A Phase II, Open-label Study to Assess the Safety and Immunogenicity of Fluzone® High-Dose Quadrivalent (Influenza Vaccine), 2021-2022 Formulation and a Third Dose of Moderna COVID-19 Vaccine (mRNA-1273 Vaccine) Administered Either Concomitantly or Singly in Adults 65 Years of Age and Older Previously Vaccinated With a 2-dose Schedule of Moderna COVID-19 Vaccine
Phase: PHASE2
Conditions: Influenza Immunization, Healthy Volunteers
Sponsor: Sanofi Pasteur, a Sanofi Company

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Title Page 
Protocol Title: 
A Phase II, open-label study to assess the safety and immunogenicity of Fluzone® High-Dose 
Quadrivalent (Influenza vaccine), 2021–2022 Formulation and a third dose of Moderna COVID-
19 Vaccine (mRNA-1273 vaccine) administered either concomitantly or singly in adults 65 years 
of age and older previously vaccinated with a 2-dose schedule of Moderna COVID-19 Vaccine  
Study Code: QHD00028 
Amendment Number: Amendment 2 
Compounds: Fluzone® High-Dose Quadrivalent (Influenza inactivated vaccine) (2021–2022 
Formulation)  
Moderna COVID-19 Vaccine (mRNA-1273 vaccine) 
Brief Title: 
Study of a Quadrivalent High-Dose Influenza Vaccine and a Moderna COVID-19 Vaccine 
administered either concomitantly or singly in participants 65 years of age and older previously 
vaccinated with a 2-dose schedule of Moderna COVID-19 Vaccine 
Study Phase: II 
Sponsor Name and Legal Registered Address: 
Sanofi Pasteur 
14 Espace Henry Vallée, 69007 Lyon, France 
Manufacturers:  
Fluzone High-Dose Quadrivalent (Influenza inactivated vaccine) 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
COVID-19 mRNA Vaccine 
Moderna US, Inc. 
200 Technology Sq, Cambridge, MA 02139 
Regulatory Agency Identifier Number(s): 
BB-IND: IND 017556 
WHO UTN: U1111-1266-7472 
Protocol Version Number: 4.0 
NCT04969276

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Approval Date: 19 July 2021 
Medical Monitor Name and Contact Information are provided in the Operating Guidelines. 
The study centers, the Investigators at each center, and the Coordinating Investigator(s) if any, are 
listed in a separate document. 
 
 

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Document History  
 
Previous 
Version 
Date 
Comments 
1.0 
10 June 2021 
Version not approved by the IEC/IRB 
2.0 
22 June 2021 
IEC/IRB-approved version not used in the study 
3.0 
01 July 2021 
First version used in the study 
* Versions in bold font have been approved by the IEC(s) / IRB(s) and used in the study. 
Overall Rationale for the Amendment: 
The main reason for updating protocol version 3.0 (Amendment 1) to protocol version 4.0 
(Amendment 2) was to add a 6-month safety follow-up phone call for all participants. 
 
 
 

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Table of Contents  
Document History ............................................................................................................................ 3 
List of Tables .................................................................................................................................... 8 
List of Figures .................................................................................................................................. 9 
1 
Protocol Summary ........................................................................................................... 10 
1.1 
Synopsis .......................................................................................................................... 10 
1.2 
Schema ............................................................................................................................ 13 
1.3 
Schedule of Activities (SoA) .......................................................................................... 14 
2 
Introduction ..................................................................................................................... 17 
2.1 
Study Rationale ............................................................................................................... 18 
2.2 
Background ..................................................................................................................... 18 
2.3 
Benefit/Risk Assessment ................................................................................................ 20 
2.3.1 
Risks from Study Participation ..................................................................................... 20 
2.3.2 
Benefits from Study Participation ................................................................................ 23 
2.3.3 
Overall Benefit-Risk Conclusion .................................................................................. 23 
3 
Objectives and Endpoints ............................................................................................... 23 
4 
Study Design .................................................................................................................... 24 
4.1 
Overall Design ................................................................................................................ 24 
4.2 
Scientific Rationale for Study Design ............................................................................. 25 
4.3 
Justification for Dose ...................................................................................................... 26 
4.4 
End of Study Definition .................................................................................................. 26 
5 
Study Population ............................................................................................................. 26 
5.1 
Inclusion Criteria ............................................................................................................ 26 
5.2 
Exclusion Criteria ........................................................................................................... 27 
5.3 
Lifestyle Considerations ................................................................................................. 28 
5.4 
Screen Failures ................................................................................................................ 29 
5.5 
Criteria for Temporarily Delaying Enrollment, Randomization, Administration of 
Study Intervention, or Blood Draws ............................................................................... 29 

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6 
Study Interventions and Concomitant Therapy ........................................................... 29 
6.1 
Study Interventions Administered .................................................................................. 29 
6.2 
Preparation/Handling/Storage/Accountability ................................................................ 31 
6.3 
Measures to Minimize Bias: Randomization and Blinding ............................................ 31 
6.3.1 
Randomization and Allocation Procedures .................................................................. 31 
6.3.2 
Blinding and Code-breaking Procedures ...................................................................... 32 
6.4 
Study Intervention Compliance ...................................................................................... 32 
6.5 
Dose Modification .......................................................................................................... 32 
6.6 
Continued Access to Study Intervention After the End of the Study ............................. 32 
6.7 
Treatment of Overdose.................................................................................................... 32 
6.8 
Concomitant Therapy ...................................................................................................... 33 
6.8.1 
Rescue Medicine ........................................................................................................... 33 
7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal .......................................................................................... 34 
7.1 
Discontinuation of Study Intervention ............................................................................ 34 
7.2 
Participant Discontinuation/Withdrawal from the Study ................................................ 34 
7.3 
Lost to Follow-up ............................................................................................................ 34 
8 
Study Assessments and Procedures ............................................................................... 35 
8.1 
Efficacy and Immunogenicity Assessments ................................................................... 36 
8.1.1 
Efficacy Assessments ................................................................................................... 36 
8.1.2 
Immunogenicity Assessments ...................................................................................... 36 
8.1.2.1 
Immunogenicity Assessments Related to Fluzone High-Dose Quadrivalent 
Administration ............................................................................................................ 36 
8.1.2.2 
Immunogenicity Assessments Related to Moderna COVID-19 Vaccine 
Administration ............................................................................................................ 37 
8.2 
Safety Assessments ......................................................................................................... 37 
8.2.1 
Medical History ............................................................................................................ 37 
8.2.2 
Physical Examinations .................................................................................................. 38 
8.2.3 
Vital Signs .................................................................................................................... 38 
8.3 
Adverse Events (AEs), Serious Adverse Events, and Other Safety Reporting............... 38 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information ......................... 38 
8.3.2 
Method of Detecting AEs and SAEs ............................................................................ 39 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................ 40 
8.3.4 
Regulatory Reporting Requirements for SAEs ............................................................ 40 
8.3.5 
Pregnancy ..................................................................................................................... 40 
8.3.6 
Adverse Events of Special Interest ............................................................................... 40 
8.3.7 
Medically Attended Adverse Events ............................................................................ 43 

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8.4 
Pharmacokinetics ............................................................................................................ 43 
8.5 
Genetics ........................................................................................................................... 43 
8.6 
Biomarkers ...................................................................................................................... 43 
8.7 
Immunogenicity Assessments ......................................................................................... 43 
8.8 
Medical Resource Utilization and Health Economics .................................................... 43 
8.9 
Leftover Biological Samples and Use of Data ................................................................ 43 
9 
Statistical Considerations ............................................................................................... 45 
9.1 
Statistical Hypotheses ..................................................................................................... 45 
9.2 
Sample Size Determination ............................................................................................. 45 
9.3 
Analysis Sets ................................................................................................................... 45 
9.4 
Statistical Analyses ......................................................................................................... 45 
9.4.1 
General Considerations ................................................................................................. 46 
9.4.2 
Study Endpoints ............................................................................................................ 46 
9.4.3 
Other Analysis .............................................................................................................. 46 
9.5 
Interim Analyses ............................................................................................................. 46 
10 
Supporting Documentation and Operational Considerations .................................... 47 
10.1 
Appendix: Regulatory, Ethical, and Study Oversight Considerations ............................ 47 
10.1.1 
Regulatory and Ethical Considerations ........................................................................ 47 
10.1.2 
Financial Disclosure ..................................................................................................... 48 
10.1.3 
Informed Consent Process ............................................................................................ 48 
10.1.4 
Data Protection ............................................................................................................. 49 
10.1.5 
Dissemination of Clinical Study Data .......................................................................... 51 
10.1.6 
Data Quality Assurance ................................................................................................ 52 
10.1.7 
Source Documents ........................................................................................................ 52 
10.1.8 
Study and Site Start and Closure .................................................................................. 53 
10.1.9 
Publication Policy ......................................................................................................... 54 
10.2 
Appendix: AEs and SAEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ............................................................................................... 54 
10.2.1 
Definition of AE ........................................................................................................... 54 
10.2.2 
Definition of SAE ......................................................................................................... 57 
10.2.3 
Recording and Follow-Up of AE and/or SAE .............................................................. 58 
10.2.4 
Reporting of SAEs ........................................................................................................ 60 
10.2.5 
Assessment of Intensity ................................................................................................ 61 
10.2.5.1 
Tables for Clinical Abnormalities .............................................................................. 61 
10.2.5.1.1 
Solicited AR Intensity Grading Scale ...................................................................... 61 
10.2.5.1.2 
Unsolicited AE Intensity Grading Scale .................................................................. 66 
10.3 
Appendix: Risk-based Approach .................................................................................... 67 

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10.4 
Appendix: Abbreviations ................................................................................................ 68 
10.5 
Appendix: Protocol Amendment/Update History ........................................................... 70 
11 
References ........................................................................................................................ 71 
12 
Sponsor Signature Page .................................................................................................. 74 
 
 
 
 

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List of Tables  
Table 1.1: Schedule of activities ................................................................................................... 15 
Table 2.1: Potential risks of clinical significance and risk management ...................................... 20 
Table 3.1: Objectives and endpoints ............................................................................................. 23 
Table 4.1: Overall design .............................................................................................................. 25 
Table 6.1: Identity of study interventions ...................................................................................... 29 
Table 6.2: Arms and Associated Study Interventions ................................................................... 31 
Table 8.1: Blood sampling volume (mL) per visit ........................................................................ 35 
Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales – 
Adults ............................................................................................................................................ 62 
Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales – 
Adults ............................................................................................................................................ 64 
 
 
 
 

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List of Figures  
Figure 1.1 – Graphical study design .............................................................................................. 14 
 
 
 
 

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Brief Summary: 
The main purpose of this Phase II study is to assess the safety and immunogenicity of a dose of 
Fluzone High-Dose Quadrivalent vaccine and a third dose or booster dose of Moderna COVID-19 
Vaccine administered concomitantly or singly in adults 65 years of age and older having received 
their second dose of the 2-dose schedule of Moderna COVID-19 Vaccine at least 5 months before 
enrollment in the study. 
Study Duration: 6 months (approximately 180 days) 
Visit Frequency: 2 visits (ie, a visit on D01 and D22) and 2 telephone contacts (ie, on D08 and 
D181) 
Condition/Diseases: influenza, COVID-19 disease 
Study Hypothesis: 
This will be a descriptive study. No hypothesis will be tested. 
Health Measurement/Observation: 
The study will assess whether the concomitant administrations of Fluzone High-Dose 
Quadrivalent vaccine and Moderna COVID-19 Vaccine is safe, well tolerated, and immunogenic. 
Number of Participants: 
A total of 300 participants (approximately 100 participants in each arm) are planned to be 
enrolled. 
Intervention Groups and Duration: 
Eligible participants will be randomized in a 1:1:1 ratio corresponding to i) concomitant 
administration of Fluzone High-Dose Quadrivalent and COVID-19 mRNA Vaccine, 
ii) administration of Fluzone High-Dose Quadrivalent alone, and iii) administration of COVID-19 
mRNA Vaccine alone. 
Participants will be in the Active Phase from enrollment (Day 1 [D01]) until completion of Visit 2 
(V02) and in the 6-Month Safety Follow-Up from completion of V02 until approximately 
6 months after V01. Participants will thus be in the study for approximately 180 days.  
Study intervention(s) 
Investigational medicinal product 1: Fluzone High-Dose Quadrivalent vaccine (0.7 mL dose), 
2021–2022 formulation for the Northern Hemisphere (NH) influenza season. 
• Form: Sterile suspension for injection in a pre-filled syringe 
• Composition: 60 mcg of HA of each of the following strains: 
- 
A/Victoria/2570/2019 IVR-215 (H1N1) 
- 
A/Tasmania/503/2020 IVR-221 (an A/Cambodia/e0826360/2020-like virus) (H3N2) 
- 
B/Phuket/3073/2013 (B Yamagata lineage) 

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- 
B/Washington/02/2019 (B Victoria lineage) 
• Route of administration: intramuscular (IM) 
Investigational medicinal product 2: Moderna COVID-19 Vaccine (mRNA-1273 vaccine) 
• Form: Sterile suspension (white to off-white) in multidose vial 
• Composition: 100 mcg of mRNA (formulated in SM-102 lipid nanoparticles) 
• Route of administration: IM 
Statistical Considerations: 
Analyses of Study Objectives will be descriptive. Endpoints will be summarized and for the main 
parameters; 95% CIs for the point estimates will be calculated using the normal approximation 
after log transformation for quantitative data (eg. GMTs and GM of individual ratios) and exact 
binomial distribution (Clopper-Pearson method, quoted by Newcombe) for single proportions. 
Safety Objective 
For safety analyses the safety analysis set (SafAS) will be used. Results will be presented by actual 
study group and vaccine received. 
Immunogenicity Objectives 
For immunogenicity analyses the Immunogenicity analysis set (IAS) will be used. Results will be 
presented for each timepoint by actual study group and vaccine received. 
In addition, the ratios of post-vaccination GMTs between concomitant and single injections will 
be presented for the five antigens with 2-sided 95% CIs. 
Data Monitoring/Other Committee: No 
1.2 
Schema  
The graphical design of QHD00028 study is presented in Figure 1.1. 

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Figure 1.1 – Graphical study design  
 
1.3 
Schedule of Activities (SoA)  
The study Schedule of Activities (SoA) for all 3 treatment groups is presented in Table 1.1.  
Visit procedures are detailed in the Operating Guidelines. 
 

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Table 1.1: Schedule of activities  
Phase II Study, 2 Visits, 2 Telephone Contacts, either 1 or 2 Vaccination, 2 Blood Samples, 
180 Days’ Duration Per Participant 
Visit (V) / Telephone Contact (TC) 
Collection of 
information 
in the CRF 
V01 
TC1 
V02 
TC2 
6-Month Safety 
Follow-up 
Study timelines (days [D]) 
 
D01 
D08 
D22 
D181 
Time interval (days) 
 
 
V01 + 
7 days 
V01 + 
21 days 
V01 +  
180 days 
Time windows (days)  
 
 
[+2 days] 
[+3 days] 
[+14 days] 
Visit procedures: 
 
 
 
 
 
Informed consent 
X 
X 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
Collection of demographic data 
X 
X 
 
 
 
Collection of medical history * 
X 
Significant 
Medical 
History 
X 
 
 
 
History of seasonal influenza and 
COVID-19 vaccination 
X 
X 
 
 
 
Physical examination † 
 
X 
 
 
 
Pre-vaccination temperature 
 
X 
 
 
 
Randomization / Allocation of 
participant number 
X 
X 
 
 
 
Blood samples (BL) for Ab assays (20 
mL) ‡ 
X 
BL0001 
 
BL0002 
 
Vaccination (VAC) 
X 
VAC1 
(all groups) 
VAC2 
(Group 1) 
 
 
 
Immediate surveillance (30 min) 
X 
X 
 
 
 
Diary card (DC) provided 
 
DC1§ 
 
 
 
DC reviewed 
 
 
DC1** 
 
 
DC collected 
 
 
 
DC1†† 
 
Memory Aid (MA) provided 
 
 
 
X 
 
MA reviewed 
 
 
 
 
X 
Collection of solicited injection site 
and systemic reactions 
X 
Up to 7 days after 
vaccination 
 
 
Collection of unsolicited AEs 
X 
Up to 21 days after vaccination 
 
Collection of concomitant medications 
X 
Reportable 
concomitant 
medication 
X 
 
X 
 
Telephone contact 
 
 
X 
 
X‡‡ 
Collection of SAEs, AESIs, and 
MAAEs §§ 
X 
To be reported at any time during the study 
End of Active Phase participation 
record *** 
X 
 
 
X 
 
End of 6-month safety follow-up *** 
 
 
 
 
X 

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Abbreviations: Ab, antibody; AE, adverse event; AESI, adverse event of special interest; BL, blood sample (#); 
CRF, case report form; D, Day; DC, diary card; SAE, serious adverse event; ; MAAE, medically-attended adverse 
event; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; V, Visit; VAC, Vaccination; MA, Memory 
Aid. 
*       Including history of COVID-19 infection. 
†      Targeted physical examination will be performed at V01. If needed, targeted physical examination based on 
medical history and Investigator’s discretion might be performed at the other vaccination visit(s).  
‡     BL0001 must be collected before vaccine injection. Participants that consent to Future Research by ticking the 
corresponding box in the ICF will provide a 20 mL of blood instead of 10 mL for each BL0001 and BL0002. 
§     Participants will use DC1 to record information about solicited reactions, unsolicited AEs, SAEs, and AESIs 
from D01 to D08 after vaccination and will continue to record information about unsolicited AEs, SAEs, and 
AESIs from D09 to D22. 
**    The Investigator or an authorized designee will remind the participants to bring back the DC at the next visit and 
will answer any questions. 
††   The Investigator or an authorized designee will interview the participants to collect the information recorded 
in the DC1 and will attempt to clarify anything that is incomplete or unclear. 
‡‡   During this call the staff will review the MA with the subject and determine whether the subject experienced 
any SAE, AESI or MAAEs not yet reported. 
§§   AESIs (serious and non-serious) will be collected throughout the study as SAEs to ensure that events are 
communicated to the Sponsor in an expedited manner and followed up until the end of the follow-up period 
or resolution, as per the assigned causal relationship. Full list of AESIs is available in Section 8.3.6. 
***   Participants will be in the Active Phase from enrollment (D01) until completion of V02 and in the 6-Month 
Safety Follow-Up from completion of V02 until approximately 6 months after V01. 
 

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2 
Introduction  
Fluzone® High-Dose Quadrivalent (Influenza Vaccine)  
Fluzone High-Dose Quadrivalent vaccine is an inactivated influenza vaccine containing 60 mcg of 
hemagglutinin (HA) of each of the A strains (A/H1N1 and A/H3N2) and of each of the B strains 
(from the Victoria lineage and from the Yamagata lineage), in compliance with the seasonal 
influenza World Health Organization (WHO). A recent systematic review and meta-analysis, 
including over 34 million participants and over 10 influenza seasons, showed that irrespective of 
circulating strain and antigenic match, the high-dose inactivated trivalent influenza vaccine is 
more effective than standard-dose vaccine in preventing both influenza-like illness and influenza-
related hospitalizations in both controlled and real-world conditions (1). Fluzone High-Dose 
Quadrivalent vaccine is indicated for active immunization for the prevention of influenza in 
persons 65 years of age and older. 
Moderna COVID-19 Vaccine (mRNA-1273 vaccine) 
An outbreak of severe respiratory illnesses in Wuhan City, Hubei Province, China in 
December 2019 heralded the appearance of a novel coronavirus, severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2), in the human population. The rapid escalation of the 
outbreak led to a declaration by the WHO on 20 January 2020 of a Public Health Emergency of 
International Concern, followed by the declaration on 11 March 2020 of a pandemic (2). As of 
21 June 2021, the virus has infected over 178 million individuals (3). A number of vaccine 
candidates are in clinical development including messenger RNA (mRNA) encoding the Spike (S) 
protein of SARS-CoV-2 that induce neutralizing antibodies.  
The development of an RNA-based vaccine encoding a viral antigen, which is then expressed by 
the vaccine recipient as a protein capable of eliciting protective immune responses, provides 
significant advantages over more traditional vaccine approaches. Unlike live attenuated vaccines, 
RNA vaccines may be given to people who cannot be administered live virus. At this stage of its 
characterization, there is a positive benefit/risk in administering the vaccine during pregnancy. 
RNA-based vaccines are manufactured via a cell-free in vitro transcription process, which allows 
an easy and rapid production and the prospect of producing high numbers of vaccination doses 
within a shorter time period than achieved with traditional vaccine approaches. This capability is 
pivotal to enable the most effective response in outbreak scenarios. 
Moderna COVID-19 Vaccine is a lipid-nanoparticle (LNP) –encapsulated mRNA vaccine 
expressing the prefusion-stabilized spike glycoprotein, that was developed by Moderna and the 
Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), 
within the National Institutes of Health (NIH) (4). Emergency authorization or other forms of 
regulatory approval have been granted in multiple countries for this vaccine. 
Under the current Emergency Use Authorization, Moderna COVID-19 Vaccine is currently used 
for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of 
age and older. The clinical efficacy of Moderna COVID–19 Vaccine is based on an ongoing 
Phase III randomized, placebo-controlled, observer-blind clinical trial conducted in adults aged 
18 years and older. Vaccine efficacy of 94.1% (95% confidence interval of 89.3% to 96.8%) was 

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demonstrated with a median length of follow up for efficacy for participants in the study of 9 
weeks post Dose 2 (5).  
The safety Moderna COVID-19 Vaccine was evaluated in an ongoing Phase III involving 
30 351 participants who received at least one dose of Moderna COVID-19 Vaccine or placebo. 
Overall, the vaccine was well tolerated. Moderate, transient reactogenicity after vaccination 
occurred more frequently in the Moderna COVID-19 Vaccine group. Serious adverse events were 
rare and incidence was similar in the two groups (5). Moderna COVID-19 Vaccine has been 
registered in multiple countries and has been administered to millions of vaccine recipients. 
In May 2020, Moderna initiated a 3-part Phase IIa study in which 60 participants having 
previously received a 2-dose schedule of Moderna COVID-19 Vaccine (either 50 mcg or 100 mcg 
of mRNA-1273) received a 20 mcg of mRNA-1273.351 booster dose, a 50 mcg of mRNA-
1273.351 booster dose, or a 50 mcg of mRNA-1273/mRNA-1273.351 mixture booster dose are 
evaluated (6). In May 2021, Moderna reported initial data demonstrating that a single booster dose 
of its COVID-19 vaccines, mRNA-1273 or mRNA-1273.351, enhanced neutralizing antibody 
(Ab) titer responses in previously vaccinated people (7). 
2.1 
Study Rationale  
This study will evaluate the safety and immunogenicity of Fluzone High-Dose Quadrivalent 
vaccine and of a third or “booster” dose of Moderna COVID-19 Vaccine administered 
concomitantly or singly in different treatment groups. Participants in this study will be 65 years of 
age and older and will have received their second dose of the 2-dose schedule of Moderna 
COVID-19 Vaccine at least 5 months before enrollment in the study.  
The concomitant administration of Fluzone High-Dose Quadrivalent vaccine with a dose of 
Moderna COVID-19 Vaccine has the potential to ease the implementation of national 
immunization programs both by shortening the overall period during which vaccination takes 
place and by reducing the number of visits to health care providers. 
2.2 
Background  
Influenza disease 
Influenza is a contagious, acute virus respiratory disease. It is typically characterized by the rapid 
onset of fever, myalgia, sore throat, and non-productive cough. Influenza can cause severe 
malaise, which lasts for several days. While influenza affects all age groups, the very young, older 
adults, and persons with underlying health problems are at increased risk for complications. 
Members of high-risk groups who become ill with influenza are more likely than the general 
population to require hospitalizations (8). 
Influenza in humans can be caused by influenza type A and type B viruses belonging to the genus 
Orthomyxoviridae and characterized as enveloped, negative strand, segmented ribonucleic acid 
viruses. The virus envelope contains 2 virus-coded glycoprotein spikes, the HA and 
neuraminidase proteins, key antigens in the host response to influenza virus in both natural 
infection and vaccination. 

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Although influenza A accounts for the majority of circulating viruses in most countries and 
seasons, influenza B circulates every year, late in the season in comparison to influenza A viruses, 
and accounts for 20% of all influenza isolates worldwide since 2000 (9). In general, the burden of 
disease from influenza B is less than that from A/H3N2 but greater than A/H1N1 (10). 
Vaccination with influenza vaccine is the primary method for preventing influenza and its severe 
complications. It has been shown to be effective in reducing influenza-associated morbidity and 
mortality in groups at increased risk for influenza-related complications such as infants and young 
children and persons 50 years of age and older. Of note, immune responses to the vaccine are 
lower in seniors than those in young healthy adults (11). Strategies to improve immune responses 
to the vaccine in the elderly population could provide substantial additional reductions in 
influenza-associated morbidity and mortality. One approach is to increase the dose of HA in 
inactivated vaccines. Previous studies evaluating the immune responses in terms of 
hemagglutination inhibition (HAI) antibodies with higher doses of HA per strain in different 
influenza vaccines support a dose-response effect (12). 
Fluzone High-Dose Quadrivalent vaccine was developed for use in the elderly against influenza 
through the use of higher antigen content, with the goal of providing older adults with improved 
protection against the disease. 
Fluzone High-Dose Quadrivalent vaccine belongs to the pharmacotherapeutic group of viral 
influenza vaccines. A detailed description of the chemistry, pharmacology, efficacy, and safety of 
Fluzone High-Dose Quadrivalent vaccine is provided in the prescribing information (13). 
COVID-19 disease 
SARS-CoV-2 is a novel coronavirus that emerged in the human population and has led to a 
pandemic of acute respiratory disease named COVID-19. The clinical profile of COVID-19, the 
illness caused by SARS-CoV-2, is variable (14). In the majority of cases, the manifestations are 
mild, or individuals may be asymptomatic (15). Among those with symptoms, typical 
presentations include fever, cough, and shortness of breath. More severe manifestations include 
acute hypoxemic respiratory failure requiring intubation and mechanical ventilation, in some 
cases resulting in death. While mostly self-limited, symptoms such as fatigue and dyspnea appear 
to persist for up to 2 months after illness onset despite viral clearance (16). Based on early data, 
adults over 50 years of age and individuals with chronic medical conditions are at a higher risk of 
severe outcomes and death (15) (17). 
The burden of SARS-CoV-2 morbidity and mortality has been catastrophic with greater than 
3.8 million deaths recorded since first emerging in December 2019 among over 178 million 
confirmed cases (as of 21 June 2021) (3). In many locations, the rapid emergence of COVID-19 
has overwhelmed the capacity of health systems to provide care for COVID-19-affected patients, 
let alone unaffected patients. Interventions to reduce transmission through reduction of population 
contact (also called social distancing) has had profound economic consequences. Safe and 
effective vaccines with sufficient doses would be vital to address the significant medical and 
societal burden caused by the pandemic. 
Moderna COVID-19 Vaccine belongs to the pharmacotherapeutic group of “other viral vaccines”. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Risk Management 
age: malaise, myalgia, and 
headache 
A Phase III study performed in 
persons ≥ 65 years of age 
demonstrated increased rates of 
solicited systemic reactions in 
participants receiving Fluzone 
High-Dose vaccine compared to 
persons receiving Fluzone 
vaccine but were typically mild 
and transient (18). Placebo-
controlled trials suggest that in 
elderly persons and in healthy 
young adults, split-virus 
influenza vaccine is not 
associated with higher rates of 
systemic symptoms when 
compared with placebo injection 
(19). Safety monitoring of 
Fluzone High-Dose vaccine 
during the first year after 
licensure indicated a higher than 
expected number of 
gastrointestinal events compared 
with standard-dose vaccine, but 
otherwise no new safety 
concerns were identified (20). 
informed of these potential 
reactions, the need to attend the 
clinic if they are unwell, and the 
possibility to take 
analgesic / antipyretic drug 
Immediate allergic reactions 
Immediate allergic reactions (eg, 
hives, angioedema, allergic 
asthma, and systemic 
anaphylaxis) occur rarely after 
influenza vaccination. These 
reactions probably result from 
hypersensitivity to some vaccine 
component (21) (22) (23). 
These types of reactions are 
exceedingly rare and would most 
likely occur in persons with a 
severe reaction to influenza 
vaccine in the past. Vaccine 
should not be administered to 
anyone who has had a severe 
allergic reaction to any 
component of the vaccine. 
Exclusion criterion E02 for those 
at increased risk 
Observation period (30 min) 
after vaccination for early 
detection and treatment 
Addressed in IB (administration 
precautions, potential AEs) 
Guillain-Barré syndrome 
Among persons who received 
the swine influenza vaccine in 
During the informed consent 
process, the participants 

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The present study will investigate the safety and immunogenicity of Fluzone High-Dose 
Quadrivalent vaccine and a third/booster dose of Moderna COVID-19 Vaccine when administered 
concomitantly or singly in adults 65 years of age and older in the US. 
4.3 
Justification for Dose  
A single dose of Fluzone High-Dose Quadrivalent vaccine is indicated for individuals 65 years of 
age and older to give protection against influenza.  
So far, the safety and efficacy of Moderna COVID-19 Vaccine has been shown when the vaccine 
is administered as a course of 2 doses at least 28 days apart. However, repeated vaccination with a 
single dose of Moderna COVID-19 Vaccine (third or booster dose) is currently under evaluation 
in clinical studies and may be recommended. Although the Advisory Committee on Immunization 
Practices (ACIP) does not currently provide guidance for a booster (third) dose, adults 65 years of 
age and older are at the highest risk for COVID-19 and related complications and thus more likely 
to be prioritized in the event a third dose is recommended. 
Therefore, participants in this study will be administered a dose of Fluzone High-Dose 
Quadrivalent vaccine and a dose of Moderna COVID-19 Vaccine either concomitantly or singly. 
4.4 
End of Study Definition  
A participant is considered to have completed the Active Phase if he/she completed V02. 
Likewise, a participant is considered to have completed the 6-month safety follow-up if he/she 
completed the 6-month telephone contact planned in the SoA. 
The end of the study is defined as the date of the last contact of the last participant in the study. 
However, for periodic safety reports, the study is considered completed when the clinical study 
report is finalized. 
5 
Study Population  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria  
Participants are eligible for the study only if all of the following criteria are met: 
Age 
I01: 
Aged ≥ 65 years of age on the day of inclusiona. 
Type of participant and disease characteristics 
                                                 
a  “≥ 65 years” means from the day of the 65th birthday onwards. 

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I02: 
In good health or with underlying medical condition(s) that are judged to be stable by the 
Investigator. A stable medical condition is defined as disease not requiring significant 
change in therapy or hospitalization for worsening disease during the 3 months before 
enrollment. 
I03: 
Participants who previously received 2 injections of Moderna COVID-19 Vaccine with the 
second dose received at least 5 months before V01a. 
Informed Consent 
I04: 
Informed consent form has been signed and dated. 
Other Inclusions 
I05: 
Able to attend all scheduled visits and to comply with all study procedures. 
5.2 
Exclusion Criteria  
Participants are not eligible for the study if any of the following criteria are met: 
Medical conditions 
E01: Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, 
within the preceding 6 months; or long-term systemic corticosteroid therapy 
(prednisone or equivalent for more than 2 consecutive weeks within the 3 months 
preceding planned inclusion) 
E02: 
Known systemic hypersensitivity to any of the study intervention components, or history 
of a life-threatening reaction to the study interventions used in the study or to a product 
containing any of the same substancesb 
E03: 
Previous dermal filler injection (either lips or face fillers) 
E04: Thrombocytopenia, contraindicating IM injection 
E05: 
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 
contraindicating IM vaccination. 
E06: 
Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere 
with study conduct or completion.c 
E07: 
Moderate or severe acute illness/infection (according to Investigator judgment) on the day 
of study intervention administration or febrile illness (temperature ≥ 100.4°F [38.0°C]). A 
                                                 
a  Confirmation of receipt of the 2-dose schedule of Moderna COVID-19 Vaccine will be documented by capturing 
the date and lot number of the second Moderna COVID-19 Vaccine injection in source document. 
b  The components of study interventions are listed in the Prescribing Information for the Fluzone High-Dose 
Quadrivalent vaccine and in the Investigator’s Brochure for the Moderna COVID-19 Vaccine. 
c  Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, autoimmune disorders, 
diabetes, psychomotor diseases, and known congenital or genetic diseases. 

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prospective participant should not be included in the study until the condition has resolved 
or the febrile event has subsided 
E08: 
Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, 
might interfere with the study conduct or completion 
E09: 
History of serious adverse reaction to any influenza or COVID-19 vaccines 
E10: 
Personal history of Guillain-Barré syndrome (GBS) 
E11: 
Any condition that in the opinion of the Investigator would pose a health risk to the 
participant if enrolled or could interfere with the evaluation of the vaccine 
E12: Personal history of clinically significant developmental delay (at the discretion of the 
Investigator), neurologic disorder, or seizure disorder 
E13: Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C 
Prior/concomitant therapy 
E14: Receipt of any vaccine in the 4 weeks preceding the study intervention(s) 
administration or planned receipt of any vaccine in the period between V01 and 
4 weeks following the study intervention(s) administrationa 
E15: 
Receipt of blood-derived immune globulins, blood, or blood-derived products in the past 3 
months 
Prior/concurrent clinical study experience 
E16: Participation at the time of study enrollment (or in the 30 days preceding the first study 
vaccination) or planned participation during the present study period in another clinical 
study investigating vaccine, drug, medical device, or medical procedure 
Other exclusions 
E17: 
Deprived of freedom by an administrative or court order, or in an emergency setting, or 
hospitalized involuntarily 
E18: 
Identified as an Investigator or employee of the Investigator or study center with direct 
involvement in the proposed study, or identified as an immediate family member (ie, 
parent, spouse, natural or adopted child) of the Investigator or employee with direct 
involvement in the proposed study 
5.3 
Lifestyle Considerations  
No other restrictions than the ones listed in the exclusion criteria or in the contraindications for 
subsequent vaccinations are required. 
                                                 
a    It is to be noted that vaccination with Fluzone High-Dose Quadrivalent vaccine offered to Group 3 participants at 
the end of the Active Phase (V02) will not be considered by the Sponsor as meeting exclusion criterion #14. 

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5.4 
Screen Failures  
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention. Screening information is recorded in 
the source documents. 
Individuals who do not meet the criteria for participation in this study (screen failure) cannot be 
rescreened. 
5.5 
Criteria for Temporarily Delaying Enrollment, Randomization, 
Administration of Study Intervention, or Blood Draws  
Not applicable. 
6 
Study Interventions and Concomitant Therapy  
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, 
or medical device(s) intended to be administered to a study participant according to the study 
protocol. 
Note: Vaccines or products administered outside of study protocol are not considered as study 
interventions and are reported in the CRF as reportable medications (see Section 6.8). Study 
procedures (eg, blood sampling) are also not considered as study interventions. 
6.1 
Study Interventions Administered  
Study interventions are described in Table 6.1. 
Table 6.1: Identity of study interventions  
Intervention Name 
Fluzone High-Dose Quadrivalent 
vaccine, 2021-2022 formulation 
Moderna COVID-19 Vaccine 
(mRNA-1273 vaccine) 
Use 
Experimental conditions or Other (as 
indicated in the prescribing material) 
Experimental conditions or Other (as 
indicated in the prescribing material) 
Type  
Vaccine 
Vaccine 
IMP and NIMP 
IMP 
IMP 
Dose Formulation 
Sterile suspension for injection in a 
pre-filled syringe 
Sterile suspension (white to off-
white) in multidose vial 
Unit Dose Strengths 
60 mcg of HA of each of the 
following strains per dose: 
• 
A/Victoria/2570/2019 IVR-215 
(H1N1) 
Each dose will contain 100 mcg of 
mRNA (formulated in SM-102 lipid 
nanoparticles) 

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• 
A/Tasmania/503/2020 IVR-221 
(an A/Cambodia/e0826360/2020-
like virus) (H3N2) 
• 
B/Phuket/3073/2013 (B 
Yamagata lineage) 
• 
B/Washington/02/2019 (B 
Victoria lineage) 
Excipients/Diluent 
Octylphenol ethoxylate (Triton X-
100), sodium phosphate-buffered 
isotonic sodium chloride solution 
Lipid SM-102 
Cholesterol 
1,2-distearoyl-sn-glycero-3-
phosphocholine (DSPC) 
1,2-Dimyristoyl-rac-glycero-3-
methoxypolyethylene glycol-2000 
(PEG2000 DMG) 
Tromethamol 
Tromethamol hydrochloride 
Acetic acid 
Sodium acetate trihydrate 
Sucrose 
Water for injections 
Dosage Level 
0.7 mL per dose 
0.5 mL per dose 
Number of 
Doses/Dosing 
Interval 
One injection at V1 (D01) alone or 
co-administered with Moderna 
COVID-19 Vaccine 
One injection at V1 (D01) alone or 
co-administered with Fluzone High-
Dose Quadrivalent vaccine 
Route of 
Administration 
IM injection 
IM injection 
Site of 
Administration 
Deltoid muscle in the upper arm  
Deltoid muscle in the upper arm  
Injection Site Side 
for Concomitant 
Administration 
Injection sites should be on opposite sides for participants enrolled in Group 1 
Sourcing 
Provided by the Sponsor 
Provided by the US Government 
Packaging and 
Labeling 
Fluzone High-Dose Quadrivalent vaccine and Moderna COVID-19 Vaccine 
will be supplied with their manufacturer’s commercial labeling and packaging. 
Batch Number 
TBD 
TBD 
Storage Conditions 
2 to 8°C 
2 to 8°C (up to 30 days) 
-25 to -15°C (long term) 
Study arms and associated study intervention are summarized in Table 6.2. 

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Table 6.2: Arms and Associated Study Interventions  
Arm name 
Group 1 
Group 2 
Group 3 
Associated study 
interventions 
Concomitant administration 
of Fluzone High-Dose 
Quadrivalent vaccine and 
Moderna COVID-19 Vaccine 
Fluzone High-Dose 
Quadrivalent vaccine 
alone 
Moderna COVID-19 
Vaccine alone 
6.2 
Preparation/Handling/Storage/Accountability  
Detailed guidance and information are provided in the Operating Guidelines. 
1) The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
2) Only participants enrolled in the study may receive study intervention and only authorized 
site staff may supply or administer study intervention. All study intervention must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
3) The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
4) Further guidance and information for the final disposition of unused study interventions are 
provided in the Operating Guidelines. 
6.3 
Measures to Minimize Bias: Randomization and Blinding  
6.3.1 
Randomization and Allocation Procedures  
Participants will be randomized in a 1:1:1 ratio into Group 1, Group 2, and Group 3, using a 
permuted block method with stratification by site and by age group (< 75 years and ≥ 75 years). 
The full detailed procedures for randomization are described in the Operating Guidelines. 
Participant numbers will be 12 digits long, with a 3-digit country identifier, a 4-digit study center 
identifier, and a 5-digit participant identifier. The 5-digit participant identifier will correspond to 
the chronological order of enrollment in the center within each stratum. For example, 
Participant 8400001-00001 is the first participant enrolled in Center Number 1 (in the US) and 
Participant 8400002-00002 is the second participant enrolled in Center Number 2 (in the US), 
within the < 75 years stratum. 
Participant numbers should not be reassigned for any reason. The randomization codes will be 
kept securely in an internal system. 

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The Biostatistics platform of the Sponsor will provide randomization lists that will be printed as 
scratchable lists. These lists will mention the randomization order of the participant and the 
corresponding study group covered by a silver-colored patch. The Investigator will scratch off the 
list to know the study group. Once scratched, each randomization line will be dated and signed by 
the Investigator or the sub-investigator in charge of administering the study intervention(s). 
Each participant will be vaccinated with the study intervention(s) corresponding to the group 
mentioned on the randomization list. If the dose initially taken for the vaccination is broken or 
cannot be used, the Investigator will take another dose of the same study intervention 
6.3.2 
Blinding and Code-breaking Procedures  
Code-breaking procedures are not applicable for this open-label study. However, the laboratories 
conducting immunogenicity assays will be blinded to individual participant assignment or 
treatment. 
6.4 
Study Intervention Compliance  
The following measures will ensure that the study intervention is administered as planned (see 
Table 6.1), and that any non-compliance is documented so that it can be accounted for in the data 
analyses: 
• All study interventions will be administered by qualified and trained study personnel 
• The person in charge of study intervention management at the site will maintain 
accountability records of study intervention delivery to the study site, study intervention 
inventory at the site, dose(s) given to each participant, and unused or wasted doses 
6.5 
Dose Modification  
Not applicable. 
6.6 
Continued Access to Study Intervention After the End of the Study  
Not applicable. 
6.7 
Treatment of Overdose  
Since the study intervention is administered by a health care professional, it is unlikely that 
overdose by injection occurs. 
However, in the event of an overdose, the investigator should: 
1) Contact the RMO immediately. 
2) Evaluate the participant to determine, in consultation with the RMO, whether study 
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3) Closely monitor the participant for any AE/SAE. 
4) Document the quantity of the excess of the overdose in the source documents. 
6.8 
Concomitant Therapy  
Reportable medications include medications that may affect the interpretation of safety data (eg, an 
antipyretic or analgesic that could have reduced the intensity or frequency of an adverse event) or 
may interfere with the development or measurement of the immune response (eg, the use of 
immune-suppressors, immune-modulators, or some antibiotics that can affect certain bioassays). 
Some medications such as steroids can affect both the evaluation of the safety and the immune 
response to a vaccine. 
This may include medications of interest that were started prior to the day of vaccination, and 
even stopped prior to enrollment if there is a reasonable possibility that they may have an impact 
on safety and / or immune assessment during study participation. 
The following reportable medications are defined: 
• medications impacting or that may have an impact on the evaluation of the safety (eg, 
antipyretics, analgesics, and non-steroidal anti-inflammatory drugs [NSAIDs], systemic 
steroids/corticosteroids) 
Note: Topical analgesics should NOT be applied at the injection site of study intervention; 
however, if they are applied inadvertently, they should be recorded. 
• medications impacting or that may have an impact on the immune response (eg, other 
vaccines, blood products, antibiotic classes that may interfere with bioassays used by 
Sanofi Pasteur laboratory or other testing laboratories, systemic steroids/corticosteroids, 
immune-suppressors, immune-modulators with immunosuppressive properties, anti-
proliferative drugs such as DNA synthesis inhibitors) 
• medications impacting or that may have an impact on both the safety and the immune 
response (eg, systemic steroids/corticosteroids) 
Reportable medications will be collected in the CRF until the end of the solicited and unsolicited 
follow-up period.  
Dosage and administration route, homeopathic medication, topical and inhaled steroids, as well as 
topical, ophthalmic, and ear treatments will not be recorded (except topical analgesics applied at the 
injection site of study intervention). 
Medications given in response to an AE will be captured in the “Action Taken” section of the AE 
CRF only. No details will be recorded in the concomitant medication Form of the CRF unless the 
medication(s) received belongs to one of the pre-listed categories. Medications will be coded.  
6.8.1 
Rescue Medicine  
Appropriate medical equipment and emergency medications, including epinephrine (1:1000), 
must be available at the study site in the event of an anaphylactic, vasovagal, or other immediate 
allergic reaction. 

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7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
7.1 
Discontinuation of Study Intervention  
Not applicable as there is only one vaccination visit. 
7.2 
Participant Discontinuation/Withdrawal from the Study  
• 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, or 
compliance reasons. This is expected to be uncommon. 
• 
The reason for withdrawal should be clearly documented in the source documents and in the 
CRF: Adverse Event, Lost to Follow-up, Protocol Deviation, or Withdrawal by Participant. 
• 
The participant will be permanently discontinued from the study at that time. 
• 
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• 
If a participant withdraws consent, he/she may request destruction of any biological samples 
taken (unless local law requires not to destroy them), and the investigator must document this 
in the site study records. 
• 
Withdrawn participants will not be replaced. 
Follow-up of Discontinuations 
For participants who have prematurely terminated the study, the site should attempt to contact 
them and complete all scheduled safety follow-ups, except if they specified that they do not want 
to be contacted again and it is documented in the source document. 
For participants where the reason for early termination is lost to follow-up, the site will not 
attempt to obtain further safety information. See Section 7.3 for definition of “lost to follow-up”. 
7.3 
Lost to Follow-up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the site for a required study 
visit or cannot be contacted as planned in the SoA: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 

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• 
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered lost to 
follow-up. 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 10.1. 
8 
Study Assessments and Procedures  
• 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Blood samples will be collected as described in the SoA table (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 40 mL, see Table 8.1. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
Table 8.1: Blood sampling volume (mL) per visit  
Visit Number 
(V) 
V01 
V02 
Trial Timelines (Days) 
D01 
D22 
Time Windows (Days) 
 
[+3 days] 
 
Vaccination 
Vaccination 
X 
 
 
Immunogenicity assessments related to Fluzone High-Dose 
Quadrivalent vaccine and Moderna COVID-19 Vaccine 

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exhibits complete inhibition of hemagglutination, the serum Ab titer will be reported as ≥ 10240 
(1/dil). 
8.1.2.2 
Immunogenicity Assessments Related to Moderna COVID-19 Vaccine 
Administration  
Human SARS-CoV-2 pre-Spike IgG ELISA 
The human SARS-CoV-2 Pre-Spike IgG ELISA is an indirect ELISA which is based on the 
antibody/antigen interactions. This ELISA allows for the detection of SARS-CoV-2 Pre-Spike 
specific IgG antibodies in human serum samples and will be performed on all participants from the 
3 study intervention groups. 
Purified SARS-CoV-2 Pre-Spike Antigen is adsorbed to the wells of a microplate. Diluted serum 
samples (test samples, standard, and quality controls) are added in the wells. Anti-SARS-CoV-2 
Pre-Spike antibodies, if present in the serum samples, bind to the immobilized SARS-CoV-2 Pre-
Spike antigen. Unbound sample is then washed from the wells, and enzyme-conjugated anti-human 
IgG is added. The anti-human IgG enzyme conjugate binds to the antigen-antibody complex. Excess 
conjugate is washed away, and a specific colorimetric substrate is added. Bound enzyme catalyzes 
a hydrolytic reaction, which causes color development. After the established time period, the 
reaction is stopped. The intensity of the generated color is proportional to the amount of anti-SARS-
CoV-2 Pre-Spike antibodies bound to the wells. The results are read on a spectrophotometer (ELISA 
plate reader). A reference standard on each tested plate is used to quantify antibodies against SARS-
CoV-2 Pre-Spike in the sample according to the unit assigned by the standard (ELU/mL). At the 
time of the statistical analysis of the results, the following formula will be used for converting the 
concentration units from ELU/mL to BAU/mL: 
Result (BAU/mL) = Result (ELU/mL)/7.9815 
8.2 
Safety Assessments  
This section presents safety assessments other than adverse events which are presented in 
Section 8.3. 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1 
Medical History  
Prior to enrollment, participants will be assessed for pre-existing conditions and illnesses, both 
past and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the participant is or has been followed by a physician or conditions/illnesses that could 
resume during the course of the study or lead to an SAE or to a repetitive outpatient care will be 
collected in the CRF.  
Prior history of SARS-CoV-2 infection will be collected. 
Collected information will not be coded.  

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8.2.2 
Physical Examinations  
At Visit 1, the Investigator or a designee will perform a targeted physical examination. 
Information will be recorded in the source document. 
8.2.3 
Vital Signs  
Oral pre-vaccination temperature will be systematically collected by the investigator on the source 
document. Tympanic, skin, and temporal artery thermometers must not be used. 
8.3 
Adverse Events (AEs), Serious Adverse Events, and Other Safety Reporting  
The definitions of an AE, SAE, and the different categories of AEs can be found in 
Appendix 10.2. 
AEs will be reported by the participants to the investigator, then by the investigator to the 
Sponsor. 
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 for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the procedures 
for completing and transmitting SAE reports are provided in Appendix 10.2. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information  
Immediate Post-vaccination Observation Period 
Participants will be kept under observation for 30 minutes after vaccination to ensure their safety. 
The post-vaccination observation should be documented in the source document. 
Reactogenicity 
Solicited injection site reactions will be collected from the day of vaccination (D01) until 7 days 
after vaccination (D08). 
Solicited systemic reactions will be collected from the day of vaccination (D01) until 7 days after 
vaccination (D08). 
The solicited injection site reactions and systemic reactions that are pre-listed in the diary cards 
and CRF, together with the intensity scales, are presented in Appendix 10.2.5.1.1. 
Unsolicited Non-serious Adverse Events 
Unsolicited non-serious adverse events will be collected from the day of vaccination (D01) until 
21 days after vaccination (D22). 

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The intensity grading scale for unsolicited non-serious adverse events is presented in 
Appendix 10.2.5.1.2. 
Medically Attended Adverse Events (MAAEs) 
MAAEs will be collected from D01 to D181. 
Adverse Events of Special Interest (AESIs) 
AESIs will be collected from D01 to D181. 
See Section 8.3.6 for the list of AESIs. 
SAEs 
Information on SAEs will be collected and assessed throughout the study, from the time of 
vaccination (D01) until 6 months after vaccination (D181). However, before the first study 
intervention administration, only SAEs related to study procedures are to be collected in the case 
report form (CRF). 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 10.2. The investigator will 
submit any updated SAE data to the Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must promptly 
notify the Sponsor. 
8.3.2 
Method of Detecting AEs and SAEs  
Individual diary cards, specifically designed for this study by the Sponsor and provided to the 
study sites, will be given to study participants for the recording of daily safety information. These 
diary cards will include pre-listed terms and intensity scales as well as areas for free text to 
capture additional safety information or other relevant details. Participants will also be provided 
with rulers for measuring the size of injection site reactions, and with standard digital 
thermometers for measuring daily temperatures. To ensure consistency of reporting, the study 
sites will instruct participants on how to correctly use these tools. 
At specified intervals, the Investigator or a designee will interview the participants to collect the 
information recorded in the diary card, and will attempt to clarify anything that is incomplete or 
unclear. All clinical study information gathered by the study site will be reported electronically by 
the Investigator or designee using a web-based CRF. Any information that was not documented in 
the diary card will first be captured in the source document and then reported electronically. 
The 6-month follow-up will be done by interviewing participants over the telephone to capture 
SAEs, AESIs, and MAAEs if applicable. 

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Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the Investigator is required to proactively follow each participant 
at subsequent visits/contacts, unless a participant refuses further contact. All AEs that are 
considered by the Investigator as serious, or related to the study intervention administered, or that 
led to study or vaccination discontinuation, or AESIs (as defined in Section 8.3.6), will be 
followed during the conduct of the study until resolution, stabilization, or the participant is lost to 
follow-up (as defined in Section 7.3). For related SAEs ongoing at last study visit, such follow-up 
may need to continue after the end of the study.  
Further information on follow-up procedures is provided in Appendix 10.2. 
8.3.4 
Regulatory Reporting Requirements for SAEs  
• 
Prompt notification by the investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
• 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics 
Committees (IEC), and investigators. 
• 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then 
file it and will notify the IRB/IEC, if appropriate according to local requirements. 
• 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary. 
8.3.5 
Pregnancy  
Not applicable as the study does not include women of childbearing potential. 
8.3.6 
Adverse Events of Special Interest  
AESI will be captured as SAEs and will include: 
Fluzone High-Dose Quadrivalent vaccine-related AESIs 
• Guillain-Barré Syndrome 
• Encephalitis/myelitis (including transverse myelitis) 
• Neuritis (including Bell’s palsy, optic neuritis, and brachial neuritis) 

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• Thrombocytopenia 
• Vasculitis 
• Convulsions 
• Anaphylaxis or other hypersensitivity/allergic reactions 
Moderna COVID-19 Vaccine-related AESIs 
Medical Concept  
Additional Notes  
Anosmia, Ageusia 
• 
New onset COVID associated or idiopathic events without other etiology 
excluding congenital etiologies or trauma  
Subacute thyroiditis 
• 
Including but not limited to events of: atrophic thyroiditis, autoimmune 
thyroiditis, immune-mediated thyroiditis, silent thyroiditis, thyrotoxicosis 
and thyroiditis  
Acute pancreatitis 
• 
Including but not limited to events of: autoimmune pancreatitis, immune-
mediated pancreatitis, ischemic pancreatitis, edematous pancreatitis, 
pancreatitis, acute pancreatitis, hemorrhagic pancreatitis, necrotizing 
pancreatitis, viral pancreatitis, and subacute pancreatitis  
• 
Excluding known etiologic causes of pancreatitis (alcohol, gallstones, 
trauma, recent invasive procedures)  
Appendicitis 
• 
Include any event of appendicitis 
Rhabdomyolysis 
• 
New onset rhabdomyolysis without known etiology such as excessive 
exercise or trauma  
Acute respiratory 
distress syndrome 
(ARDS) 
• 
Including but not limited to new events of ARDS and respiratory failure. 
Coagulation disorders 
• 
Including but not limited to thromboembolic and bleeding disorders, 
disseminated intravascular coagulation, pulmonary embolism, deep vein 
thrombosis   
Acute cardiovascular 
injury 
• 
Including but not limited to myocarditis, pericarditis, myopericarditis, 
microangiopathy, coronary artery disease, arrhythmia, stress 
cardiomyopathy, heart failure, or acute myocardial infarction  
Acute kidney injury 
• 
Include events with idiopathic or autoimmune etiologies  
• 
Exclude events with clear alternate etiology (trauma, infection, tumor, or 
iatrogenic causes such as medications or radiocontrast etc)  
• 
Include all cases that meet the following criteria   
o Increase in serum creatinine by ≥ 0.3 mg/dl (≥26.5 µmol/l) within 48 
hours;   
o OR Increase in serum creatinine to ≥ 1.5 times baseline, known or 
presumed to have occurred within prior 7 days   
o OR Urine volume ≤0.5 ml/ kg/ hour for 6 hours  

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Medical Concept  
Additional Notes  
Acute liver injury 
• 
Include events with idiopathic or autoimmune etiologies  
• 
Exclude events with clear alternate etiology (trauma, infection, tumor, 
etc)  
• 
Include all cases that meet the following criteria   
o 3-fold elevation above the upper normal limit for ALT or AST   
o OR > 2-fold elevation above the upper normal limit for total serum 
bilirubin or GGT or ALP  
Dermatologic findings 
• 
Chilblain-like lesions 
• 
Single organ cutaneous vasculitis 
• 
Erythema multiforme 
• 
Bullous rashes 
• 
Severe cutaneous adverse reactions including but not limited to: Stevens-
Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug 
Reaction with Eosinophilia and Systemic Symptoms (DRESS) and fixed 
drug eruptions  
Multisystem 
inflammatory 
disorders 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
Thrombocytopenia 
• 
Platelet counts < 150 x10^9 
• 
Including but not limited to immune thrombocytopenia, platelet 
production decreased, thrombocytopenia, thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura, or HELLP syndrome 
Acute aseptic arthritis 
• 
New onset aseptic arthritis without clear alternate etiology (eg gout, 
osteoarthritis, and trauma) 
New onset of or 
worsening of neurologic 
disease 
• 
Including but not limited to: 
o Guillain-Barré Syndrome 
o Acute disseminated encephalomyelitis (ADEM) 
o Peripheral facial nerve palsy (Bell’s palsy) 
o Transverse myelitis 
o Encephalitis/Encephalomyelitis 
o Aseptic meningitis 
o Febrile seizures 
o Generalized seizures/convulsions 
o Stroke (Hemorrhagic and non-hemorrhagic) 
o Narcolepsy 
Anaphylaxis 
Other syndromes 
• 
Fibromyalgia 

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Medical Concept  
Additional Notes  
• 
Postural Orthostatic Tachycardia Syndrome 
• 
Chronic Fatigue Syndrome (Includes myalgic encephalomyelitis and 
Post Viral Fatigue syndrome) 
• 
Myasthenia gravis 
8.3.7 
Medically Attended Adverse Events  
MAAEs will be collected using the same process as other AEs. See Appendix 10.2.1 for definition 
of MAAEs. 
8.4 
Pharmacokinetics  
Pharmacokinetics parameters are not evaluated in this study. 
8.5 
Genetics  
Genetics are not evaluated in this study. 
8.6 
Biomarkers  
No other biomarkers than those described in the immunogenicity assessments section 
(Section 8.1.2) are evaluated in this study. However, other emerging biomarkers may be evaluated 
in this study which may be relevant for evaluating scientific aspects of COVID-19 illness, or 
SARS-CoV-2 infection, or for the evaluation of effect modification, correlates of risk/protection, 
or participants’ baseline characteristics. 
8.7 
Immunogenicity Assessments  
See Section 8.1.2. 
8.8 
Medical Resource Utilization and Health Economics  
Medical Resource Utilization and Health Economics parameters will not be evaluated in this 
study. 
8.9 
Leftover Biological Samples and Use of Data  
Any unused part of the biological samples collected for this study (ie, serum samples) are being 
retained in long-term storage to support answers to regulatory questions related to the product’s 
licensure and the potential revalidation of the study results. 

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In addition, participants will be asked to indicate in the ICF whether they will permit the future 
use by Sanofi Pasteur or one of its research partners, of any unused stored biological samples for 
other tests and the corresponding data, unless prohibited by local laws or IRBs/IECs (in such case, 
consent for future use of any unused biological samples will not be included in the site-specific 
ICF). If they refuse permission, the biological samples will not be used for any testing other than 
that directly related to this study. If they agree to this future use, they will not be paid for giving 
permission.  
Data and samples will be used in compliance with the information provided to participants in the 
ICF Part 2 (future research). The aim of any possible future research is unknown today, and may 
not be related to this particular study. It may be to improve the knowledge of vaccines and their 
mechanism of action, the knowledge of infectious diseases, or to improve existing tests or develop 
new tests to assess vaccines, or to help identify new vaccine targets or biomarkers that predict 
participant response to the vaccine. Such research may also include, but is not limited to, 
performing assessments on DNA, RNA, proteins or metabolites. If future research on genetic 
material is performed, a specific individual consent will be obtained. 
All study participant data and biological samples will be coded such that no direct identifiers will 
be linked to participants. Coded data and biological samples may be transferred to a Sponsor site 
(or a subcontractor site), which may be located outside of the country where the study is 
conducted. The Sponsor adopts safeguards for protecting participant confidentiality and personal 
data (see Section 10.1.4). 
The biological samples will be securely stored at the Sanofi Pasteur laboratory (GCI) or Contract 
Research Laboratory up to 25 years after the end of the study. Unused samples may also be sent to 
another long-term repository at the NIH, BARDA, as well as other US Government-designated 
laboratories. Any samples remaining at the end of retention period will be destroyed. If a 
participant requests destruction of his/her samples before the end of the retention period, the 
Investigator must notify the Sponsor (or its contract organization) in writing. In such case, 
samples will be destroyed and sample related coded data will be anonymized unless otherwise 
required by applicable laws. 
Study participant coded data will be stored for future research for up to 25 years after the end of 
the study. If data are still considered of important scientific value after this period, coded data 
already available will be anonymized unless otherwise required by applicable laws (the same will 
apply to the data of a study participant who has requested the destruction of his/her samples). 
Participant’s coded data sets provided to researchers for a specific research project will be 
available to the researchers for a maximum of 2 years after the end of their specific project (end of 
project is defined by publication of the results or finalization of the future research project report). 
Note: The other biological samples collected to qualify the participant for inclusion in the study or 
to monitor his/her health during the study are dedicated for immediate use. If any of these 
biological samples are not completely used up, they will be destroyed at the latest at the end of the 
study or after the time requested by local law. 

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9 
Statistical Considerations  
9.1 
Statistical Hypotheses  
No hypothesis testing will be performed in this study. 
9.2 
Sample Size Determination  
The study will enroll approximately 300 participants 65 years of age or older: approximately 100 
participants will be concomitantly administered of Fluzone High-Dose Quadrivalent vaccine and 
Moderna COVID-19 Vaccine (Group 1), approximately 100 participants will be administered 
Fluzone High-Dose Quadrivalent vaccine alone (Group 2), and approximately 100 participants 
will be administered Moderna COVID-19 Vaccine alone (Group 3). 
No study power calculation was conducted for this study. Assuming a drop-out rate of 5%, a total 
of 95 evaluable subjects per study group is anticipated. 
9.3 
Analysis Sets  
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis 
Set 
Description 
Randomized 
All participants that have a randomization number 
Safety Analysis Set (SafAS) 
Participants who have received the study vaccine(s). All participants 
will have their safety analyzed according to the vaccine they actually 
received and study intervention group. 
Safety data recorded for a vaccine received out of the protocol design 
will be excluded from the analysis (and listed separately). 
Immunogenicity analysis set 
(IAS) 
Subset of randomized participants who received at least 1 dose of study 
vaccine. 
Participants will be analyzed according to the vaccine they actually 
received and study intervention group. 
9.4 
Statistical Analyses  
The statistical analysis plan (SAP) will be finalized prior to database lock and it will include a 
more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 

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9.4.1 
General Considerations  
All statistical analyses will be performed under the responsibility of the Sponsor’s Biostatistics 
Platform using the SAS® software, Version 9.4 or above (SAS Institute, Cary, North Carolina, 
USA). 
For the derivation of immunogenicity endpoints, all values strictly under the lower limit of 
quantification (LLOQ) will be treated as LLOQ/2, and all values above or equal to the upper limit 
of quantification (ULOQ) will be treated as ULOQ. 
9.4.2 
Study Endpoints  
All analyses will be descriptive. No hypotheses are planned to be tested. 
For the main parameters, 95% CIs for the point estimates will be calculated using the normal 
approximation after log transformation for quantitative data (GMCs and GM of individual ratios) 
and exact binomial distribution (Clopper-Pearson method, quoted by Newcombe) for single 
proportions.  
For immunogenicity analyses the IAS will be used. Results will be presented by actual study 
group and vaccine received for each timepoint. For the analysis of SARS COV-2 immune 
response, the serological results will be received in ELU/mL but will be expressed in BAU/mL for 
the analysis. The following formula will be used for converting the concentration units from 
ELU/mL to BAU/mL: 
Result (BAU/mL) = Result (ELU/mL)/7.9815 
For safety analyses the SafAS will be used. Results will be presented by actual study group and 
vaccine received. 
9.4.3 
Other Analysis  
The ratios of post-vaccination GMTs between concomitant and single injections will be presented 
for the five antigens with 2-sided 95% CIs. 
Subgroup analyses will also be performed as complementary analyses; in particular, 
immunogenicity will be described according to serostatus at baseline, previous influenza 
vaccination, and age, as appropriate according to number of subjects in the respective subgroups.  
Other analyses will be described in the SAP. 
9.5 
Interim Analyses  
The statistical analysis will be performed in two or three steps, depending on the availability of 
immunogenicity data: the safety objectives up to D22 will be analyzed first and the 
immunogenicity objectives will be analyzed in a second step, after immunogenicity data have 
been released. No impact is expected on immunogenicity results as the conduct of 
immunogenicity assays will remain blinded. At last, the final analysis will be performed when 
safety data up to D181 is released. 
 

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10 Supporting Documentation and Operational Considerations  
10.1 Appendix: Regulatory, Ethical, and Study Oversight Considerations  
Note: The term “participant” is used throughout this protocol. However, the term “subject” will be 
used in the CRF in order to comply with the Clinical Data Interchange Standards Consortium 
(CDISC) requirements. Similarly, “legally acceptable representative” is used in the protocol 
whereas “guardian” is used in the CRF. 
10.1.1 Regulatory and Ethical Considerations  
• This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations (eg, data protection law as General Data Protection 
Regulation [GDPR]) 
• The protocol, informed consent form (ICF), product-related information (ie, US PI for Fluzone 
High-Dose Quadrivalent vaccine and the Investigator’s Brochure for Moderna COVID-19 
Vaccine), and other relevant documents (eg, advertisements) must be submitted to an IRB/IEC 
by the investigator or the Sponsor (according to local regulations) and reviewed and approved 
by the IRB/IEC before the study is initiated 
• Any amendments to the protocol will require IRB/IEC 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/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• 
Determining whether an incidental finding (as per Sanofi policy) should be returned to a 
participant and, if it meets the appropriate criteria, to ensure the finding is returned (an 
incidental finding is a previously undiagnosed medical condition that is discovered 
unintentionally and is unrelated to the aims of the study for which the tests are being 
performed). The following should be considered when determining the return of an 
incidental finding: 

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• The return of such information to the study participant (and/or his/her designated 
healthcare professional, if so designated by the participant) is consistent with all 
applicable national, state, or regional laws and regulations in the country where the 
study is being conducted, and 
• The finding reveals a substantial risk of a serious health condition or has 
reproductive importance, AND has analytical validity, AND has clinical validity.  
• The participant in a clinical study has the right to opt out of being notified by the 
Investigator of such incidental findings. In the event that the participant has opted out 
of being notified and the finding has consequences for other individuals, eg, the 
finding relates to a communicable disease, Investigators should seek independent 
ethical advice before determining next steps. 
• In case the participant has decided to opt out, the Investigator must record in the 
site medical files that she/he does not want to know about such findings. 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), European Medical Device Regulation 2017/745 for clinical device 
research (if applicable), and all other applicable local regulations 
As applicable, according to Directive 2001/20/EC, the Sponsor will be responsible for obtaining 
approval from the Competent Authorities of the EU Member States and/or Ethics Committees, as 
appropriate, for any amendments to the clinical trial that are deemed as “substantial” (ie, changes 
which are likely to have a significant impact on the safety or physical or mental integrity of the 
clinical trial participants or on the scientific value of the trial) prior to their implementation. 
10.1.2 Financial Disclosure  
Information related to financial disclosure is described in the Investigator’s contract. 
10.1.3 Informed Consent Process  
• The investigator or his/her representative will explain the nature of the study to the participant 
and answer all questions regarding the study. 
• Participants must be informed that their participation is voluntary. Participants will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 

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• The actual ICF used at each center may differ, depending on local regulations and IEC / IRB 
requirements. However, all versions must contain the standard information found in the 
sample ICF provided by the Sponsor. Any change to the content of the ICF must be approved 
by the Sponsor and the IEC / IRB prior to the form being used. 
• If new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study, this will be communicated to him / her in a timely manner. 
Such information will be provided via a revised ICF or an addendum to the original ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant. 
The ICF will contain a specific section that addresses the use of remaining mandatory samples for 
optional exploratory research, unless prohibited by local laws or IRBs/IECs. The investigator or 
designee will explain to each participant the objectives of the exploratory research. Participants 
will be told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period. 
Recruitment Procedures 
Before the start of the study, the Investigator or sub-investigator will contact an appropriate pool 
of potential participants and invite them to participate in the study. The site will ensure that any 
advertisements used to recruit participants (eg, letters, pamphlets, posters) are submitted to Sanofi 
Pasteur for review prior to submission to the IEC/IRB for approval. 
10.1.4 Data Protection  
All personal data collected and/or processed in relation to this study will be handled in compliance 
with all applicable Privacy & Data Protection laws and regulations, including the GDPR (General 
Data Protection Regulation). The study Sponsor is the Sanofi company responsible for ensuring 
compliance with this matter, when processing data from any individual who may be included in 
the Sanofi databases, including Investigators, nurses, experts, service providers, Ethics Committee 
members, etc.  
When archiving or processing personal data pertaining to the Investigator and/or to the 
participants, the Sponsor shall take all appropriate measures to safeguard and prevent access to 
this data by any unauthorized third party. 
Protection of participant data 
Data collected must be adequate, relevant and not excessive, in relation to the purposes for which 
they are collected. Each category of data must be properly justified and in line with the study 
objective. 
• Participants race and ethnicity will be collected in this study because these data are required 
by the FDA (27). 

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• Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor or its service providers will be identifiable only by 
the unique identifier; participant names or any information which would make the participant 
identifiable will not be transferred to the Sponsor. 
• The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with applicable data protection law. The level of disclosure must also 
be explained to the participant as described in the informed consent. 
• The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
• Participants must be informed that their study-related data will be used for the whole “drug 
development program”, ie, for this trial as well as for the following steps necessary for the 
development of the investigational product, including to support negotiations with payers and 
publication of results. 
Protection of data related to professionals involved in the study  
• Personal data (eg, contact details, affiliation(s) details, job title and related professional 
information, role in the study, professional resume, training records) are necessary to allow 
Sanofi to manage involvement in the study and/or the related contractual or pre-contractual 
relationship. They may be communicated to any company of the Sanofi group (“Sanofi”) or to 
Sanofi service providers, where needed. 
• Personal data can be processed for other studies and projects.  
• In case of refusal to the processing of personal data by or on behalf of Sanofi, it will be 
impossible to involve the professionals in any Sanofi study. In case the professionals have 
already been involved in a Sanofi study, they will not be able to object to the processing of 
their personal data as long as they are required to be processed by applicable regulations. The 
same rule applies in case the professionals are listed on a regulatory agencies disqualification 
list. 
• Personal data can be communicated to the following recipients:  
• Personnel within Sanofi or partners or service providers involved in the study  
• Judicial, administrative and regulatory authorities, in order to comply with legal or 
regulatory requirements and/or to respond to specific requests or orders in the 
framework of judicial or administrative procedures. Contact details and identity may 
also be published on public websites in the interest of scientific research transparency 
• Personal data may be transferred towards entities located outside the Economic European 
Area, in countries where the legislation does not necessarily offer the same level of data 
protection or in countries not recognized by the European Commission as offering an adequate 
level of protection. Those transfers are safeguarded by Sanofi in accordance with the 
requirement of European law including, notably:  
• The standard contractual clauses of the European Commission for transfers towards 
our partners and service providers, 

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• Sanofi’s Binding Corporate Rules for intra-group transfers.  
• Professionals have the possibility to lodge a complaint with Sanofi leading Supervisory 
Authority, the “Commission Nationale de l’Informatique et des Libertés” (CNIL) or with any 
competent local regulatory authority. 
• Personal data of professionals will be retained by Sanofi for up to thirty (30) years, unless 
further retention is required by applicable regulations. 
• In order to facilitate the maintenance of Investigators personal data, especially if they 
contribute to studies sponsored by several pharmaceuticals companies, Sanofi participates in 
the Shared Investigator Platform (SIP) and in the Transcelerate Investigator Registry (IR) 
project (https://transceleratebiopharmainc.com/initiatives/investigator-registry/). Therefore, 
personal data will be securely shared by Sanofi with other pharmaceutical company members 
of the Transcelerate project. This sharing allows Investigators to keep their data up-to-date 
once for all across pharmaceutical companies participating in the project, with the right to 
object to the transfer of the data to the Transcelerate project.  
• Professionals have the right to object to the processing, to request for access to and the 
rectification of their personal data, as well as their erasure (where applicable) by contacting 
the Sanofi Data Protection Officer: Sanofi DPO - 54 rue La Boétie - 75008 PARIS - France (to 
contact Sanofi by email, visit https://www.sanofi.com/en/our-responsibility/sanofi-global-
privacy-policy/contact). 
10.1.5 Dissemination of Clinical Study Data  
Study participants 
Sanofi shares information about clinical trials and results on publicly accessible websites, based 
on company commitments, international and local legal and regulatory requirements, and other 
clinical trial disclosure commitments established by pharmaceutical industry associations.  These 
websites include clinicaltrials.gov, EU clinicaltrialregister (eu.ctr), and sanofi.com, as well as 
some national registries. 
In addition, results from clinical trials in patients are required to be submitted to peer-reviewed 
journals following internal company review for accuracy, fair balance, and intellectual property. 
For those journals that request sharing of the analyzable data sets that are reported in the 
publication, interested researchers are directed to submit their request to 
clinicalstudydatarequest.com. 
Individual participant data and supporting clinical documents are available for request at 
clinicalstudydatarequest.com. While making information available we continue to protect the 
privacy of participants in our clinical trials. Details on data sharing criteria and process for 
requesting access can be found at this web address: clinicalstudydatarequest.com. 
Professionals involved in the study or in the drug development program 
Sanofi may publicly disclose, and communicate to relevant authorities/institutions, the funding, 
including payments and transfers of value, direct or indirect, made to healthcare organizations and 
professionals and/or any direct or indirect advantages and/or any related information or document 

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if required by applicable law, by regulation or by a code of conduct such as the “EFPIA Code on 
Disclosure of Transfers of Value from Pharmaceutical Companies to Healthcare Professionals and 
Healthcare Organisations”. 
10.1.6 Data Quality Assurance  
• All participant data relating to the study will be recorded on 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 Instructions.. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring) are provided in the Monitoring 
Plan. 
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
• Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 25 years after the signature of the final study report 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. 
10.1.7 Source Documents  
“Source data” are the data contained in source documents. Source documents are original 
documents or certified copies, and include, but are not limited to, diary cards, medical and 
hospital records, screening logs, informed consent / assent forms, telephone contact logs, and 
worksheets. 
• 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’s site. 
• Data entered in the CRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 

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• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Detailed guidance and information are provided in the Operating Guidelines. 
10.1.8 Study and Site Start and Closure  
Details on which clinical supplies are provided by the Sponsor or the site are described in the 
Operating Guidelines. 
The study start date is considered the date of the first visit planned in the SoA of the first 
participant. 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been either destroyed or returned to the Sponsor, all samples are shipped to the appropriate 
laboratories, the center study-site has all the documents necessary for archiving and a study-site 
closure visit has been performed along with a Site Close Out Form submitted to the IRB, as 
required. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are not 
limited to: 
For study termination: 
• Discontinuation of further study intervention development 
• Information on the study intervention leads to doubt as to the benefit/risk ratio 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants by 
the investigator 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 

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and onset) pre-listed in the protocol and CRF. It is considered by default as being related to the 
IMP administered at that site. 
Note: « Administration site reaction » term is only to be used for vaccines that are not intended 
to be administered by injection. 
Systemic AR: 
Systemic ARs are all ARs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 
manifestations that are not associated with the injection or administration site (eg, erythema that 
is localized but that is not occurring at the injection site).  
Solicited systemic reactions are systemic AEs observed and reported under the conditions 
(nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions occurring 
during the specified collection period are always considered related to the IMP even if there is 
evidence of alternative etiology. 
 
Unsolicited AE/AR 
An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, 
ie, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination. For example, 
varicella or a solicited term such as headache starting after the solicited observation period (eg, 
headache starting on Day 10 post-vaccination in the case where headache occurring between the 
day of vaccination and the next 7 days is pre-listed in the protocol and CRF as a solicited 
reaction). 
An unsolicited AR is an unsolicited AE that is considered related to an IMP.  
Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. 
All unsolicited AEs occurring at and around the IMP injection/administration site are to be 
considered by default as related to the IMP administered at that site and are therefore referred as 
unsolicited injection/administration site ARs. 
All unsolicited AEs which are not at and around the IMP injection/administration site, are 
referred as systemic unsolicited AE. For each unsolicited systemic AE, the investigator assesses 
the relationship to the IMP. Systemic AEs assessed as related to IMP are referred as systemic 
ARs. 
Adverse Event of Special Interest (AESI): 
An adverse event of special interest (serious or non-serious) is one of scientific and medical 
concern specific to the Sponsor’s study intervention or program, for which ongoing monitoring 
and rapid communication by the investigator to the Sponsor can be appropriate. Such an event 
might warrant further investigation in order to characterize and understand it. Depending on the 
nature of the event, rapid communication by the study Sponsor to other parties (eg, regulators) 
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therefore are referred to as reactions and do not require the Investigator’s opinion on 
relatedness. 
• Causal relationship of unsolicited systemic AEs and SAEs will be recorded as follows: 
• 
For non-serious unsolicited systemic AEs (except for non-serious AESIs), relationship 
to study intervention will usually be assessed by the Investigator only.   
• 
For SAEs and non-serious AESIs, relationship to study intervention will be assessed 
by both the Investigator and the Sponsor (except for injection site reactions which will 
be related by default). Sponsor assessment is entered in the GPV database only.   
• 
For SAEs only, the causal relationship to study procedures (related/not related to study 
procedures) will be assessed by both the Investigator and the Sponsor. Sponsor 
assessment is entered in the GPV database only. 
• The Investigator will assess the causal relationship between each unsolicited systemic AE 
and the study intervention administered as either not related or related, based on the 
following definitions: 
• 
Not related – The AE is clearly / most probably caused by other etiologies such as 
participants’ underlying condition, therapeutic intervention, or concomitant therapy; or 
the delay between vaccination and the onset of the AE is incompatible with a causal 
relationship; or the AE started before the vaccination (screening phase, if applicable) 
• 
Related – There is a “reasonable possibility” that the AE was caused by the study 
intervention administered, meaning that there are facts (evidence) or arguments to 
suggest a causal relationship 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated. 
• The investigator will also consult the IB and/or Product Information, for marketed products, 
in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causal relationship. 
• There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that 
the investigator always makes an assessment of causal relationship for every event before 
the initial transmission of the SAE data to the Sponsor. 
• The investigator may change his/her opinion of causal relationship in light of follow-up 
information and send an SAE follow-up report with the updated causal relationship 
assessment. 
• The causal relationship assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 

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Table 10.1: Solicited injection site reactions: terminology, definitions, and intensity scales – Adults  
CRF term 
(MedDRA 
lowest level 
term [LLT]) 
Injection site pain 
Axillary swelling 
Axillary tenderness 
Injection site 
erythema 
Injection site 
swelling 
Injection site 
induration 
Injection site 
bruising 
Diary card 
term 
Pain 
Underarm swelling 
Underarm pain 
Redness 
Swelling 
Hardening 
Bruising 
Definition 
Pain either present 
spontaneously or when 
the injection site is 
touched or injected 
limb is mobilized 
Axillary (underarm) 
swelling ipsilateral to 
the side of injection 
 
Axillary (underarm) 
tenderness ipsilateral to 
the side of injection 
 
Presence of a 
redness including 
the approximate 
point of needle 
entry 
Swelling at or 
near the injection 
site 
Swelling or 
edema is caused 
by a fluid 
infiltration in 
tissue or cavity 
and, depending on 
the space 
available for the 
fluid to disperse, 
swelling may be 
either soft 
(typically) or firm 
(less typical) to 
touch and thus 
can be best 
described by 
looking at the size 
of the swelling 
Hardening at or 
near the injection 
site. Hardening is 
caused by a slow 
diffusion of the 
product in the 
tissue leading to a 
thick or hard area 
to touch at or near 
the injection site 
and thus can be 
best described by 
looking at the size 
of the hardening. 
Bruising is the 
result of the 
diffusion of blood 
in the skin from 
ruptured blood 
vessels that forms 
a purple or black 
and blue spot on 
the skin. It can be 
best described by 
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Intensity 
scale* 
 
CRF: 
Grade 1: A type of adverse event that is usually transient and may require 
only minimal treatment or therapeutic intervention. The event does not 
generally interfere with usual activities of daily living. 
Grade 2: A type of adverse event that is usually alleviated with additional 
therapeutic intervention. The event interferes with usual activities of daily 
living, causing discomfort but poses no significant or permanent risk of harm 
to the research participant. 
Grade 3: A type of adverse event that interrupts usual activities of daily 
living, or significantly affects clinical status, or may require intensive 
therapeutic intervention. 
Diary card: 
Grade 1: No interference with activity 
Grade 2: Some interference with activity 
Grade 3: Significant; prevents daily activity 
Grade 1: ≥ 25 to 
≤ 50 mm 
Grade 2: ≥ 51 to 
≤ 100 mm 
Grade 3: 
> 100 mm 
Grade 1: ≥ 25 to 
≤ 50 mm 
Grade 2: ≥ 51 to 
≤ 100 mm 
Grade 3: 
> 100 mm 
Grade 1: ≥ 25 to 
≤ 50 mm 
Grade 2: ≥ 51 to 
≤ 100 mm 
Grade 3: > 100 
mm 
Grade 1: ≥ 25 to 
≤ 50 mm 
Grade 2: ≥ 51 to 
≤ 100 mm 
Grade 3: > 100 
mm 
MedDRA: Medical Dictionary for Regulatory Activities 
*    For pain, the scale will be provided in the CRF and the intensity will be transcribed from the diary card. For other injection site reactions (erythema and swelling), the classification as 
Grades 1, 2, or 3 will be applied at the time of statistical analysis; the scale is provided for information purposes only. The actual size of the reaction will be reported in the CRF. 
 
 

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Table 10.2: Solicited systemic reactions: terminology, definitions, and intensity scales – Adults  
CRF term 
(MedDRA 
lowest 
level term 
[LLT]) 
Fever 
Headache 
Malaise 
Myalgia 
Arthralgia 
Shivering 
Fatigue 
Nausea 
Vomiting 
Diary 
card term 
Temperature 
Headache 
Feeling unwell 
Muscle aches and pains 
Joint pain 
Chills 
Tiredness 
Feeling sick 
Vomiting 
Definition 
Elevation of 
temperature to 
≥°38.0°C 
(≥ 100.4°F) 
Pain or 
discomfort 
in the head 
or scalp. 
Does not 
include 
migraine. 
General ill feeling. 
Malaise is a generalized 
feeling of discomfort, 
illness, or lack of well-
being that can be 
associated with a disease 
state. It can be 
accompanied by a 
sensation of exhaustion 
or inadequate energy to 
accomplish usual 
activities. 
Muscle aches and pains 
are common and can 
involve more than one 
muscle at the same time. 
Muscle pain can also 
involve the soft tissues 
that surround muscles. 
These structures, which 
are often referred to as 
connective tissues, 
include ligaments, 
tendons, and fascia 
(thick bands of tendons). 
Does not apply to 
muscle pain at the 
injection site which 
should be reported as 
injection site pain. 
Pain in a 
joint or 
joints  
Cold feeling 
Overall 
feeling of 
tiredness or 
lack of 
energy 
Feeling of 
sickness 
with 
inclination 
to vomit 
Forceful 
expulsion of 
the contents 
of the 
stomach via 
the mouth or 
sometimes 
the nose; 
emesis. 
Vomiting 
does not 
include 
spitting up. 
Intensity 
scale* 
Grade 1: 
≥ 38.0°C to 
≤ 38.4°C, 
CRF: 
Grade 1: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not 
generally interfere with usual activities of daily living. 

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or ≥ 100.4°F to 
≤ 101.1°F 
 
Grade 2: 
≥ 38.5°C to 
≤ 38.9°C, 
or ≥ 101.2°F to 
≤ 102.0°F 
Grade 2: A type of adverse event that is usually alleviated with additional therapeutic intervention. The event interferes with usual activities of 
daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. 
 
Grade 3: 
≥ 39.0°C 
or ≥ 102.1°F 
Grade 3: A type of adverse event that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive 
therapeutic intervention. 
Diary card: 
Grade 1: No interference with activity 
Grade 2: Some interference with activity 
Grade 3: Significant; prevents daily activity 
MedDRA: Medical Dictionary for Regulatory Activities 
*    For all reactions (except fever), the scale will be provided in the CRF and the intensity will be transcribed from the diary card. For fever, the body temperature will be recorded, 
and the classification as Grade 1, 2, or 3 will be assigned at the time of the statistical analysis based on the unit used to measure the temperature and the intensity scale. 
 

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Important notes for the accurate assessment of temperature: 
Participants are to measure body temperature once per day, preferably always at the same time. 
The optimal time for measurement is the evening, when body temperature is the highest. 
Temperature is also to be measured at the time of any apparent fever. The observed daily 
temperature and the route of measurement are to be recorded in the diary card, and the highest 
temperature will be recorded by the site in the CRF. The preferred route for this study is oral. 
10.2.5.1.2 Unsolicited AE Intensity Grading Scale  
For measurable unsolicited AEs that are part of the list of solicited reactions, the corresponding 
scale for solicited reactions will be used (see Section 10.2.5.1.1). 
All other unsolicited AEs will be classified according to the following intensity scale: 
• Grade 1 
• 
CRF: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
• 
Diary card: No interference with activity. 
• Grade 2 
• 
CRF: A type of adverse event that is usually alleviated with additional therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort 
but poses no significant or permanent risk of harm to the research participant. 
• 
Diary card: Some interference with activity. 
• Grade 3 
• 
CRF: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. 
• 
Diary card: Significant; prevents daily activity. 
 
 

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10.3 Appendix: Risk-based Approach  
ICH E6-R2 guideline for GCP is introducing the « risk-based approach » concept which permits 
to focus efforts on what is critical for a study and most specifically on Critical Data and Critical 
Processes. Critical data and processes are defined for the study with associated risks in the Study 
Risk Management Plan. 

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10.4 Appendix: Abbreviations  
ACIP   
Advisory Committee on Immunization Practices 
AE 
 
Adverse Events 
AESI  
Adverse events of special interest 
AR 
 
Adverse reactions 
BL 
 
blood sample 
CRF  
Case report form 
DMC  
Data Monitoring Committee 
FAS 
 
Full analysis set 
GBS  
Guillain-Barré syndrome 
GCI 
 
Global Clinical Immunology 
GCP  
Good Clinical Practice 
GM 
 
geometric mean 
GMT  
geometric mean of titers 
GPV  
Global Pharmacovigilance 
HA 
 
Hemagglutinin 
HAI 
 
Hemagglutinin inhibition 
HRT  
Hormonal replacement therapy 
IB 
 
Investigator’s Brochure 
ICF 
 
informed consent form 
ICH 
 
International Council for Harmonisation 
IDMC  
Independent Data Monitoring Committee 
IEC 
 
Independent Ethics Committees 
IM 
 
intramuscular 
IMP 
 
Investigational Medicinal Product 
IRB 
 
Institutional Review Boards 
LLOQ  
lower limit of quantification 
LNP   
lipid nanoparticle 
MA 
 
memory aid 
MAAE 
medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities 

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NIAID  
National Institute of Allergy and Infectious Diseases  
NIH   
National Institutes of Health 
NIMP  
Non- Investigational Medicinal Product 
PPAS  
Per-protocol analysis set 
PV 
 
Pharmacovigilance 
PT 
 
Preferred Term 
RMO  
Responsible Medical Officer 
SAE  
Serious adverse events 
SafAS  
Safety Analysis Set 
SAP 
 
Statistical analysis plan 
SoA 
 
Schedule of Activities 
SOC  
System Organ Class 
SUSAR 
suspected unexpected serious adverse reactions 
TBD  
to be determined 
ULOQ  
upper limit of quantification 
WHO  
World Health Organization 
VAC  
vaccination 

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10.5 Appendix: Protocol Amendment/Update History  
The Protocol Amendment rationale for the current change in versions (from version 3.0 to version 
4.0) is located directly before the Table of Contents. 
Protocol version 2.0, dated 22 June 2021 
Following the Institutional Review Board review, Protocol version 1.0 dated 10 June 2021 was 
updated to change the dosage of the Moderna COVID-19 Vaccine from 50 mcg to 100 mcg.  
Protocol version 3.0 (Amendment 1), dated 01 July 2021 
The main reason for updating protocol version 2.0 to protocol version 3.0 (Amendment 1) was to 
add the following items following the review of the Center for Biologics Evaluation and Research 
(United States Food and Drug Administration): 
• Indicate the designated laboratory that will be performing the immunological assays. 
• Offer participants enrolled in Group 3 (Moderna COVID-19 Vaccine alone) vaccination 
with Fluzone High-Dose Quadrivalent vaccine at the conclusion of their study 
participation (Visit 02) as part of routine medical care. 
 
 

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Woo EJ. Allergic reactions after egg-free recombinant influenza vaccine: reports to the US 
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