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11. REFERENCES
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Cowling BJ, Chan KH, Fang VJ, et al. Comparative epidemiology of pandemic and 
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Hall E. Influenza. Chapter 12. In: Centers for Disease Control and Prevention. Hall E, 
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Centers for Disease Control and Prevention. Estimated flu-related illnesses, medical 
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Cox NJ, Subbarao K. Influenza. Lancet. 1999;354(9186):1277-82.
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Grohskopf LA, Sokolow LZ, Olsen SJ, et al. Prevention and control of influenza with 
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Frey S, Vesikari T, Szymczakiewicz-Multanowska A, et al. Clinical efficacy of cell 
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Belshe RB. The need for quadrivalent vaccine against seasonal influenza. Vaccine.
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Bresee JS, Fry AM, Sambhara S, et al. Inactivated influenza vaccines. Chapter 31. In: 
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Co MDT, Orphin L, Cruz J, et al. In vitro evidence that commercial influenza vaccines 
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European Medicines Agency. Influenza vaccines - non-clinical and clinical module.
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US Food and Drug Administration. Guidance for industry: clinical data needed to 
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PF-07252220 [Influenza modRNA Vaccine]
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