A Phase III, Randomized, Open-label, Controlled, Multicenter Study to Evaluate the Immune Response and Safety of Both Herpes Zoster Subunit Vaccine in Healthy Adults Aged 50 Years and Older AND the Influenza Virus Vaccine in Healthy Adults Aged 18 Years and Older When Administered Sequentially or Coadministered With mRNA-1273 Booster Vaccination
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
Primary study 
intervention and number 
GSK’s lyophilized formulation of the Herpes Zoster 
subunit vaccine (GSK1437173A)  
GSK’s FLU D-QIV (Quadrivalent Inactivated Split 
Virion Influenza Vaccine) (GSK2321138A) 
Other study interventions 
COVID-19 mRNA-1273 vaccine 
eTrack study number and 
abbreviated title 
217670 (ZOSTER-091) 
Date of protocol 
Final: 3 August 2021 
Date of protocol 
amendment 
Amendment 1 Final: 21 September 2021 
Title 
A Phase III, randomized, open-label, controlled, 
multi-center study to evaluate the immune response 
and safety of both herpes zoster subunit vaccine in 
healthy adults aged 50 years and older AND the 
influenza virus vaccine in healthy adults aged 18 years 
and older when administered sequentially or 
co-administered with mRNA-1273 booster vaccination. 
Brief title 
A study on the immune response and safety of the 
shingles vaccine and the influenza vaccine when either 
is given to healthy adults at the same time or following 
a COVID-19 booster vaccine. 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.2 
©2021 GSK group of companies or its licensor. 
 

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Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number 
and abbreviated title 
217670 (ZOSTER-091) 
Date of protocol 
Final: 3 August 2021 
Date of protocol 
amendment 
Amendment 1 Final: 21 September 2021 
Title 
A Phase III, randomized, open-label, controlled, multi-center 
study to evaluate the immune response and safety of both 
herpes zoster subunit vaccine in healthy adults aged 50 years 
and older AND the influenza virus vaccine in healthy adults 
aged 18 years and older when administered sequentially or 
co-administered with mRNA-1273 booster vaccination. 
Sponsor signatory 
Agnes Mwakingwe-Omari, 
Clinical and Epidemiology Project Leader for ZOSTER, 
Clinical Research & Development - United States, 
GlaxoSmithKline Biologicals SA 
Signature 
 
 
 
Date 
 
 
 
Sponsor signatory 
Jerome Wilson, 
Clinical and Epidemiology Project Leader for Influenza, 
Clinical Research & Development - United States, 
GlaxoSmithKline Biologicals SA 
Signature 
 
 
 
Date 
 
Note: Not applicable if an alternative signature process (e.g., electronic signature or 
email approval) is used to get the sponsor approval.  

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Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• 
That I will comply with the terms of the site agreement. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

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eTrack study number and 
abbreviated title 
217670 (ZOSTER-091) 
Date of protocol 
Final: 3 August 2021 
Date of protocol 
amendment 
Amendment 1 Final: 21 September 2021 
Title 
A Phase III, randomized, open-label, controlled, 
multi-center study to evaluate the immune response 
and safety of both herpes zoster subunit vaccine in 
healthy adults aged 50 years and older AND the 
influenza virus vaccine in healthy adults aged 18 years 
and older when administered sequentially or 
co-administered with mRNA-1273 booster 
vaccination. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to the local study contact information document. 
4. Sponsor study contact for reporting of Serious Adverse Events (SAEs) 
Refer to Section 8.3.3.1. 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 1 21 September 2021  
This amendment is considered substantial based on the criteria defined in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it significantly impacts the scientific value of the study  
Overall rationale for the current Amendment: This amendment is intended to modify 
the dose of each mRNA-1273 booster injection to 50 mcg from 100 mcg. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
2.2 Background 
Moderna has been evaluating the use of 50 µg 
(half dose) or 100 µg (full dose) of mRNA-
1273 as a booster vaccine in participants 
previously vaccinated with 2 doses of 100 µg 
mRNA-1273 as a primary series. Available 
data indicates that boosting with half dose 
of the prototype mRNA-1273 has acceptable 
safety profile and induces robust 
neutralization titers against the Wuhan 
strain and variant viruses tested in all 
participants [Wu, 2021b]. It is however 
unclear if the half dose will sufficiently 
boost the immune response against other 
variants that are expected to emerge as the 
pandemic continues to evolve. Additional 
trials are underway to assess the safety and 
immunogenicity of different dose levels of 
the booster vaccines e.g.100 µg of mRNA-
1273 (clinicaltrials.gov: NCT04889209), as 
well as newly developed variant-specific 
vaccines (clinicaltrials.gov: NCT04927065).  
As of September 14th, 2021, the half dose (50 
µg) mRNA-1273 booster is one of the 
COVID-19 booster vaccines recommended 
in the UK, to be administered at least 6 
months after the primary series for certain 
populations at higher risk of severe COVID-
19 disease. [JCVI 2021] The half dose 
mRNA-1273 booster is under evaluation by 
other health agencies such as the European 
Medicines Agency and the US Food and 
Drug Administration. (Amended 21 
September 2021) 
Background for consideration of the 50 
µg dose of the mRNA-1273 vaccine. 

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Section # and title 
Description of change 
Brief rationale 
4.2 Scientific 
Rationale 
As of summer, 2021, vaccines against COVID-
19 in people ages 12 years and older have 
become an essential part of healthcare 
procedures to control the COVID-19 pandemic. 
With the emergence and spread of the 
SARS-CoV-2 virus variants that may not be 
sufficiently controlled by the primary 
vaccinations, periodic administration of 
booster COVID-19 vaccines after primary 
vaccination is either already recommended 
for specific populations or is under 
consideration by various health agencies. 
Amended to reflect the current 
regulatory environment. 
4.3 Justification of 
dose. 
Moderna’s mRNA-1273 vaccine is authorized 
for use in the U.S in adults 18 YOA and older 
under an EUA by the FDA and as a primary 
series of two 100 µg doses administered 1 
month apart. Doses of 100 µg and 50 µg of the 
same vaccine are being investigated as a 
potential booster dose to be administered 
following the primary series. Preliminary results 
have shown that a 50 µg mRNA-1273 booster 
dose at least 6 months following the primary 
series substantially increases neutralizing 
antibodies against the wildtype SARS-CoV-2 
virus and other tested variants, with a safety 
profile consistent with the known profile in 
earlier clinical trials [Wu, 2021b]. Currently, in 
light of the evolving emergence of SARS-CoV-2 
variants, it is anticipated that a booster vaccine 
may be is needed. The current available data 
suggests that 50 µg (half dose) of mRNA-
1273 may be sufficient to boost immune 
response against the existing variants. This 
half dose is now recommended for boosting 
in the UK for certain populations at high risk 
for severe disease, to be administered 6 
months post the primary series. This dose 
is also under review by other health 
agencies. As a result, 50 µg of mRNA-1273 
will be used in this study.  
To note: If a different dose of mRNA-1273 is 
approved and recommended for use as a 
booster in the US while the study is 
ongoing, the dose of mRNA-1273 booster in 
the study will be adjusted in the HZ/su and 
mRNA-1273 booster cohort to the approved 
dose. The sample size in this cohort will 
also be adjusted accordingly to ensure 
sufficient power to achieve the 
corresponding primary objectives with the 
adjusted dose. The data generated with the 
50 µg of mRNA-1273 booster will then be 
informative and add to the body of safety 
and immunogenicity data at this dose level.  
(Amended 21 September 2021) 
Justification of Moderna mRNA 1273 
booster dose reduction from 100 µg to 
50 µg. 

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Section # and title 
Description of change 
Brief rationale 
6.3.2 
Randomization to 
study intervention 
The stratification by age will be set to target 
ensure a minimum of 75 participants in the ≥ 
65 YOA stratum in each group.  
Due to a later than anticipated start to 
the study, potential elderly participants 
may have mostly already received their 
seasonal influenza vaccines and no 
longer be eligible. 
9.5.1 Sample size 
for HZ/su and 
mRNA-1273 study 
cohort 
Note: If the dose of mRNA-1273 booster is 
adjusted while the study is ongoing, the 
sample size will be compensated in this 
cohort to ensure that there are enough 
evaluable participants in each group. 
Unlike seasonal influenza 
unpredictability, we would still be able 
to continue the study and re-estimate 
sample size requirements for the HZ/su 
and mRNA-1273 study cohort and make 
details explicit in a subsequent 
protocol amendment. 
10.2.6 Adverse 
Events of Special 
Interest 
Any case of suspected, probable, or 
confirmed myocarditis, pericarditis, or 
myopericarditis should be reported as an 
AESI, even if it does not meet criteria per 
the CDC case definition. The event should 
also be reported as an SAE if it meets any 
seriousness criterion listed in Section 
10.2.2. The following CDC working case 
definition of myocarditis or pericarditis 
[Gargano, 2021] is provided as guidance. 
Text on AESI reporting of myocarditis 
and pericarditis made consistent with 
text in other Moderna protocols 
submitted to IND in past; thereby, also 
requiring moving from SAE section to 
AESI section in protocol. 
 

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
List of main changes in the protocol and their rationale: ........................................... 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 18 
1.1. 
Synopsis ..................................................................................................... 18 
1.2. 
Schema ...................................................................................................... 18 
1.3. 
Schedule of activities (SoA) ........................................................................ 19 
2. 
INTRODUCTION .................................................................................................... 26 
2.1. 
Study rationale ............................................................................................ 26 
2.2. 
Background ................................................................................................ 26 
2.3. 
Benefit/Risk assessment ............................................................................. 28 
2.3.1. 
Risk assessment and mitigation ................................................... 28 
2.3.2. 
Benefit assessment ..................................................................... 35 
2.3.3. 
Overall benefit/risk conclusion ..................................................... 35 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 35 
4. 
STUDY DESIGN .................................................................................................... 39 
4.1. 
Overall design ............................................................................................. 39 
4.2. 
Scientific rationale for study design ............................................................. 40 
4.2.1. 
Rationale for randomization ......................................................... 41 
4.3. 
Justification for dose ................................................................................... 41 
4.4. 
End of study definition ................................................................................. 42 
5. 
STUDY POPULATION ........................................................................................... 42 
5.1. 
Inclusion criteria .......................................................................................... 42 
5.2. 
Exclusion criteria ......................................................................................... 43 
5.2.1. 
Medical conditions ....................................................................... 43 
5.2.2. 
Prior/concomitant therapy ............................................................ 44 
5.2.3. 
Prior/concurrent clinical study experience .................................... 45 
5.2.4. 
Other exclusions .......................................................................... 45 
5.3. 
Lifestyle considerations ............................................................................... 45 
5.4. 
Screening failures ....................................................................................... 45 
5.5. 
Criteria for temporarily delaying randomization and/or study 
intervention administration .......................................................................... 45 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 46 
6.1. 
Study interventions administered ................................................................ 46 
6.2. 
Preparation, handling, storage, and accountability ...................................... 47 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 47 
6.3.1. 
Participant identification ............................................................... 47 
6.3.2. 
Randomization to study intervention ............................................ 47 
6.3.3. 
Intervention allocation to the participant ....................................... 48 
6.3.4. 
Blinding and unblinding ................................................................ 48 
6.3.4.1. 
Emergency unblinding ................................................ 48 
6.4. 
Study intervention compliance .................................................................... 48 

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6.5. 
Dose modification ....................................................................................... 48 
6.6. 
Continued access to study intervention after the end of the study ............... 48 
6.7. 
Treatment of overdose ................................................................................ 48 
6.8. 
Concomitant therapy ................................................................................... 49 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 49 
7.1. 
Discontinuation of study intervention ........................................................... 49 
7.1.1. 
Contraindications to subsequent study intervention 
administration .............................................................................. 50 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 50 
7.3. 
Lost to follow-up .......................................................................................... 51 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 52 
8.1. 
Immunogenicity assessments ..................................................................... 52 
8.1.1. 
Biological samples ....................................................................... 53 
8.1.2. 
Laboratory assays ....................................................................... 53 
8.1.3. 
Immunological read-outs .............................................................. 54 
8.1.4. 
Immunological correlates of protection ......................................... 55 
8.2. 
Safety assessments .................................................................................... 55 
8.2.1. 
Pre-intervention administration procedures .................................. 55 
8.2.1.1. 
Collection of demographic data .................................. 55 
8.2.1.2. 
Medical/Vaccination history ........................................ 55 
8.2.1.3. 
History-directed physical examination......................... 56 
8.2.1.4. 
Pregnancy test ........................................................... 56 
8.2.1.5. 
Warnings and precautions to administration of 
study intervention ....................................................... 56 
8.2.2. 
Study holding rules and safety monitoring .................................... 56 
8.2.2.1. 
Safety review team oversight and staggered 
randomization ............................................................. 56 
8.2.2.2. 
Study holding rules ..................................................... 57 
8.3. 
Adverse events (AEs), serious adverse events (SAEs) and other 
safety reporting ........................................................................................... 59 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 59 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 61 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies 
and other events .......................................................................... 61 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, 
pIMDs, study holding rules and pregnancies .............. 62 
8.3.4. 
Treatment of AEs ......................................................................... 62 
8.3.5. 
Participant card ............................................................................ 63 
8.3.6. 
Medical device deficiencies.......................................................... 63 
8.3.6.1. 
Detection, follow-up, and prompt reporting of 
medical device deficiency ........................................... 63 
8.3.6.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 63 
8.4. 
Pharmacokinetics ....................................................................................... 64 
8.5. 
Genetics ..................................................................................................... 64 
8.6. 
Biomarkers ................................................................................................. 64 
8.7. 
Immunogenicity assessments ..................................................................... 64 

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8.8. 
Health outcomes ......................................................................................... 64 
8.9. 
Study procedures during special circumstances ......................................... 64 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 65 
9.1. 
Statistical hypotheses ................................................................................. 65 
9.2. 
Analysis sets ............................................................................................... 66 
9.2.1. 
Criteria for elimination from analysis ............................................ 67 
9.3. 
Statistical analyses ..................................................................................... 68 
9.3.1. 
Statistical analysis plan ................................................................ 68 
9.3.2. 
General considerations ................................................................ 68 
9.3.3. 
Participants disposition ................................................................ 68 
9.3.4. 
Primary endpoints analysis .......................................................... 68 
9.3.4.1. 
Primary endpoints for HZ/su and mRNA1273 
booster study cohort ................................................... 68 
9.3.4.1.1. 
HZ/su immunogenicity post-dose 2 
(anti-gE antibodies)................................. 68 
9.3.4.1.2. 
mRNA-1273 booster 
immunogenicity (anti-S protein 
antibodies) .............................................. 69 
9.3.4.2. 
Primary endpoints for Flu D-QIV and mRNA-
1273 booster study cohort .......................................... 69 
9.3.4.2.1. 
Flu D-QIV immunogenicity (anti-HI 
antibodies) .............................................. 69 
9.3.4.2.2. 
mRNA-1273 booster 
immunogenicity (anti-S protein 
antibodies) .............................................. 69 
9.3.5. 
Secondary immunogenicity endpoints analyses ........................... 70 
9.3.5.1. 
Flu D-QIV immunogenicity (Anti-HI antibody 
SCRs) ......................................................................... 70 
9.3.5.2. 
Descriptive immune endpoints .................................... 70 
9.3.5.2.1. 
Anti-gE humoral immunogenicity 
at pre-vaccination and post-dose 2 
of HZ/su .................................................. 70 
9.3.5.2.2. 
mRNA-1273 booster dose 
humoral immunogenicity ......................... 71 
9.3.5.2.3. 
Flu D-QIV humoral 
immunogenicity ....................................... 72 
9.3.6. 
Secondary endpoints analyses .................................................... 72 
9.3.6.1. 
Solicited local and systemic AEs ................................ 73 
9.3.6.2. 
Unsolicited AEs .......................................................... 73 
9.3.6.3. 
SAEs .......................................................................... 73 
9.3.6.4. 
Potential Immune-mediated Diseases (for 
HZ/su and mRNA-1273 booster cohort only) .............. 74 
9.3.6.5. 
Adverse events of special interest .............................. 74 
9.3.6.6. 
Suspected HZ episodes (for HZ/su and mRNA-
1273 booster cohort only) ........................................... 74 
9.3.6.7. 
COVID-19 cases ........................................................ 74 
9.3.6.8. 
Pregnancies ............................................................... 74 
9.3.6.9. 
Withdrawals due to AEs and SAEs ............................. 74 
9.3.7. 
Exploratory endpoints analyses ................................................... 75 
9.3.8. 
Other analyses............................................................................. 75 

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9.3.8.1. 
Demography and baseline characteristics 
analyses ..................................................................... 75 
9.4. 
Interim analyses .......................................................................................... 76 
9.4.1. 
Sequence of analyses .................................................................. 76 
9.4.2. 
First interim analysis .................................................................... 76 
9.4.3. 
Final analysis ............................................................................... 77 
9.4.4. 
Statistical considerations for interim analysis ............................... 77 
9.5. 
Sample size determination .......................................................................... 77 
9.5.1. 
Sample size for HZ/su and mRNA-1273 study cohort .................. 78 
9.5.2. 
Sample size for Flu D-QIV and mRNA-1273 booster study 
cohort .......................................................................................... 79 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 81 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 81 
10.1.1. 
Regulatory and ethical considerations ......................................... 81 
10.1.2. 
Financial disclosure ..................................................................... 81 
10.1.3. 
Informed consent process ............................................................ 82 
10.1.4. 
Data protection ............................................................................ 82 
10.1.5. 
Committees structure ................................................................... 83 
10.1.6. 
Dissemination of clinical study data ............................................. 83 
10.1.7. 
Data quality assurance ................................................................ 84 
10.1.8. 
Source documents ....................................................................... 85 
10.1.9. 
Study and site start and closure ................................................... 85 
10.1.10. Publication policy ......................................................................... 86 
10.2. 
Appendix 2: Adverse events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 86 
10.2.1. 
Definition of an AE ....................................................................... 86 
10.2.1.1. Events meeting the AE definition ................................ 86 
10.2.1.2. Events NOT meeting the AE definition ........................ 87 
10.2.2. 
Definition of an SAE ..................................................................... 87 
10.2.3. 
Solicited events ............................................................................ 89 
10.2.3.1. Solicited local adverse events .................................... 89 
10.2.3.2. Solicited systemic events ............................................ 89 
10.2.4. 
Unsolicited AEs ............................................................................ 89 
10.2.5. 
Potential immune-mediated diseases .......................................... 90 
10.2.6. 
Adverse events of special interest ................................................ 94 
10.2.7. 
COVID-19 cases .......................................................................... 98 
10.2.8. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 98 
10.2.9. 
Events or outcomes not qualifying as AEs or SAEs ..................... 99 
10.2.9.1. Pregnancy .................................................................. 99 
10.2.10. Recording and follow-up of AEs, SAEs, AESIs, pIMDs, 
IMCs and pregnancies ................................................................. 99 
10.2.10.1. Time period for collecting and recording AEs, 
SAEs, AESIs, pIMDs, and IMCs ............................... 100 
10.2.10.2. Follow-up of AEs, SAEs, AESIs, pIMDs, and 
IMCs ......................................................................... 100 
10.2.10.2.1. Follow-up during the study .................... 100 
10.2.10.2.2. Follow-up after the participant is 
discharged from the study..................... 100 
10.2.10.2.3. Follow-up of pregnancies ...................... 100 

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10.2.10.3. Updating of SAE, AESI, pIMD, and pregnancy 
information after removal of write access to the 
participant’s eCRF .................................................... 101 
10.2.11. Assessment of intensity and toxicity ........................................... 101 
10.2.11.1. Assessment of intensity ............................................ 101 
10.2.11.2. Assessment of causality ........................................... 103 
10.2.11.3. Medically attended visits ........................................... 104 
10.2.11.4. Assessment of outcomes .......................................... 104 
10.2.12. Reporting of SAEs, AESIs, pIMDs, and pregnancies ................. 104 
10.2.12.1. Events requiring expedited reporting to PPD ............ 104 
10.2.12.2. Back-up system in case the electronic reporting 
system does not work ............................................... 105 
10.3. 
Appendix 3: Contraceptive guidance and collection of pregnancy 
information ................................................................................................ 106 
10.3.1. 
Definitions .................................................................................. 106 
10.3.1.1. Woman of childbearing potential (WOCBP) .............. 106 
10.3.1.1.1. Women not considered as women 
of childbearing potential ........................ 106 
10.3.2. 
Contraception guidance ............................................................. 107 
10.3.3. 
Collection of pregnancy information ........................................... 107 
10.3.3.1. Female participants who become pregnant .............. 107 
10.4. 
Appendix 4: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) ........................................................................................ 108 
10.4.1. 
Definition of medical device AE and adverse device effect 
(ADE) ......................................................................................... 108 
10.4.2. 
Definitions of a medical device SAE, serious adverse 
device effect, and unexpected serious adverse device 
effect .......................................................................................... 108 
10.4.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ................................................................... 109 
10.5. 
Appendix 5: Abbreviations and glossary of terms ...................................... 110 
10.5.1. 
List of abbreviations ................................................................... 110 
10.5.2. 
Glossary of terms ....................................................................... 112 
10.6. 
Appendix 6: Protocol Amendment Summary of Changes .......................... 116 
10.6.1. 
Document history ....................................................................... 116 
10.6.2. 
List of main changes in the protocol and their rationale .............. 116 
11. REFERENCES ..................................................................................................... 119 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of activities.............................................................................. 19 
Table 2 
Schedule of study intervention administration and blood sampling 
for the study groups ............................................................................... 22 
Table 3 
Study procedures to be performed during the follow-up period for 
each suspected HZ episode ................................................................... 23 
Table 4 
Intervals between study visits for HZ/su and mRNA-1273 booster 
cohort ..................................................................................................... 24 
Table 5 
Intervals between study visits for Flu D-QIV and mRNA-1273 
booster cohort ........................................................................................ 25 
Table 6 
Risks associated with study interventions and study procedures 
and risk mitigation strategies .................................................................. 29 
Table 7 
Study objectives and endpoints .............................................................. 35 
Table 8 
Study groups, intervention, and blinding ................................................. 40 
Table 9 
Study interventions administered (Amended 21 September 2021) ......... 46 
Table 10 
Laboratory assays .................................................................................. 53 
Table 11 
Molecular biology ................................................................................... 53 
Table 12 
Immunological read-outs ........................................................................ 54 
Table 13 
Study holding rules ................................................................................. 57 
Table 14 
Timeframes for collecting and reporting of safety information ................. 60 
Table 15 
Timeframes for submitting SAE, AESI, pIMD, and pregnancy 
reports to PPD........................................................................................ 62 
Table 16 
Contact information for reporting SAEs, AESIs, pIMDs, study 
holding rules and pregnancies ................................................................ 62 
Table 17 
Analysis sets .......................................................................................... 67 
Table 18 
Sample size calculations for HZ/su and mRNA-1273 booster 
study cohort ........................................................................................... 78 
Table 19 
Sample size calculations for Flu D-QIV and mRNA-1273 booster 
study cohort ........................................................................................... 80 
Table 20 
Study administrative structure ................................................................ 83 

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Table 21 
Solicited local adverse events ................................................................ 89 
Table 22 
Solicited systemic events ....................................................................... 89 
Table 23 
List of potential immune-mediated diseases (pIMDs) ............................. 91 
Table 24 
List of AESIs applicable to mRNA-1273 vaccine .................................... 94 
Table 25 
Intensity scales for AEs ........................................................................ 101 
Table 26 
Highly effective contraceptive methods ................................................ 107 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 40 
Figure 2 
Evaluations based on 28 participants in the co-administration 
group in HZ/su and mRNA-1273 booster cohort risk assessment 
curve based on the proposed safety holding rules .................................. 58 
Figure 3 
Evaluations based on 25 participants in the co-administration 
group in Flu D-QIV and mRNA-1273 booster cohort risk 
assessment curve based on the proposed safety holding rules .............. 59 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: 
The purpose of this study is to evaluate the safety and immunogenicity of 
GlaxoSmithKline Biologicals SA’s (GSK’s) herpes zoster (HZ) subunit (su) vaccine 
(hereafter referred to as HZ/su) and quadrivalent seasonal influenza vaccine (hereafter 
referred to as Flu D-QIV) when administered sequentially or simultaneously with 
ModernaTX, Inc.’s (hereby referred to as Moderna) messenger ribonucleic acid (mRNA)-
based vaccine booster (hereafter referred to as mRNA-1273 booster) against coronavirus 
disease 2019 (COVID-19). 
Periodic administration of booster vaccines after primary vaccination with COVID-19 
vaccines are under consideration by various health regulatory agencies to combat the 
possible waning efficacy of the primary series and the emergence of Severe Acute 
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants. It is therefore important to 
generate data to support simultaneous administration of mRNA-1273 booster with other 
routinely recommended vaccines to enhance vaccine coverage rates in the populations at 
high risk of vaccine-preventable diseases. (Amended 21 September 2021) 
Objectives and endpoints: 
Refer to Section 3, Table 7. 
1.2. 
Schema 
Refer to Section 4.1, Figure 1. 

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1.3. 
Schedule of activities (SoA) 
Table 1 
Schedule of activities 
Type of contact 
Pre-Vacc Visit 
1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 Phone Contact 1 Phone Contact 2 
Notes 
Timepoint 
HZ/suSeq 
-7 days Day 1 
Week 2 Week 4 
Week 6 Week 10 Week 14 
6 weeks post 
last dose 
24 weeks post 
last dose 
HZ/suCoAd 
Week 4 Week 8 Week 12 
 
 
FluD-QIVSeq 
Week 2 Week 4 
Week 6 
 
 
FluD-QIVCoAd 
Week 4 
 
 
 
 
Check inclusion/exclusion 
criteria 
● 
○ 
○ 
○ 
 
○ 
 
 
 
Applicable eligibility criteria to be 
checked prior to administering study 
intervention 
Informed consent 
● 
○ 
 
 
 
 
 
 
 
Informed consent to be reconfirmed at 
Visit 1 and updated in the database if 
there is a change from what is taken 
during pre-vaccination visit 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
Medical and vaccination history  
● 
○ 
 
 
 
 
 
 
 
Medical and vaccination history to be 
updated in the database if there is a 
change at Visit 1 from what is taken 
during pre-vaccination visit 
History directed physical 
examination; examine axillae 
and study intervention 
administration sites  
○ 
○ 
○ 
○ 
○ 
○ 
○ 
 
 
 
Check contraindications, 
warnings and precautions to 
study intervention 
administration 
 
○ 
○ 
○ 
 
○ 
 
 
 
 
Check criteria for temporary 
delay for study intervention 
administration 
 
○ 
○ 
○ 
 
○ 
 
 
 
 
Check criteria for temporary 
delay for randomization 
 
○ 
 
 
 
 
 
 
 
 

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Type of contact 
Pre-Vacc Visit 
1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 Phone Contact 1 Phone Contact 2 
Notes 
Timepoint 
HZ/suSeq 
-7 days Day 1 
Week 2 Week 4 
Week 6 Week 10 Week 14 
6 weeks post 
last dose 
24 weeks post 
last dose 
HZ/suCoAd 
Week 4 Week 8 Week 12 
 
 
FluD-QIVSeq 
Week 2 Week 4 
Week 6 
 
 
FluD-QIVCoAd 
Week 4 
 
 
 
 
Urine (or/and blood, as per 
local requirement) pregnancy 
test 
 
● 
● 
● 
 
● 
 
 
 
Performed during a vaccination visit, prior
to vaccination (see Section 8.2.1.4) 
Body temperature before study 
intervention administration 
 
● 
● 
● 
 
● 
 
 
 
The preferred location for measuring 
temperature will be the oral route 
Randomization 
 
● 
 
 
 
 
 
 
 
 
Treatment number allocation 
 
● 
● 
● 
 
● 
 
 
 
 
Study intervention 
administration 
 
Refer to Table 2 for the schedule for each group 
(●) 
 
 
 
 
Observation for at least 30 
minutes post-study intervention 
administration 
 
Refer to Table 2 for the schedule for each group 
(●) 
 
 
 
 
Recording of administered 
study treatment number 
 
Refer to Table 2 for the schedule for each group 
(●) 
 
 
 
 
Distribution of eDiaries and 
training participants to use 
 
○ 
○ 
○ 
○ 
○ 
 
 
 
 
Blood sampling for antibody 
determination 
 
Refer to Table 2 for blood sampling schedule for each group 
(●) 
 
 
 
HZ lesion sample (HZ/su and 
mRNA-1273 booster cohort 
only) 
Unscheduled visits (●) 
Refer to Table 3 for procedures to be 
followed 
Record any concomitant 
medications/vaccinations 
 
● 
● 
● 
● 
● 
● 
● 
● 
 
Record any intercurrent 
medical conditions (IMC) 
 
● 
● 
● 
● 
● 
● 
● 
● 
 
Phone contact for safety 
follow-up  
 
 
 
 
 
 
 
● 
● 
 

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Type of contact 
Pre-Vacc Visit 
1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 Phone Contact 1 Phone Contact 2 
Notes 
Timepoint 
HZ/suSeq 
-7 days Day 1 
Week 2 Week 4 
Week 6 Week 10 Week 14 
6 weeks post 
last dose 
24 weeks post 
last dose 
HZ/suCoAd 
Week 4 Week 8 Week 12 
 
 
FluD-QIVSeq 
Week 2 Week 4 
Week 6 
 
 
FluD-QIVCoAd 
Week 4 
 
 
 
 
Training participants to 
recognize signs and symptoms 
of HZ (HZ/su and mRNA-1273 
booster cohort only) 
 
○ 
○ 
○ 
○ 
○ 
○ 
 
 
 
Recording of solicited AEs: 
onset post-study intervention 
administration (day of and 
following 6 days) 
 
Refer to Table 2 for the schedule for each group 
(●) 
 
 
 
 
Review/Return of eDiary  
 
○ 
○ 
○ 
○ 
○ 
○ 
 
 
 
Recording of non-serious AEs 
within 30 days post-dosing 
 
● 
● 
● 
● 
● 
● 
 
 
 
Recording of SAEs, AESIs, 
COVID-19 cases, and 
pregnancies. In addition, pIMDs 
and suspected HZ episodes in 
the HZ/su and mRNA-1273 
booster cohort  
 
● 
● 
● 
● 
● 
● 
● 
● 
 
Recording of AEs/SAEs related 
to study participation, or SAEs 
related to concurrent 
GlaxoSmithKline 
medication/vaccine 
● 
● 
● 
● 
● 
● 
● 
● 
● 
To be recorded if the event onset occurs 
any time after signing the ICF 
Recording of withdrawals 
 
● 
● 
● 
● 
● 
● 
● 
● 
 
Study Conclusion 
 
 
 
 
 
 
 
 
● 
 
AE = adverse event; AESI = adverse event of special interest eDiary = electronic diary; HZ= Herpes Zoster; IMC = intercurrent medical condition; PCR = polymerase chain reaction; 
pIMD = potential immune mediated disease; SAE = serious adverse event  
Grey cells indicate the given activity is not planned for the corresponding timepoint(s) 
The double-line border following Phone contact 1 indicates an interim analysis 
● is used to indicate a study procedure that requires documentation in the individual electronic case report form 
○ is used to indicate a study procedure that does not require documentation in the individual electronic case report form 

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Table 2 
Schedule of study intervention administration and blood sampling for the study groups 
Study Groups 
Activity 
Day 1 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 14 
HZ/suSeq 
Vaccination 
mRNA-1273 booster (right deltoid) 
HZ/su (left 
deltoid) 
- 
- 
- 
HZ/su (left 
deltoid) 
- 
- 
Blood Draw 
15 mL 
15 mL 
15 mL 
15 mL 
- 
- 
- 
15 mL 
HZ/suCoAd 
Vaccination 
mRNA-1273 booster (right deltoid) and 
HZ/su (left deltoid) 
- 
- 
- 
HZ/su 
(left 
deltoid) 
- 
- 
- 
Blood Draw 
15 mL 
- 
15 mL 
- 
- 
- 
15 mL 
- 
FluD-QIVSeq 
Vaccination 
mRNA-1273 booster (right deltoid) 
Flu D-QIV (left 
deltoid) 
- 
- 
- 
- 
- 
- 
Blood Draw 
15 mL 
15 mL 
15 mL 
15 mL 
- 
- 
- 
- 
FluD-QIVCoAd 
Vaccination 
mRNA-1273 booster (right deltoid) and 
Flu D-QIV (left deltoid) 
- 
- 
- 
- 
- 
- 
- 
Blood Draw 
15 mL 
- 
15 mL 
- 
- 
- 
- 
- 
Preferred vaccination sites are listed in the table. 
Notes: Refer to Figure 1 for the schedule for each of the study groups. Blood sampling to be completed prior to study intervention administration. 

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Table 3 
Study procedures to be performed during the follow-up period for each suspected HZ episode 
Type of contact 
Visit HZ-1 
Contact HZ-2 Contact HZ-3 Contact HZ-4 
Contact HZ-5 Contact HZ-6 Contact HZ-7# 
Timepoints 
Day HZ-1 
Day HZ-8 
Day HZ-15 
Day HZ-22 
Day HZ-29^ 
Day HZ-43 
Day HZ-57# 
Perform clinical examination 
○ 
 
 
 
 
 
 
Recording of the HZ onset date by study staff/investigator 
● 
 
 
 
 
 
 
Collect HZ lesion samples* (3 replicate samples) for confirmation 
by PCR of a case of clinically diagnosed suspected HZ 
● 
 
 
 
 
 
 
Record detailed relevant clinical information including progression 
of the HZ case in eCRF by study staff/investigator 
● 
● 
● 
● 
● 
● 
● 
Record information regarding HZ related complications 
● 
● 
● 
● 
● 
● 
● 
Record concomitant medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
Record any other IMCs  
● 
● 
● 
● 
● 
● 
● 
Record any medical attention received for HZ or any HZ related 
complication** 
● 
● 
● 
● 
● 
● 
● 
eCRF = electronic case report form; HZ= Herpes Zoster; IMC = intercurrent medical condition; PCR= Polymerase Chain reaction 
Grey cells indicate the given activity is not planned for the corresponding timepoint(s) 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
*If during clinical evaluation at Visit HZ-1, the investigator determines that adequate rash samples are not present (that is <3 lesions present or only papules), the investigator has the 
option of collecting 3 additional samples, preferably within 7 days.  
**Complications of the HZ episode (for example, PHN, disseminated HZ, ophthalmic disease) should be recorded as AE/SAE, as appropriate 
^Participants with suspected HZ to be followed up at least till Day HZ 29 
# Phone contacts to continue once every 2 weeks till the rash is resolved. At the time of Last Participant Last Visit, if a participant has an ongoing HZ episode, they will be followed up 
till Day HZ-29. The investigator will note in the participant’s eCRF the end date of HZ rash and if any HZ-associated symptoms are still ongoing. 

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Table 4 
Intervals between study visits for HZ/su and mRNA-1273 booster cohort 
Interval 
Planned Visit Interval 
Allowed Interval Range* 
For HZ/suSeq group 
Pre-vaccination → Visit 1 
-7 days 
-14 days to Day 1 
Visit 1→Visit 2 
14 days  
14-21 days* 
Visit 1→Visit 3 
28 days 
25-35 days* 
Visit 2→Visit 4 
28 days 
25-35 days* 
Visit 2→Visit 5 
56 days 
49-83 days* 
Visit 5→Visit 6 
28 days 
25-35 days* 
Visit 5→Phone contact 1 
42 days 
42-49 days 
Visit 5→Phone contact 2 
168 days 
154-182 days 
For HZ/suCoAd group 
Pre-vaccination → Visit 1 
-7 days 
-14 days to Day 1 
Visit 1→Visit 2 
28 days 
25-35 days* 
Visit 1→Visit 3 
56 days 
49-83 days* 
Visit 3→Visit 4 
28 days 
25-35 days* 
Visit 3→Phone contact 1 
42 days 
42-49 days 
Visit 3→Phone contact 2 
168 days 
154-182 days 
*Participants may not be eligible for the HZ/su and mRNA-1273 Per Protocol Set (PPS) if the visits happen beyond this interval. Intervals between visits and phone contact do not affect 
HZ/su and mRNA-1273 PPS eligibility. 

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Table 5 
Intervals between study visits for Flu D-QIV and mRNA-1273 booster cohort 
Interval 
Planned Visit Interval 
Allowed Interval Range* 
For FluD-QIVSeq group 
Pre-vaccination → Visit 1 
-7 days 
-14 days to Day 1 
Visit 1→Visit 2 
14 days 
14-21 days* 
Visit 1→Visit 3 
28 days 
25-35 days* 
Visit 2→Visit 4 
28 days 
25-35 days* 
Visit 2→Phone contact 1 
42 days 
42-49 days 
Visit 2→Phone contact 2 
168 days 
154-182 days 
For FluD-QIVCoAd group 
Pre-vaccination → Visit 1 
-7 days 
-14 days to Day 1 
Visit 1→Visit 2 
28 days 
25-35 days* 
Visit 1→Phone contact 1 
42 days 
42-49 days 
Visit 1→Phone contact 2 
168 days 
154-182 days 
*Participants may not be eligible for the Flu D-QIV and mRNA-1273 PPS if the visits happen beyond this interval. Intervals between visits and phone contact do not affect Flu D-QIV 
and mRNA-1273 PPS eligibility. 

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2. 
INTRODUCTION 
2.1. 
Study rationale 
The purpose of this study is to evaluate the safety and immunogenicity of GSK’s HZ/su 
and Flu D-QIV when administered sequentially or simultaneously with Moderna’s 
mRNA-1273 booster against COVID-19. 
Periodic administration of booster vaccines after primary vaccination with COVID-19 
vaccines are under consideration by various health regulatory agencies to combat the 
possible waning efficacy of the primary series and the emergence of SARS-CoV-2 
variants. It is therefore important to generate data to support simultaneous administration 
of mRNA-1273 booster vaccine with other routinely recommended vaccines to enhance 
vaccine coverage rates in the populations at high risk of vaccine-preventable diseases. 
(Amended 21 September 2021) 
2.2. 
Background 
Varicella zoster virus (VZV) causes 2 distinct diseases, varicella (chickenpox) that occurs 
shortly after primary VZV infection and is characterized by systemic illness and a widely 
disseminated rash, and HZ (shingles) that occurs when VZV reactivates from latency and 
typically manifests as a localized, dermatomal rash. 
The typical HZ rash usually lasts 2 to 4 weeks accompanied by pain and pruritus. The 
most common complication of HZ is post-herpetic neuralgia (PHN), an ongoing and 
often debilitating pain that may persist for months or years [Johnson, 2010]. Other 
complications may include sight-threatening ocular involvement, neurologic disease, and 
cutaneous bacterial superinfection. About half of all HZ cases occur in individuals over 
the age of 60, and individuals who reach 85 YOA have a 50% chance of having HZ 
during their lifetime. Since the loss of VZV-specific T-cell responses as a result of aging 
is associated with a heightened susceptibility to HZ, vaccination plays an important role 
to reduce the risk of HZ in older adults.  
GSK’s HZ vaccine (commercially available as Shingrix) is a non-live, recombinant 
subunit vaccine and consists of the VZV-glycoprotein E (gE) as an active ingredient, 
together with the liposome-based adjuvant system (AS) 01B (AS01B). The liquid AS is 
used to reconstitute the lyophilized antigen immediately prior to administration. The 
AS01B consists of the immunostimulants MPL (3-O-desacyl-4’-monophosphoryl lipid A) 
and QS-21 (a saponin molecule purified from the bark extract of the Quillaja saponaria 
Molina tree), which are formulated in liposomes. HZ/su has been evaluated in older 
adults (≥50 YOA) and in adults (≥18 YOA) who are immunodeficient or 
immunosuppressed due to disease or therapy and was shown to be highly efficacious, 
elicit strong cellular and humoral immune responses and the reactogenicity and safety 
profile of the vaccine was acceptable [Bastidas, 2019, Cunningham, 2018; Cunningham, 
2016; Dagnew, 2019; Lal, 2015; López-Fauqued, 2019; López-Fauqued, 2021]. Shingrix 
is indicated in the U.S. for prevention of HZ in adults aged 50 years and older and in 
adults aged 18 years and older who are or will be at increased risk of HZ due to 
immunodeficiency or immunosuppression caused by known disease or therapy. 

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Influenza is an acute, highly contagious, respiratory disease caused by influenza viruses. 
There are 2 significant types of influenza (flu) virus that cause disease in humans: Types 
A and B. The influenza A and B viruses that routinely spread in people (human influenza 
viruses) are responsible for seasonal flu epidemics each year. Influenza is mainly spread 
through respiratory droplets and more significantly impacts older people, young children 
and people with underlying medical conditions. The illness is accompanied by fever and 
variable degrees of other systemic symptoms, ranging from mild fatigue to respiratory 
failure and death. Due to frequent genetic and antigenic changes in influenza viruses, 
seasonal vaccines are frequently reformulated with updated viral strains based on annual 
World Health Organization (WHO) recommendations. Annual influenza vaccination is an 
effective measure to reduce the risk of influenza infection and its complications. 
GSK’s Flu D-QIV (commercially available as Fluarix Quadrivalent) is indicated in the 
U.S. for active immunization for the prevention of disease caused by influenza A subtype 
viruses and type B viruses contained in the vaccine and is approved for use in persons 
aged 6 months and older. 
COVID-19 is caused by SARS-CoV-2 [Hu, 2020]. As of 26 July 2021, >194 million 
confirmed cases and >4 million deaths have been reported to the WHO [WHO, 2021]. 
Individuals >60 YOA with comorbidities are more likely to acquire severe respiratory 
disease requiring hospitalization. The pathogenesis of SARS-CoV-2 is still unfolding. 
COVID-19 is characterized by lymphopenia (and lymphocyte exhaustion) with cytokine 
storm seen in severe disease. A significant decrease in T-cells (including CD4+ and 
CD8+ T-cells), NK-cells and B-cells has been reported. It has been suggested that 
COVID-19 may result in impaired immune responses (either due to stress or 
lymphopenia), which may also trigger VZV reactivation and development of HZ [CDC, 
2021b; Cao, 2020; Wang, 2020; Tufan, 2020; Elsaie, 2020; Lee, 2021; Diez-Domingo, 
2021]. 
There are reports that SARS-CoV-2 re-infection can occur suggesting the potential need 
for re-immunization. In addition, the recent emergence of SARS-CoV-2 variants (such 
as-501Y.V1 [B.1.17] in the United Kingdom, 501Y.V2 [B.1.351] in South Africa, 
B.1.617.2 [Delta] in India, etc.) with higher transmission abilities have led to higher 
reports of COVID-19 cases. Preliminary data indicate that there may be a decrease in 
efficacy of the current existing vaccines against some emerging variants. A high vaccine 
coverage is needed to curb transmission and subsequent development of SARS-CoV-2 
variants [Fontanet, 2021; Dougherty, 2021]. 
Moderna’s mRNA-1273 COVID-19 vaccine is a novel mRNA-based vaccine 
encapsulated in a lipid nanoparticle (LNP) against SARS-CoV-2. The vaccine includes a 
single mRNA sequence encoding the pre-fusion stabilized Spike (S) protein of SARS-
CoV-2 (Wuhan strain). Two doses of 100 µg mRNA-1273 showed 94.1% efficacy at 
preventing COVID-19, including severe disease, and no safety concerns were identified 
[Baden, 2021;]. The U.S. Food and Drug Administration (FDA) has issued an Emergency 
Use Authorization (EUA) to permit the emergency use for active immunization to 
prevent COVID-19 in individuals 18 YOA and older. The duration of vaccine efficacy, 
impact of new SARS-CoV-2 variants on vaccine efficacy, and persistence of 
immunogenicity are still under investigation [Pegu, 2021; Doria-Rose, 2021; Wu, 2021a]. 

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Moderna has been evaluating the use of 50 µg (half dose) or 100 µg (full dose) of 
mRNA-1273 as a booster vaccine in participants previously vaccinated with 2 doses of 
100 µg mRNA-1273 as a primary series. Available data indicates that boosting with half 
dose of the prototype mRNA-1273 has acceptable safety profile and induces robust 
neutralization titers against the Wuhan strain and variant viruses tested in all 
participants [Wu, 2021b]. It is however unclear if the half dose will sufficiently boost 
the immune response against other variants that are expected to emerge as the 
pandemic continues to evolve. Additional trials are underway to assess the safety and 
immunogenicity of different dose levels of the booster vaccines e.g.100 µg of mRNA-
1273 (clinicaltrials.gov: NCT04889209), as well as newly developed variant-specific 
vaccines (clinicaltrials.gov: NCT04927065).  
As of September 14th, 2021, the half dose (50 µg) mRNA-1273 booster is one of the 
COVID-19 booster vaccines recommended in the UK, to be administered at least 6 
months after the primary series for certain populations at higher risk of severe 
COVID-19 disease. [JCVI, 2021] The half dose mRNA-1273 booster is under 
evaluation by other health agencies such as the European Medicines Agency and the 
US Food and Drug Administration. (Amended 21 September 2021) 
Please refer to the current Investigator’s Brochure (IB) for information regarding pre-
clinical and clinical studies of Shingrix and Fluarix Quadrivalent and mRNA-1273. 
2.3. 
Benefit/Risk assessment 
2.3.1. 
Risk assessment and mitigation 
Detailed information about the known and expected benefits and risks and expected 
adverse events (AEs) following administration of HZ/su, Flu D-QIV, and mRNA-1273 
vaccines can be found in their respective IBs. The important potential/identified risks and 
the mitigation strategy associated with study interventions and study procedures are listed 
in Table 6. 

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Table 6 
Risks associated with study interventions and study procedures and risk mitigation strategies 
Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study intervention: HZ/su 
Risk of potential immune-
mediated diseases 
(pIMDs) following 
administration of HZ/su 
pIMDs are a subset of AEs that include autoimmune diseases 
and other inflammatory and/or neurological disorders of interest 
which may or may not have an autoimmune etiology. To date, 
there is no evidence of an increased risk of pIMDs following 
vaccination with HZ/su in evaluated adults 50 YOA or older 
[López-Fauqued, 2019]. Based on the theoretical concern that 
vaccination with an adjuvanted vaccine containing potent 
immunostimulants may interfere with immunological self-
tolerance, pIMDs undergo special safety monitoring for all GSK 
vaccines containing Adjuvant Systems. 
Close monitoring of pIMDs will be conducted per 
study protocol and analysis of safety data generated 
through clinical trials and other sources. The 
potential risk of events of possible autoimmune 
etiology to occur is mentioned in the ICF. In addition, 
the ICF advises participants to contact the study 
doctor or study staff immediately, should any 
symptoms be considered of concern. pIMDs will be 
collected up to study end in HZ/su recipients.  
Guillain-Barré Syndrome 
(GBS) 
New available information on GBS emerged from a post-
marketing observational study where the risk of GBS following 
vaccination with HZ/su was assessed in adults aged 65 YOA or 
older enrolled in the Medicare health insurance in the US. An 
increased risk of GBS during the 42 days following vaccination 
was estimated as an excess of 3.13 cases per million doses 
administered. Based on the review of the accumulated body of 
the information that is currently available, GSK considers that the 
strength of the collective evidence is insufficient to determine a 
causal relationship between HZ/su vaccination and GBS, owing to 
substantial limitations and confounding variables.  
Close monitoring of GBS will be conducted per 
study protocol and analysis of safety data generated 
through clinical trials and other sources as part of 
pIMDs (including GBS). The potential risk of events 
of possible autoimmune etiology to occur is 
mentioned in the ICF. In addition, the ICF advises 
participants to contact the study doctor or study staff 
immediately, should any symptoms be considered of 
concern. pIMDs (including GBS) will be collected up 
to study end. 
Hypersensitivity reactions 
(including anaphylaxis) 
Hypersensitivity reactions may occur following exposure to 
allergens from a variety of sources including food, aeroallergens, 
venom, drugs and immunizations. Vaccines are a mixture of 
compounds and allergic sensitization can occur to any 
Administration of the study intervention is to be 
preceded by a review of the participant’s medical 
history (especially with regard to previous 
vaccination and possible occurrence of undesirable 

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Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
component. While cutaneous reactions, such as rash or urticaria, 
are common, anaphylactic reactions are very rare [Ruggeberg, 
2007]. 
events) and a history-directed clinical examination. 
Anaphylaxis following vaccine administration is a 
contraindication to subsequent vaccination. 
As with all injectable vaccines, appropriate medical 
treatment and supervision should always be readily 
available in case of an anaphylactic event following 
the administration of the study intervention. The 
onset of serious vaccine-related allergic symptoms 
is typically immediate. In order to assess and 
adequately treat participants who may have an 
allergic reaction to the study intervention, all 
participants will need to remain under observation 
(i.e. visibly followed; no specific procedure required) 
at the study clinic site for at least 30 minutes after 
each study intervention dose is administered. 
Study Intervention: Flu D-QIV 
Anaphylaxis 
Anaphylaxis is an acute, severe, multiorgan system reaction that 
can progress rapidly and be potentially fatal. It may occur 
following exposure to a variety of allergens, such as food, drugs, 
insect stings and vaccines. The most commonly involved organ 
systems include the respiratory, cardiovascular, cutaneous, and 
gastrointestinal systems. Signs and symptoms can include 
generalized urticaria, wheezing, swelling of the mouth and throat, 
difficulty breathing, vomiting, hypotension, decreased level of 
consciousness, and shock [CDC, 2010; Mustafa, 2012; 
Ruggeberg, 2007]. 
Hypersensitivity after previous administration of Flu 
D-QIV or influenza vaccines or to any component of 
the vaccine is a contraindication. It is general 
medical practice to observe patients for 30 minutes 
following vaccination for signs and symptoms of 
anaphylaxis. As with all injectable vaccines, 
appropriate medical treatment and supervision 
should always be readily available in case of a rare 
anaphylactic event following administration of the 
vaccine. Treatment given for anaphylaxis may 
include epinephrine, steroids, volume replacement 
therapy, and antihistamines [Ruggeberg, 2007]. 

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Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
GBS 
Progressive, bilateral, relatively symmetric flaccid paralysis, which 
develops over the course of hours or days up to 3 to 4 weeks, is 
the hallmark of GBS. The respiratory muscles including the 
diaphragm can be affected, and acute respiratory failure occurs in 
25% of patients [Yuki, 2012]. Sensory abnormalities and 
autonomic dysfunction can also occur [Haber, 2009]. Since 
launch, 83 cases of GBS were received corresponding to a 
spontaneous reporting frequency of 0.03 cases per 
100,000 doses distributed. Risk window generally highest within 
6-8 weeks after potential exposure. 
GBS is listed as rare adverse reaction in the 
labelling. There is no known prevention for GBS. 
Prompt initiation of plasmapheresis or 
immunoglobulin infusion may reduce disease 
severity and speed recovery. 
The ICF advises participants to contact the study 
doctor or study staff immediately, should any 
symptoms be considered of concern. 
Bell’s Palsy 
Abrupt onset of unilateral facial weakness or complete paralysis 
of all the muscles on one side of the face, dry eye, pain around 
the ear, an altered sense of taste, hyperacusis (hypersensitivity to 
sounds), or decreased tearing [Greco, 2012]. Most cases are 
idiopathic. Known associations with human immunodeficiency 
virus (HIV) infection, Lyme disease, sarcoidosis, Sjögren’s 
syndrome, acute otitis media, tumor, hypertension, diabetes 
mellitus, and trauma. Pregnancy and certain viral illnesses 
(especially herpes viruses) can also be associated with Bell’s 
palsy. Since launch, thirty-six (36) cases including the MedDRA 
PT term of facial paralysis or facial paresis were received, 
corresponding to a spontaneous reporting frequency of 0.01cases 
per 100,000 doses distributed. 
As the mechanism of action is not well-understood, 
there is no known way to prevent Bell’s palsy. Most 
cases resolve, either spontaneously (71%) [Greco, 
2012] or with treatment. 
The ICF advises participants to contact the study 
doctor or study staff immediately, should any 
symptoms be considered of concern. 
Study intervention: mRNA-1273 
Anaphylaxis 
These reactions are very rare and are estimated to occur once 
per 450,000 vaccinations for vaccines that do not contain 
allergens such as gelatin or egg protein [Zent, 2002]. Anaphylaxis 
As a precaution, all participants will remain under 
observation at the study site for at least 30 minutes 
after study intervention administration with medical 
attention available in case of anaphylaxis. 

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Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
has been reported following administration of mRNA-1273 
vaccine in the general public after Emergency Use Authorization. 
Vasovagal syncope 
Vasovagal or anxiety reactions such as syncope can occur before 
or after any vaccination, is usually triggered by the pain or anxiety 
caused by the injection and is not related to the substance 
injected. 
Study intervention will be administered with the 
participant in a seated position by a trained 
professional. As a precaution, all participants will 
remain under observation at the study site for at 
least 30 minutes after study intervention 
administration with medical attention available in 
case of vasovagal reactions.  
Intramuscular injection 
containing SM-102 lipid 
formulation 
Intramuscular injection with other mRNA vaccines manufactured 
by Moderna. containing the SM-102 lipid formulation commonly 
results in a transient and self-limiting local inflammatory reaction. 
This typically includes pain, erythema (redness), or swelling 
(hardness) at the injection site, which are mostly mild-to-moderate 
in severity and usually occur within 24 hours of vaccination. More 
severe, but self-limited, local reactions, erythema and induration, 
have been observed at dose of mRNA-1273 exceeding the dose 
proposed in this study. Most systemic adverse events observed 
after vaccination do not exceed mild-to-moderate severity. The 
most commonly reported systemic adverse reactions (ARs) are 
anticipated to be fever, fatigue, chills, headache, myalgias and 
arthralgias. More severe reactions, including erythema, 
induration, fever, headache and nausea, were reported after 
receiving doses of mRNA-1273 that were greater than the dose 
proposed for use in this study. In all cases, the reactions resolved 
spontaneously. 
The participants will be monitored for solicited AEs 
(Days 1-7) and unsolicited AEs (Days 1-30) 
following study intervention administration according 
to the protocol.  
The ICF advises participants to contact the study 
doctor or study staff immediately, should any 
symptoms be considered of concern 

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Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Vaccine-associated 
disease enhancement 
There is a theoretical risk that active vaccination to prevent the 
novel viral infection caused by SARS-CoV-2 may cause a 
paradoxical increase in the risk of disease. This possibility is 
based on the rare phenomenon of vaccine-associated disease 
enhancement which was first seen in the 1960s with 2 vaccines 
made in the same way (formalin-inactivated whole virus) and 
designed to protect children against infection with RSV [Chin, 
1969] or measles [Fulginiti, 1967]. Disease enhancement has 
also been proposed as a possible explanation for cases of more 
serious disease associated with dengue vaccination [Thomas, 
2019; WHO, 2018]. In Study P301, prespecified harm rules 
designed to detect an imbalance in cases of COVID-19 or severe 
COVID-19 were not met. Most importantly, after a median follow-
up of 2 months after the second dose of vaccine, the majority of 
COVID-19 cases occurred in participants who received placebo 
rather than mRNA-1273 [Baden, 2021], confirming no clinical 
evidence for vaccine-enhanced disease following vaccination with 
mRNA-1273. 
Available data so far since the vaccine received 
EUA do not indicate vaccine-associated disease 
enhancement as a safety concern. Participant’s 
safety data will be monitored as per protocol and will 
include suspected COVID-19 cases. 
Myocarditis or Pericarditis 
In the context of the EUA for individuals 18 and older for mRNA-
1273, there have been very rare reports of myocarditis and 
pericarditis occurring after vaccination with Moderna COVID-19 
Vaccine. Although causality has not been established, the 
majority of the cases have been reported in young males shortly 
after the second dose of the vaccine. These are typically mild 
cases and individuals tend to recover within a short time following 
standard treatment and rest [Gargano, 2021]. 
The ICF advises study participants about the 
symptoms of myocarditis and pericarditis, and to 
seek medical attention and contact the study doctor 
or study staff should any of these symptoms occur 
following study intervention administration. 

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Important 
Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study Procedures 
Risk from blood sampling 
Blood sampling associated risk of discomfort, syncope, dizziness, 
infection at the site after or during venipuncture. 
Blood samples will be obtained in seated or supine 
position by a trained professional and medical 
assistance will be available. 
The potential risk of feeling faint, or experiencing 
mild local pain, bruising, irritation or redness at the 
site where blood was taken, is mentioned in the ICF. 
The amount of blood to be taken for sampling will 
not be harmful to the participant’s health. 
Risk of lesion sampling 
(For HZ/su and mRNA-
1273 booster cohort only) 
Swab/needle sampling of lesions/crusts associated risk of 
secondary infection, and discomfort related to the procedure. 
Lesion samples will be obtained by a trained 
professional under aseptic conditions to minimize 
the potential for secondary infection. 
The potential risk of some temporary discomfort 
during the sampling procedure and the risk of 
infection are mentioned in the ICF. 
 

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2.3.2. 
Benefit assessment 
Symptoms directed physical examinations and clinical assessments that the participants 
will undergo during the study, will be made by trained clinical staff and can provide 
participants with valuable knowledge about their health (e.g., in case the study 
investigator discovers a medical condition unrelated to study treatment, the participant 
may be referred to the local healthcare system). By receiving HZ/su OR Flu D-QIV in 
this study, the participants are likely to be protected against HZ or influenza, respectively. 
2.3.3. 
Overall benefit/risk conclusion 
Considering the measures taken to minimize risk to participants participating in this 
study, the potential or recognized risks identified in association with the study vaccines 
and study procedures are justified by the potential benefits that may be afforded to the 
participants receiving these vaccines and by the value of the information to be gained. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 7 
Study objectives and endpoints 
Objectives 
Endpoints* 
Primary 
• 
To demonstrate the non-inferiority** of humoral 
immunogenicity of 2 doses of HZ/su when the first 
dose of HZ/su is co-administered with the mRNA-
1273 booster dose compared to HZ/su administered 
alone. 
• 
Anti-glycoprotein E (gE) antibody concentrations 
expressed as group geometric mean concentration 
(GMC) ratio at 1 month post-dose 2 of HZ/su (at 
Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd). 
• 
To demonstrate non-inferiority** of humoral 
immunogenicity of 1 dose of mRNA-1273 booster 
when the first dose of HZ/su is co-administered with 
the mRNA-1273 booster dose compared to 
mRNA-1273 booster dose administered alone. 
• 
Anti-S Protein antibody concentrations expressed as 
group GMC ratio§ at 1 month post mRNA-1273 
booster dose (at Week 4 for HZ/suSeq and 
HZ/suCoAd). 
• 
To demonstrate non-inferiority** of humoral 
immunogenicity of 1 dose of Flu D-QIV when 
co-administered with mRNA-1273 booster dose 
compared to Flu D-QIV administered alone based on 
geometric mean titer (GMT) of Flu D-QIV antibody 
titers against the 4 influenza strains. 
• 
Anti-hemagglutinin inhibition (HI) antibody titers 
expressed as group GMT ratio against the 4 
influenza strains included in Flu D-QIV at 1 month 
post Flu D-QIV (at Week 6 for FluD-QIVSeq,  
at Week 4 for FluD-QIVCoAd). 
• 
To demonstrate non-inferiority** of humoral 
immunogenicity of 1 dose of mRNA-1273 booster 
when co-administered with Flu D-QIV compared to 
mRNA-1273 booster dose administered alone. 
• 
Anti-S Protein antibody concentrations expressed as 
group GMC ratio§ at 1 month post mRNA-1273 
booster dose (at Week 4 for FluD-QIVSeq and  
FluD-QIVCoAd). 

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Objectives 
Endpoints* 
Secondary 
• 
To demonstrate the non-inferiority** of humoral 
immunogenicity of 1 dose of Flu D-QIV vaccine when 
co-administered with mRNA-1273 booster dose 
compared to Flu D-QIV administered alone based on 
seroconversion rate (SCR) difference of Flu D-QIV HI 
antibody titers against 4 influenza strains. 
• 
Anti-HI antibody SCR difference against the 4 
influenza strains at 1 month post Flu D-QIV (at Week 
6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). 
• 
To characterize the anti-gE humoral immunogenicity 
at pre-vaccination and at 1 month post-dose 2 of 
HZ/su. 
• 
Seropositivity rate with exact 95% CI at pre-
vaccination (at Day 1 for HZ/suCoAd, at Week 2 for 
HZ/suSeq) and at 1 month post-dose 2 of HZ/su (at 
Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd). 
• 
Anti-gE antibody concentrations expressed as GMC 
with 95% CI at pre-vaccination (at Day 1 for 
HZ/suCoAd, at Week 2 for HZ/suSeq) and at 1 month 
post-dose 2 of HZ/su (at Week 14 for HZ/suSeq, at 
Week 12 for HZ/suCoAd). 
• 
Vaccine response rate (VRR) with exact 95% CIs at 1 
month post-dose 2 of HZ/su (at Week 14 for 
HZ/suSeq, at Week 12 for HZ/suCoAd).  
• 
Mean geometric increase (MGI) from pre-vaccination 
with 95% CI at 1 month post-dose 2 of HZ/su (at 
Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd). 
• 
To characterize the humoral immunogenicity of 
mRNA-1273 booster dose. 
• 
Anti-S Protein antibody concentrations expressed as 
GMC§ with 95% CI at pre-vaccination (Day 1) and 1 
month post mRNA-1273 booster dose (at Week 4 for 
all groups). 
• 
MGI§ from pre-vaccination with 95% CI at 1 month 
post mRNA-1273 booster dose (at Week 4 for all 
groups). 
• 
To evaluate the humoral immunogenicity of Flu D-
QIV. The assessment of SPR and SCR will be based 
on Center for Biologics Evaluation and Research’s 
(CBER) criteria***. 
• 
Anti-HI antibody titers against the 4 influenza strains 
included in Flu D-QIV expressed as GMTs with 95% 
CI at pre-vaccination and at 1 month post Flu D-QIV 
(at Week 6 for FluD-QIVSeq, at Week 4 for 
FluD-QIVCoAd). 
• 
Seroprotection rate (SPR) with exact 95% CI at pre-
vaccination and at 1 month post Flu D-QIV (at Week 
6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd), 
overall and by age category (18-64 and ≥65 YOA). 
• 
Seropositivity rate with exact 95% CI at pre-
vaccination and at 1 month post Flu D-QIV (at Week 
6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). 
• 
MGI with 95% CI from pre-vaccination at 1 month 
post Flu D-QIV (at Week 6 for FluD-QIVSeq, at Week 
4 for FluD-QIVCoAd). 
• 
SCR with exact 95% CI from pre-vaccination at 1 
month post Flu D-QIV (at Week 6 for FluD-QIVSeq, 
at Week 4 for FluD-QIVCoAd), overall and by age 
category (18-64 and ≥65 YOA). 

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Objectives 
Endpoints* 
• 
To evaluate the safety and reactogenicity following 
administration of HZ/su, Flu D-QIV and mRNA-1273 
booster dose, up to 30 days post-last vaccination and 
during the whole post-vaccination follow-up period.  
• 
Solicited adverse events (AEs): Number and 
percentage of participants reporting each solicited 
local AE and each solicited systemic AE within 7 
days (Days 1-7) after each dose and overall. 
• 
Unsolicited AEs: 
- 
Number and percentage of participants 
reporting unsolicited AEs within 14 days  
(Days 1-14) after each vaccination visit and 
overall after any vaccination visit for all groups. 
- 
Number and percentage of participants 
reporting unsolicited AEs within 30 days  
(Days 1-30) after each vaccination visit and 
overall after any vaccination visit for all groups. 
• 
Serious adverse events (SAEs):  
- 
Number and percentage of participants 
reporting SAEs from first dose up to 30 days 
post-last dose within each group. 
- 
Number and percentage of participants 
reporting SAEs from first dose to study end. 
• 
Potential immune mediated diseases (pIMDs) in 
HZ/su and mRNA-1273 booster cohort only:  
- 
Number and percentage of participants 
reporting of pIMDs from first dose up to 30 days 
post-last dose within each group. 
- 
Number and percentage of participants 
reporting pIMDs from first dose to study end. 
• 
Adverse events of special interest (AESIs):  
- 
Number and percentage of participants reporting 
AESIs from first dose up to 30 days post-last 
dose within each group. 
- 
Number and percentage of participants reporting 
AESIs from first dose to study end. 
• 
Suspected HZ episodes in HZ/su and mRNA-1273 
booster cohort only: Number and percentage of 
participants reporting clinically suspected HZ 
episodes from first dose to study end. 
• 
COVID-19 cases: Number and percentage of 
participants meeting case definitions of COVID-19 
from first dose to study end. 
Exploratory 
• 
To evaluate the incidence of lab-confirmed HZ 
episodes following administration of HZ/su during the 
whole follow-up period.  
• 
Confirmed HZ cases in HZ/su and mRNA-1273 
booster cohort only: Number and percentage of 
participants with polymerase chain reaction (PCR) 
confirmed HZ episodes from first vaccination to study 
end. 
• 
To characterize the anti-gE humoral immunogenicity 
at 1 month post-dose 1 of HZ/su. 
• 
Seropositivity rate with exact 95% CI at 1 month post-
dose 1 of HZ/su (at Week 6 for HZ/suSeq, at Week 4 
for HZ/suCoAd).  

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Objectives 
Endpoints* 
• 
Anti-gE antibody concentrations expressed as 
GMC with 95% CI at 1 month post-dose 1 of HZ/su (at 
Week 6 for HZ/suSeq, at Week 4 for HZ/suCoAd).  
• 
VRR with exact 95% CIs at 1 month post-dose 1 of 
HZ/su (at Week 6 for HZ/suSeq, at Week 4 for 
HZ/suCoAd).  
• 
Mean geometric increase (MGI) from pre-vaccination 
with 95% CI at 1 month post-dose 1 of HZ/su (at 
Week 6 for HZ/suSeq, at Week 4 for HZ/suCoAd).  
• 
To further evaluate the immune response to the 
mRNA-1273 booster vaccine via neutralizing 
antibody titers in a sub-cohort of participants in all 
study groups.  
• 
GMT with 95% CIs of SARS-CoV-2 neutralizing 
antibody titers in a sub-cohort of participants in each 
study group at pre-vaccination and at 1 month post 
mRNA-1273 booster dose (Week 4 for all groups). 
• 
To evaluate further SARS-CoV-2/mRNA-1273 
immune responses during the study. 
• 
GMCs with 95% CI of anti-receptor binding domain 
(RBD) protein antibodies at pre-vaccination and 1 
month post mRNA-1273 booster dose (at Week 4 for 
all groups). 
• 
Anti-nucleocapsid (N) protein seroconversion rate 
with exact 95% CI from pre-vaccination to 1 month 
post mRNA-1273 booster dose (at Week 4 for all 
groups). 
§Pending final assay evaluations and validations prior to study specimen testing, this primary endpoint for all 
participants may be replaced with SARS-CoV-2 neutralizing antibody titers, and where applicable derived GMTs, GMT 
ratios, and MGI. 
*The definitions and derivations of endpoint parameters are presented in Section 9.4. 
**The success criteria for primary objectives and secondary objectives are presented in Section 9.1.  
***CBER criteria are presented in Section 9.3.5.2.3 
# It should be noted that participants in the HZ/suSeq and FluD-QIVSeq groups will receive their HZ/su or Flu D-QIV, 
respectively, at Day 14 post mRNA booster vaccine dose at Day 1. 
 Case Definitions in section 10.2.7 
Details related to attributes of endpoint covering intercurrent events, population and 
treatment definition are provided in Section 9. 

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4. 
STUDY DESIGN 
4.1. 
Overall design 
This study is a Phase III, randomized, open-label, controlled, multicenter US-based study 
to evaluate the immune response and safety of both HZ/su in healthy adults 50 YOA and 
older and Flu D-QIV in healthy adults 18 YOA and older when administered sequentially 
or co-administered with mRNA-1273 booster vaccination. 
The study will be conducted in the U.S. and will enroll participants in 2 main study 
cohorts, HZ/su with mRNA-1273 booster vaccine administered sequentially or 
concomitantly and Flu D-QIV with mRNA-1273 booster vaccine administered 
sequentially or concomitantly, hereafter entitled HZ/su and mRNA-1273 booster cohort 
and Flu D-QIV and mRNA-1273 booster cohort, respectively (Figure 1). 
Potential participants will be triaged initially to either study cohort (HZ/su and mRNA-
1273 booster, Flu D-QIV and mRNA-1273 booster) based upon criteria such as seasonal 
influenza vaccine availability, known eligibility criteria (such as age and vaccination 
history), and current study enrollment status. Subsequently, enrolled (i.e., having signed 
an informed consent form) and eligible participants in each cohort will be randomized in 
a 1:1 ratio to each of the 2 study groups within each cohort (Table 8). Staggered 
randomization will be implemented at the beginning of the study for safety monitoring 
(see Section 8.2.2.1). 
• 
In the HZ/su and mRNA-1273 booster cohort, 546 participants will be randomized in 
a 1:1 ratio so that 273 participants are assigned to each study group. The first group 
(HZ/suSeq group) will receive the mRNA-1273 booster dose followed 
approximately 2 weeks later by the first dose of HZ/su, while the second group 
(HZ/suCoAd group) will receive the mRNA-1273 booster dose co-administered 
with the first dose of HZ/su. All participants in the HZ/suSeq group and the 
HZ/suCoAd group will receive the second dose of HZ/su approximately 2 months 
after the first HZ/su dose. Randomization into each group will be stratified by age 
(50 to 59, 60 to 69, and ≥ 70 YOA) and will be set to ensure a minimum number of 
138 participants are assigned to the ≥ 70 YOA stratum, 69 participants to each group. 
• 
In the Flu D-QIV and mRNA-1273 booster cohort, 1000 participants will be 
randomized in a 1:1 ratio so that 500 participants are assigned to each study group. 
The first group (FluD-QIVSeq group) will receive the mRNA-1273 booster dose 
followed approximately 2 weeks later by the Flu D-QIV dose, while the second 
group (FluD-QIVCoAd group) will receive the mRNA-1273 booster dose co-
administered with the Flu D-QIV dose. Randomization into each group will be 
stratified by age (18 to 64 and ≥ 65 YOA) and will be set to target (Amended 21 
September 2021) a minimum number of 150 participants are assigned to the ≥ 65 
YOA stratum, 75 participants to each group. 
All study participants will be followed for safety until 6 months post the last dose of the 
study vaccine with the total duration of study participation approximately 34 and 26 
weeks in the HZ/su and mRNA-1273 booster cohort and Flu D-QIV and mRNA-1273 
booster cohort, respectively. 

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Figure 1 
Study design overview 
 
EOS = end of study, telephone contact at 24 weeks post last vaccine dose; N = number of participants enrolled and 
randomized; PLD = post last dose 
*Safety Review Team evaluation of 7 days post-dosing after Visit 1 safety data for initial 10% vaccinated in the 
HZ/suCoAd group and 5% vaccinated in the FluD-QIVCoAd group prior to full randomization in the respective cohorts  
(Amended 21 September 2021) 
Table 8 
Study groups, intervention, and blinding 
Cohort 
Study Groups 
Number of 
Randomized 
Participants 
Age 
 
Study 
Interventions 
Blinding 
Visit 1 → Phone 
Contact 2 
(Open-label)* 
HZ/su and 
mRNA1273 
Booster 
HZ/suSeq 
273 
≥50 years** 
mRNA-1273 
booster 
HZ/su 
x 
HZ/suCoAd 
273 
Flu D-QIV and 
mRNA-1273 
Booster 
FluD-QIVSeq 
500 
≥18 years** 
mRNA-1273 
booster 
Flu D-QIV 
x 
FluD-QIVCoAd 
500 
*This is an open-label study; however, the specific participant vaccination schedule (sequential or coadministration) will 
be randomly assigned within each cohort. 
** Randomization will be set to ensure at least 69 participants per group will be ≥ 70 YOA in the HZ/su and mRNA-
1273 booster cohort and to target at least 75 participants ≥ 65 YOA per group in the Flu D-QIV and mRNA-1273 
booster cohort. (Amended 21 September 2021) 
4.2. 
Scientific rationale for study design 
The study was designed after careful considerations of the current healthcare needs and 
expectations related to vaccinations of the adult population in the U.S. 
The U.S Centers for Disease Control and Prevention (CDC) recommends receipt of 
Shingrix to everyone 50 YOA and older, to prevent shingles and its complications [CDC, 
2019]. 

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According to CDC, everyone 6 months of age and older should receive a seasonal 
influenza vaccine every season with rare exceptions. For 2021-2022, CDC recommends 
use of any licensed, influenza vaccine that is appropriate for the recipient’s age and 
health status, including inactivated influenza vaccine, recombinant influenza vaccine, or 
live attenuated nasal spray influenza vaccine [CDC, 2021a]. 
As of summer, 2021, vaccines against COVID-19 in people ages 12 years and older have 
become an essential part of healthcare procedures to control the COVID-19 pandemic. 
With the emergence and spread of the SARS-CoV-2 virus variants that may not be 
sufficiently controlled by the primary vaccinations, periodic administration of booster 
COVID-19 vaccines after primary vaccination is either already recommended for 
specific populations or is under consideration by various health agencies. (Amended 21 
September 2021) 
Current CDC guidance on the coadministration of COVID-19 vaccines with other routine 
vaccinations is as follows: “COVID-19 vaccines and other vaccines may now be 
administered without regard to timing. This includes simultaneous administration of 
COVID-19 vaccine and other vaccines on the same day, as well as coadministration 
within 14 days. It is unknown whether reactogenicity of COVID-19 vaccine is increased 
with coadministration, including with other vaccines known to be more reactogenic, such 
as adjuvanted vaccines or live vaccines” [CDC, 2021c]. 
The current study is designed to provide reactogenicity, safety, and immunogenicity data 
for when a seasonal influenza virus vaccine or an adjuvanted Herpes Zoster subunit 
vaccine is administered at the same time or two weeks following a potential COVID-19 
mRNA booster vaccine. This is important needed data expected to help public health 
authorities provide more evidence-based guidance and health care providers to make 
decisions on such vaccine coadministrations. 
4.2.1. 
Rationale for randomization 
This will be an open-label study. Comparative analyses between the 2 study groups will 
only be conducted within each study cohort; therefore, once participants have been 
triaged to their study cohort, to prevent any selection bias in assignment to each study 
group, they will be randomly assigned to either the co-administration or sequential study 
group. Consequently, neither study staff nor participants will be aware which group the 
participant will be assigned to prior to the randomization. 
4.3. 
Justification for dose 
Fluarix Quadrivalent and Shingrix are vaccines licensed by the FDA for use in the U.S 
and shall be administered in this study as per their approved doses and schedule. 
Moderna’s mRNA-1273 vaccine is authorized for use in the U.S in adults 18 YOA and 
older under an EUA by the FDA and as a primary series of two 100 µg doses 
administered 1 month apart. Doses of 100 µg and 50 µg of the same vaccine are being 
investigated as a potential booster dose to be administered following the primary series. 
Preliminary results have shown that a 50 µg mRNA-1273 booster dose at least 6 months 
following the primary series substantially increases neutralizing antibodies against the 
wildtype SARS-CoV-2 virus and other tested variants, with a safety profile consistent 

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with the known profile in earlier clinical trials [Wu, 2021b]. Currently, in light of the 
evolving emergence of SARS-CoV-2 variants, it is anticipated that a booster vaccine may 
be needed. The current available data suggests that 50 µg (half dose) of mRNA-1273 
may be sufficient to boost immune response against the existing variants. This half 
dose is now recommended for boosting in the UK for certain populations at high risk 
for severe disease, to be administered 6 months post the primary series. This dose is 
also under review by other health agencies. As a result, 50 µg of mRNA-1273 will be 
used in this study.  
To note: If a different dose of mRNA-1273 is approved and recommended for use as a 
booster in the US while the study is ongoing, the dose of mRNA-1273 booster in the 
study will be adjusted in the HZ/su and mRNA-1273 booster cohort to the approved 
dose. The sample size in this cohort will also be adjusted accordingly to ensure 
sufficient power to achieve the corresponding primary objectives with the adjusted 
dose. The data generated with the 50 µg of mRNA-1273 booster will then be 
informative and add to the body of safety and immunogenicity data at this dose level. 
(Amended 21 September 2021) 
4.4. 
End of study definition 
A participant is considered to have completed the study if he/she is available for the last 
scheduled contact as described in the protocol. 
The End of Study is defined as the date of the Last Participant Last Visit (LPLV, also 
may appear as last subject last visit, LSLV) or date of last testing results released of the 
Human Biological Samples related to primary and secondary endpoints, whichever 
comes last. End of Study must be achieved no later than 8 months after the LPLV. 
5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardize the scientific 
integrity, regulatory acceptability of the study, or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
• 
Participants who in the opinion of the investigator, can and who will comply with the 
requirements of the protocol (e.g., completion of the eDiaries, return for follow-up 
visits). 
• 
Written informed consent obtained from the participant prior to performance of any 
study-specific procedure.  
• 
Age at study entry:  
− 
For HZ/su and mRNA-1273 booster cohort: A male or female aged 50 years or 
older at the time of randomization. 
− 
For Flu D-QIV and mRNA-1273 booster cohort: A male or female aged 18 
years or older at the time of enrollment. 

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• 
Healthy participants or medically stable patients as established by medical history 
and clinical examination at screening. A stable medical condition is defined as 
disease not requiring significant change in therapy or hospitalization for worsening 
disease during the 3 months before enrolment. 
• 
Participants who have a documented previous mRNA-1273 primary vaccination 
series completed (i.e., both doses) at least 6 months prior to first vaccination. 
• 
Female participants of non-childbearing potential (see definition in Section 10.3) 
may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, 
current bilateral tubal ligation or occlusion, documented total hysterectomy, bilateral 
ovariectomy, or bilateral salpingectomy, or post-menopause. Refer to Section 10.3.1 
for definitions of women of childbearing potential (WOCBP), menarche and 
menopause. 
• 
Female participants of childbearing potential may be enrolled in the study, if the 
participant:  
− 
Has practiced effective contraception (see definition in Section 10.3) for 1 
month prior to study intervention administration, and 
− 
Has a negative pregnancy test on the day of study intervention administration, 
and 
− 
Has agreed to continue effective contraception during the study until 2 months 
after completion of the study vaccination series. 
Refer to Section 10.3.1 for definition of WOCBP and adequate contraception. 
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MAY NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
Any clinical condition that, in the opinion of the investigator, might pose additional 
risk to the participant due to participation in the study or might confound post-study 
intervention administration safety assessments (e.g., tattoos overlying either study 
intervention administration site).  
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions, including a known history of severe allergic 
reaction (e.g., anaphylaxis) to any component of any of the study vaccines. 
• 
Any history of Guillain-Barré syndrome. 
• 
Any history of myocarditis or pericarditis. 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by medical history or physical examination. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
Hypersensitivity to latex. 
• 
For HZ/su and mRNA-1273 booster cohort: history of Herpes Zoster. 

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5.2.2. 
Prior/concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study intervention(s) during the period beginning 30 days 
before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use 
during the study period. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before first dose and ending 30 days after the 
last dose of study intervention administration. However, for HZ/su and mRNA-1273 
booster cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., 
inactivated and subunit vaccines, including inactivated and subunit influenza 
vaccines, with or without adjuvant for seasonal or pandemic flu) may be 
administered up until 8 days prior to dose 1 of HZ/su and/or dose 2 of HZ/su and/or 
at least 14 days after any dose of HZ/su. For Flu D-QIV and mRNA-1273 booster 
cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., 
inactivated and subunit vaccines, other than influenza vaccines) may be administered 
up until 8 days prior to dose 1 of Flu D-QIV and/or at least 30 days after any dose of 
Flu D-QIV. For time interval between other routine vaccines with mRNA-1273 
booster dose (administered in the study), local guidelines must be followed.  
In case emergency mass vaccination for an unforeseen public health threat (e.g., a 
pandemic) is organized by public health authorities outside the routine immunization 
program, the time period described above can be reduced if necessary for that mass 
vaccination vaccine, provided this vaccine is licensed and used according to its 
Product Information.  
• 
Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g., infliximab).  
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study intervention(s) up 
to 1 month post-last dose or planned administration during the study period. 
• 
Prior planned or chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 3 
months prior to the first vaccine. For corticosteroids, this will mean more than 14 
days in total of prednisone ≥20 mg/day or equivalent is not allowed. Inhaled, intra-
articular and topical steroids are allowed. 
• 
For HZ/su and mRNA-1273 booster cohort: Previous vaccination against Herpes 
Zoster with the exception of receipt of live attenuated HZ vaccine. 
• 
For Flu D-QIV and mRNA-1273 booster cohort: Administration of a seasonal 
influenza vaccine during the 6 months preceding entry into the study. 
• 
Prior administration of an investigational or licensed coronavirus (SARS-CoV, 
MERS-CoV, SARS-CoV-2) vaccine except for mRNA-1273 vaccine. 
• 
Any contraindication to the study intervention(s). 

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5.2.3. 
Prior/concurrent clinical study experience 
• 
Planning to or concurrently participating in another clinical study (including current / 
planned simultaneous participation in another interventional study to prevent or treat 
COVID-19), at any time during the study period, in which the participant has been or 
will be exposed to an investigational or a non-investigational vaccine / product (drug 
or medical device) (see the definitions in the Glossary of terms). 
5.2.4. 
Other exclusions 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions within 2 months following last study vaccination. 
• 
Indications of drug abuse or excess alcohol use as deemed by investigator to 
potentially confound safety assessments or render participant unable or unlikely to 
adhere to protocol requirements. 
Refer to Section 5.5 for criteria for temporary delay of enrollment and/or interventions. 
5.3. 
Lifestyle considerations 
Not applicable. 
5.4. 
Screening failures 
Screen failures are defined as participants who consented to participate in the clinical 
study but were not subsequently randomized. Screen failures will be listed in the source 
data and entered in the eCRF. 
A participant who failed screening or was unable to complete screening during the 
allowed window can be re-screened later at the discretion of the investigator and 
following GSK approval. 
5.5. 
Criteria for temporarily delaying randomization and/or study 
intervention administration 
Randomization/study intervention administration may be postponed within the permitted 
time interval until transient conditions cited below are resolved and the participant stays 
eligible: 
• 
Acute disease and/or fever at the time of randomization and/or study intervention 
administration. Fever is defined as temperature ≥ 38.0°C (100.4°F) by any route. The 
preferred location for measuring temperature will be oral route. 
• 
Participants with a minor illness without fever may be enrolled and/or dosed at the 
discretion of the investigator. 
• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 

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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to the Glossary of terms for the definition of study intervention. 
6.1. 
Study interventions administered 
Table 9 
Study interventions administered (Amended 21 September 2021) 
Study Intervention Name: 
HZ/su 
Flu D-QIV 
mRNA-1273 
Product Name: 
VZV gE 
AS01B 
Flu D-QIV 2021-2022 NH 
COVID-19 mRNA Vaccine 
Study intervention 
Formulation: 
VZV gE (50 µg) 
AS01B: QS-21 (50 µg), 
MPL (50 µg), liposomes; 
water for injections q.s. 
0.5 mL 
Flu Quadrivalent Influenza vaccine 
15 µg per strain*/dose 
100 µg per dose (embedded in SM-102 
lipid nanoparticles); water for 
injections q.s. 0.5 mL 
Formulation Dose Form: 
Powder for suspension for 
injection 
Suspension for injection 
Suspension for injection 
Dispersion for injection 
Presentation: 
Vial 
Vial 
Syringe 
Vial 
Product Category: 
Biologic 
Combination product 
Biologic 
Type: 
Study Vaccine 
Study Vaccine 
Study Vaccine 
Route of Administration: 
Intramuscular injection 
Intramuscular injection 
Intramuscular injection 
Administration Site: 
Left deltoid 
Left deltoid 
Right deltoid 
Number of Doses to be 
Administered: 
2 
1 
1 
Volume to be Administered**: 
0.5 mL 
0.5 mL 
0.25 mL 
Packaging and labeling: 
Refer to the Pharmacy Manual 
Manufacturer: 
GSK 
GSK 
Moderna 
HZ/su = herpes zoster subunit vaccine; VZV = varicella zoster virus; gE = glycoprotein E; AS01B = adjuvant system 01B; NH = North hemisphere; QS-21 = Quillaja saponaria Molina, 
fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of Agenus Inc., a Delaware, USA corporation); MPL = 3-O-desacyl-4’-monophosphoryl lipid A; q.s. = 
quantum satis 
* A/Victoria/2570/2019 (H1N1), IVR-215 (15 µg HA); A/Tasmania/503/2020 (H3N2), IVR-221 (15 µg HA); B/Washington/02/2019 (15 µg HA); B/Phuket/3073/2013 (15 µg HA); Water 
for injections q.s. 0.5 mL  
**Refer to the Pharmacy Manual for more details  

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Study participants must be observed closely for at least 30 minutes after the 
administration of the study interventions. The duration of the observation period can be 
extended at the investigator’s discretion. Appropriate medical treatment must be readily 
available during the observation period in case of significant hypersensitivity reactions, 
anaphylaxis, or syncope. 
6.2. 
Preparation, handling, storage, and accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a PPD study contact during pre-study activities. 
Refer to the Pharmacy Manual for more details on storage and handling of the study 
interventions. 
6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
At enrollment, participant identification numbers (IDs, may also be referred to as Subject 
Number) will be assigned sequentially to the participants who consented to participate in 
the study according to the range of participant IDs allocated to each study center. The IDs 
will be assigned upon site’s completion of the screening form in Interactive Web 
Response System through Interactive Response Tool (IRT). 
6.3.2. 
Randomization to study intervention 
Within each cohort, participants will be centrally randomized to 1 of the 2 study groups 
(sequential or co-administration) and receive a Randomization Number through IRT. At 
randomization, the IRT system will validate the participant’s age. Participants in the 
HZ/su and mRNA-1273 booster cohort will be stratified by age group (50 to 59 YOA, 60 
to 69 YOA, and ≥ 70 YOA) prior to randomization. Participants in the Flu D-QIV and 
mRNA-1273 booster cohort will also be stratified by age group (18 to 64 YOA and ≥ 65 
YOA) prior to randomization.  
The target will be to randomize approximately 546 eligible participants in the HZ/su and 
mRNA-1273 booster cohort, who would be randomly assigned to one of two study 
groups in a (1:1) ratio (approximately 273 participants in each group). The stratification 
by age will be set to ensure a minimum of 69 participants in the ≥ 70 YOA stratum in 
each group. 
The target will be to randomize approximately 1000 eligible participants in the Flu D-
QIV and mRNA-1273 booster cohort, who would be randomly assigned to 1 of 2 study 
groups in a (1:1) ratio (approximately 500 participants in each group). The stratification 
by age will be set to target  a minimum of 75 participants in the ≥ 65 YOA stratum in 
each group. 

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6.3.3. 
Intervention allocation to the participant 
Intervention (may be referred to as a treatment number or an intervention kit number) 
allocation for each participant will be performed through IRT at the first intervention 
visit. Once a participant ID is allocated, IRT will determine the study group and will 
provide the treatment number (kit number). The treatment number allocated to the 
participant will be recorded in IRT and treatment number actually administered will be 
recorded in the eCRF. As mRNA-1273 is presented in a multidose vial, the treatment 
number for a subsequent dose of mRNA-1273 to be administered to a different 
participant from the same vial, will be recorded in a custom table with the dose appended 
(e.g., treatment number/01, treatment number/02, treatment number/03, etc.). 
6.3.4. 
Blinding and unblinding 
Not applicable as this is an open-label study. Neither the participant nor the investigator 
can choose which group the participant will be allocated to. Once randomization has been 
completed, all involved parties will be aware of the participant’s group allocation. 
Codes will be used to link the participant and study to each sample to be tested in the 
laboratory. There will be no link between the study intervention groups and the identity 
of the participant. 
6.3.4.1. 
Emergency unblinding 
This is an open-label trial. Therefore, this section is not applicable.  
6.4. 
Study intervention compliance 
Participants will receive study intervention from the authorized study center staff. The 
date and site of administration of each study intervention dose in the clinic will be 
recorded in the source documents and in the eCRF. 
6.5. 
Dose modification 
Section is not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
There will be no continuing access to the study intervention after the end of the study.  
6.7. 
Treatment of overdose 
Any dose of any study vaccine greater than the one required per protocol is considered an 
overdose. All cases of vaccine overdose should be reported as protocol deviations. Any 
signs or symptoms resulting from an overdose should be reported as AEs, or SAEs if 
SAE criteria are met; overdose per se should not be reported as an AE/SAE. GSK does 
not recommend specific treatment for an overdose; however, any resulting adverse 
reaction should be treated symptomatically. 

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6.8. 
Concomitant therapy 
At each study visit/contact, the investigator or his/her delegate should question the 
participant about all medications/products/ taken, and vaccinations received by the 
participant. 
The following concomitant medication/product/vaccines must be recorded in the eCRF: 
• 
All concomitant medications ongoing at screening and any new concomitant 
medications administered after the first dose of study intervention until the end of the 
last unsolicited AE collection period. 
• 
All concomitant medication associated with an AE, including vaccines/products, 
administered after the first dose of study intervention. 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis (e.g., immunosuppressive or immune-modifying 
medications), including products/vaccines. 
• 
All concomitant medication which may explain/cause/be used to treat an 
SAE/AESI/pIMD including vaccines/products, as defined in Sections 8.3.1 and 
10.2.10. These must also be recorded in the Expedited Adverse Event report. 
The Medical Monitor (MM) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
The record of a concomitant therapy should include at a minimum the reason for use, 
dates of administration including start and end dates, dosage information including dose 
and frequency. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention 
may continue other study procedures (e.g. safety or immunogenicity), planned in the 
study protocol at the discretion of the investigator. 
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
AE requiring expedited reporting to PPD (see Section 10.2.12). 
• 
Unsolicited non-serious AE (see Section 10.2.4). 
• 
Solicited AE (see Section 10.2.3). 
• 
Not willing to be administered the study intervention. 
• 
Other (specify). 

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7.1.1. 
Contraindications to subsequent study intervention 
administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose. 
Participants who no longer meet any applicable eligibility criteria or meet any of the 
criteria listed below should not receive additional doses of study intervention. Such 
participants should be encouraged to continue other study procedures, at the 
investigator’s discretion (Section 10.2.10.1). All relevant criteria for discontinuation of 
study intervention administration must be recorded in the eCRF. 
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, including 
hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• 
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• 
Participants who develop any new condition that may impair their ability to adhere to 
required study procedures. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that in the 
opinion of the investigator, exposes the participant to unacceptable risk from 
subsequent vaccination. In such cases, the investigator should use his/her clinical 
judgement prior to administering the next dose of the study intervention. Refer to 
Section 10.2.5 for the definition of pIMD. 
• 
Occurrence of a new AESI or the exacerbation of an existing AESI that in the 
opinion of the investigator, exposes the participant to unacceptable risk from 
subsequent doses of study intervention. Refer to Section 10.2.6 for the definition of 
AESI. 
• 
Pregnancy. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who was not 
available for the concluding contact planned in the protocol. 
Investigators or designees will attempt to contact participants who do not return for 
scheduled visits or follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 

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The investigator will document whether the decision to withdraw a participant from the 
study was made by the participant himself/herself or by the investigator. The primary 
reason for study withdrawal will be documented in the eCRF, based on the list below: 
• 
AEs requiring expedited reporting to PPD (see Section 10.2.12). 
• 
Unsolicited non-serious AEs (see Section 10.2.4). 
• 
Solicited AE (see Section 10.2.3). 
• 
Withdrawal by participant, not due to an AE*. 
• 
Migrated/Moved from the study area. 
• 
Lost to follow-up (see Section 7.3). 
• 
Sponsor study termination. 
• 
Other (specify). 
*If a participant is withdrawn from the study because he/she has withdrawn consent and 
the reason for withdrawal was provided, the investigator must document this reason in the 
eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved or as described in Section 10.2.10.2. 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled 
visits and cannot be contacted by the study site. 
The following actions, unless specified differently in other study-related materials, must 
be taken if a participant fails to return to the clinic for a required study visit: 
• 
The study center must attempt to contact the participant and reschedule the missed 
visit as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Please refer to the Monitoring Plan for a description of actions to be taken before 
considering the participant lost to follow-up. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant. 
Immediate safety concerns should be discussed with the MM as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3). 
All screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria.  
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
Procedures conducted as part of routine clinical management (e.g. hematologic profiles), 
and obtained before the participant signed the ICF, may be used for screening and/or for 
establishing a clinical baseline (provided the procedure met protocol specified criteria 
and was performed within the time frame defined in the SoA [Section 1.3]) 
The study plans provide the investigator and site personnel with detailed administrative 
and technical information that does not impact participant safety. 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior IRB 
(or independent ethics committee) approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 

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8.1.1. 
Biological samples 
Refer to Table 10 for the schedule and details of sampling activities during this study. 
8.1.2. 
Laboratory assays 
Table 10 
Laboratory assays 
Assay Type 
System 
Component 
Method 
Laboratory 
Humoral 
Immunity 
(Antibody 
Determination) 
Serum 
Anti-glycoprotein E Ab.IgG 
ELISA 
GSK 
Anti-S Protein Ab* 
Multiplex 
Electrochemiluminescence assay** 
PPD 
SARS-CoV-2 NA 
Neutralization assay*** 
Nexelis 
A/Victoria/2570/2019 
Hemagglutination Inhibition 
Q2 
A/Tasmania/503/2020 
Q2 
B/Washington/02/2019 
Q2 
B/Phuket/3073/2013 
Q2 
Ab = antibody; ELISA = enzyme linked immunosorbent assay; NA = neutralizing antibody 
*Responses to other antigens (e.g., anti-N and anti-RBD proteins) may be generated in addition to anti-S Protein. 
**Other serological assays may be used to measure antibody responses 
***Assay to be conducted on the virus strain in the booster dose 
Table 11 
Molecular biology 
System 
Component 
Method 
Unit 
Laboratory 
HZ lesion sample 
Varicella Zoster Virus 
DNA 
PCR 
No unit 
GSK 
Actin Gene DNA 
PCR 
No unit 
GSK 
HZ = herpes zoster; DNA = deoxyribonucleic acid; PCR = polymerase chain reaction 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
Exploratory testing on the vaccines and/or on the disease under study may be performed 
within the framework of the study (i.e., exploratory objective) if deemed necessary for 
accurate interpretation of the data. These assays may or may not be represented in the 
objectives/endpoints of the study protocol. Pending final assay evaluations and 
validations prior to study sample testing, the multiplex electrochemiluminescence testing 
for assessing mRNA-1273 booster immune responses as the primary endpoint may be 
replaced with a neutralization assay to measure SARS-CoV-2 neutralizing antibody titers 
in all study participants, and if not, the assessment of neutralizing antibody titers will be 
restricted to a sub-cohort of approximately 50 participants. In addition, the exploratory 
assessment of anti-gE humoral immunogenicity at 1 month post-dose 1 of HZ/su may be 
limited, based upon the nature of the responses observed following the second dose of 
HZ/su and scientific relevance. 
GSK/ contract research organization’s (CRO) clinical laboratories have established a 
Quality System supported by procedures. The activities of GSK’s/ CRO’s clinical 
laboratories are audited regularly for quality assessment by an internal (sponsor-
dependent) but laboratory-independent Quality Department. Clinical laboratories 
contracted by GSK also conform to Good Laboratory Practice guidelines and operate in 
compliance with regulatory standards. 

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8.1.3. 
Immunological read-outs 
Table 12 
Immunological read-outs 
Study Group 
Number of 
participants 
Visit 1 
Day 1 
Visit 2 
Visit 3 
Visit 4 
Visit 6 
HZ/suSeq 
273 
SARS-CoV-2 Neutralizing Ab* 
Anti-S Protein IgG Ab** 
Anti-gE Ab 
SARS-CoV-2 Neutralizing Ab* 
Anti S Protein IgG Ab** 
Anti-gE Ab 
Anti-gE Ab 
HZ/suCoAd 
273 
SARS-CoV-2 Neutralizing Ab* 
Anti-S Protein IgG Ab** 
Anti-gE Ab 
SARS-CoV-2 Neutralizing Ab * 
Anti S Protein IgG Ab** 
Anti-gE Ab 
- 
Anti-gE Ab 
- 
FluD-QIVSeq 
500 
SARS-CoV-2 Neutralizing Ab* 
Anti-S Protein IgG Ab** 
HI Ab 
SARS-CoV-2 Neutralizing Ab* 
Anti S Protein IgG Ab** 
HI Ab 
- 
FluD-QIVCoAd 
500 
SARS-CoV-2 Neutralizing Ab* 
Anti-S Protein IgG Ab** 
HI Ab 
SARS-CoV-2 Neutralizing Ab* 
Anti S Protein IgG Ab** 
HI Ab 
- 
- 
- 
Ab = antibodies; IgG = immunoglobulin G 
*Samples may be tested on a sub-cohort (approximately 50 evaluable participants) post-hoc, based on other observed immune assay results or in all study participants if selected as a 
primary endpoint 
**Responses to other antigens (e.g., anti-N and anti-RBD proteins) may be generated in addition to anti-Spike Protein 
 

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8.1.4. 
Immunological correlates of protection 
No immunological correlate of protection against HZ or COVID-19 have yet been 
identified (see current IBs for Shingrix and mRNA-1273) (see the Glossary of terms for 
the definition of immunological correlate). 
Although no generally accepted immunological correlate of protection has been 
demonstrated so far against influenza (either seasonal or pandemic) with respect to 
specific levels of HI-specific antibody titer post-vaccination induced with inactivated 
influenza virus vaccines, the protective role of antibodies against haemagglutinin and, to 
a lesser extent, neuraminidase, is well established and has been demonstrated both in 
experimentally infected animals and humans [Brydak, 2000; Rimmelzwaan, 2008]. 
For this reason, the induction of HA-specific antibodies is used as a marker of potential 
vaccine efficacy and the serum HI assay is used to demonstrate this humoral response. 
Reciprocal HI antibody titers of 40 or greater have been associated with protection from 
influenza illness in at least 50% of adult subjects in some human challenge studies 
[Hannoun, 2004; Hobson, 1972]. 
8.2. 
Safety assessments 
The investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant’s withdrawal from the study 
intervention or study. 
Further details are provided in Section 10.2. 
8.2.1. 
Pre-intervention administration procedures 
8.2.1.1. 
Collection of demographic data 
Demographic data such as date of birth (year only), age, sex, race, and ethnicity will be 
collected from each participant and recorded. 
8.2.1.2. 
Medical/Vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the participant 
and/or review of the participant’s medical records. Record any pre-existing conditions, 
signs and/or symptoms present prior to the first dose of study intervention in the eCRF. 
Medical history should be collected, recorded, and verified that all inclusion and none of 
the exclusion criteria related to medical and vaccination history (Section 5.2) are met. 
Both axillae will be examined for lymph nodes (swelling/tenderness) and unless 
exclusionary, if present, will be documented as medical history. Skin overlying both 
deltoid muscles for evidence of any findings that may confound local solicited AE 
assessments (e.g., rashes or tattoos) will be assessed, and if present, the participant will 
be excluded. 

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8.2.1.3. 
History-directed physical examination 
History-directed physical examination will be performed. If the investigator determines 
that the participant’s health on the day of the study intervention administration 
temporarily precludes dosing, the visit will be rescheduled (see Section 5.5). 
8.2.1.4. 
Pregnancy test 
Female participants of childbearing potential must perform a urine pregnancy test on the 
day of and before the administration of any dose of study intervention. Pregnancy testing 
must be done even if the participant is menstruating at the time of the study visit. The 
study intervention may only be administered if the pregnancy test is negative. If a prior 
serum test result is necessary as per IRB requirement, unless the sample is obtained on 
the day of study intervention, then a urine test must also be performed on the day of and 
prior to study intervention administration. 
The urine pregnancy test kits (human chorionic gonadotropin [hCG] hormone test strip) 
provided to the study sites are approved by the FDA. Serum pregnancy testing, if 
required, will be performed as per standard of care. 
Refer to Section 10.3.3.1 for the information on study continuation for participants who 
become pregnant during the study. 
8.2.1.5. 
Warnings and precautions to administration of study intervention 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention. Refer to the approved 
product label/package insert for Shingrix and Fluarix Quadrivalent. 
8.2.2. 
Study holding rules and safety monitoring 
8.2.2.1. 
Safety review team oversight and staggered randomization 
An internal GSK safety review team (SRT) which may also include staff from Moderna, 
will oversee the safety of this study. Randomization will be temporarily paused after 10% 
and 5% of participants in the HZ/su and mRNA booster cohort and Flu D-QIV and 
mRNA booster cohort, respectively, have received the study vaccinations at Visit 1 and 
been followed up for 7-days post-vaccination. Safety data for 7 days post-dosing will be 
reviewed for the HZ/suCoAd and FluD-QIVCoAd groups by the SRT at this pre-
specified scheduled review. Randomization shall also be temporarily put on hold and an 
ad hoc SRT review will be performed if any of the holding rule criteria are met at any 
time during the study. Randomization can only be resumed following SRT approval to do 
so in the pre-specified scheduled or ad hoc SRT review. 
The SRT will also perform safety reviews after all participants in the HZ/su and mRNA-
1273 booster cohort sequential group have completed 14 days of follow-up after their 
HZ/su dose 1, and when all participants in the Flu D-QIV and mRNA-1273 cohort 
sequential group have completed 14 days of follow-up after their Flu D-QIV dose. 

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The SRT will also review all the safety data including solicited AEs, unsolicited AEs, 
SAEs, AESIs, IMCs, pIMDs, COVID-19 cases, pregnancies and suspected HZ cases at 
regular intervals during the conduct of the study while monitoring the safety holding 
rules (Section 8.2.2).  
Any potential safety concern related to conduct of the study will be managed as per 
internal GSK process. 
8.2.2.2. 
Study holding rules 
Study holding rules are defined in Table 13. These holding rules are applicable only for 
the co-administration groups (HZ/suCoAd and FluD-QIVCoAd). If any study team 
member from a site, PPD, or GSK identifies that a holding rule criterion may have been 
met, they must inform the PPD MM immediately (by calling the 24 hours safety hotline 
number; see section 8.3.3.1), who will notify the SRT, and if confirmed, PPD will place 
study randomization on hold until the SRT has been able to review all applicable safety 
data and provided a decision on whether to continue with randomizations and the study as 
planned or otherwise. Moreover, if the investigator becomes aware of a holding rule (e.g., 
1a or 1d) being met, he/she must suspend administration of the study intervention and 
inform the PPD MM immediately. Further details of SRT processes are provided in the 
SRT Charter. 
Table 13 
Study holding rules 
Holding 
Rule 
Event 
Number or Percentage of Participants 
For HZ/suCoAd group 
For FluD-QIVCoAd group 
1a 
Death or any life-threatening SAE that can be 
reasonably attributed to the vaccination 
1 participant 
1 participant 
1b 
Any non-life-threatening SAE that can be 
reasonably attributed to the vaccination 
3/28 participants (for 
initial SRT review); 
For the rest of the 
study: 10% 
3/25 participants (for initial 
SRT review); 
For the rest of the study: 
10% 
1c 
Any withdrawal from the study (by investigator 
or participant request) following a Grade 3 AE 
that can be reasonably attributed to the 
vaccination 
3/28 participants (for 
initial SRT review); 
For the rest of the 
study: 10% 
3/25 participants (for initial 
SRT review); 
For the rest of the study: 
10% 
1d 
Fever >40°C (104°F), OR 
Any solicited local event or solicited systemic 
AE leading to hospitalization, each within the 
7-day (Days 1-7) post-vaccination period 
2 participants 
2 participants 
2a 
Any Grade 3 solicited systemic AE (lasting 48h 
or more) within the 7-day (Day 1-7) post-
vaccination period 
6/28 participants (for 
initial SRT review); 
For the rest of the 
study: 20% 
5/25 participants (for initial 
SRT review); 
For the rest of the study: 
20% 
2b 
Any Grade 3 unsolicited AE, that can be 
reasonably attributed to the vaccination, within 
the 7-day (Day 1-7) post-vaccination period 
3/28 participants (for 
initial SRT review); 
For the rest of the 
study: 10% 
3/25 participants (for initial 
SRT review); 
For the rest of the study: 
10% 

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Risk assessment for study holding rules 
Figure 2 illustrates that, with 28 participants per study group in the HZ/su and mRNA-
1273 booster vaccine cohort at the pre-specified scheduled SRT review: 
• 
Each holding rule 1a and 1d has more than 75% chance of not being met for 
vaccination with a true incidence rate of 1% and has more than 95% chance of being 
met for vaccination with a true incidence rate above 10%. 
• 
Each holding rule 1b, 1c and 2b has more than 54% chance of not being met for 
vaccination with a true incidence rate below 10% and more than 81% chance of 
being met for vaccination with a true incidence rate above 15%. 
• 
Each holding rule 2a has more than 76% chance of not being met for vaccination 
with a true incidence rate below 15% and more than 50% chance of being met for 
vaccination with a true incidence rate above 20%. 
Figure 2 
Evaluations based on 28 participants in the co-administration group 
in HZ/su and mRNA-1273 booster cohort risk assessment curve 
based on the proposed safety holding rules 
 
Figure 3 illustrates that, with 25 participants per study group in the Flu D-QIV and 
mRNA-1273 booster vaccine cohort at the pre-specified scheduled SRT review: 
• 
Each holding rule 1a and 1d has more than 78% chance of not being met for 
vaccination with a true incidence rate of 1% and has more than 73% chance of being 
met for vaccination with a true incidence rate above 10%. 
• 
Each holding rule 1b, 1c and 2b has 54% chance of not being met for vaccination 
with a true incidence rate below 10% and has 75% chance of being met for 
vaccination with a true incidence rate above 15%. 

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• 
Each holding rule 2a has more than 68% chance of not being met for vaccination 
with a true incidence rate below 15% and more than 58% chance of being met for 
vaccination with a true incidence rate above 20%. 
Figure 3 
Evaluations based on 25 participants in the co-administration group 
in Flu D-QIV and mRNA-1273 booster cohort risk assessment curve 
based on the proposed safety holding rules 
 
8.3. 
Adverse events (AEs), serious adverse events (SAEs) and 
other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information 
The timeframes for collecting and reporting the safety information are provided in Table 
14. 
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Probability to conclude that a formulation is safe
True incidence rate
Holding rule 1b/1c/2b: At
least 3/25 subjects
Holding rule 2a: At least
5/25 subjects
Holding rule 1a: At least
1/25 subjects
Holding rule 1d: At least
2/25 subjects

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Table 14 
Timeframes for collecting and reporting of safety information 
EVENT 
TIMING OF REPORTING 
Local and systemic solicited events 
Day 1 through Day 7 following each study intervention administration (see Figure 1) 
Unsolicited AEs 
Day 1 through Day 30 following each study intervention administration (see Figure 1) 
AEs/SAEs leading to withdrawal from the study 
Day 1 following study intervention administration through Phone Contact 2 study conclusion 
All SAEs including SAEs related to the study intervention 
Day 1 following study intervention administration through Phone Contact 2 study conclusion 
AEs/SAEs related to study participation or SAEs related to 
concurrent GlaxoSmithKline medication/vaccine 
Enrollment (i.e., signing ICF) through Phone Contact 2 study conclusion 
IMCs, AESIs, COVID-19 cases, and in HZ/su and mRNA-1273 
booster cohort only, also pIMDs and suspected HZ episodes 
Day 1 following study intervention administration through Phone Contact 2 study conclusion 
Pregnancy 
Day 1 through Phone Contact 2 study conclusion 
 

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The investigator or designee will record and immediately report all 
SAEs/AESIs/pIMDs/pregnancies in study participants to PPD via the Expedited AE 
Reporting Form or pregnancy form (as applicable). Reporting should, under no 
circumstances, occur later than 24 hours after the investigator becomes aware of an 
SAE/AESI/pIMD/pregnancy, as indicated in Section 10.2.12. The investigator will 
submit any updated SAE/AESI/pIMD/pregnancy data to PPD within 24 hours of it being 
available. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 14. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. 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 a study intervention, the 
investigator will promptly notify the study contact for reporting SAEs mentioned in Table 
16. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events 
Detection and recording of AEs/SAEs/AESIs/pIMDs/pregnancies are detailed in 
Section 10.2.10. 
Assessment of AE/SAE/AESI/pIMD intensity, causality and outcome are described in 
Section 10.2.11. 
Open-ended and non-leading verbal questioning of participants is the preferred method of 
acquiring information related to an AE/SAE/AESI/pIMD/pregnancy. 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies and 
other events 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/AESI/pIMD/pregnancy, it must be reported to PPD using the 
required documentation and within the timeframes mentioned in Table 15. This is 
essential for meeting GSK and Moderna legal obligations and ethical responsibilities for 
participant safety and the safety of a study intervention under clinical investigation. 
For SAEs/AESIs/pIMDs, the investigator must always provide an assessment of causality 
at the time of the initial report, as defined in the Section 10.2.11.2. 
Local regulatory requirements, GSK and Moderna policy for preparation of an 
investigator safety report of Suspected Unexpected Serious Adverse Reactions (SUSAR) 
must be followed. These reports will be forwarded to investigators as necessary. 
GSK and Moderna have the legal responsibility to notify both local and other applicable 
authorities/regulatory agencies about the safety of an investigational study intervention 
under their IND. GSK and Moderna will comply with country-specific regulatory 
requirements related to safety reporting to the regulatory authority, IRB and investigators. 

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An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from PPD will review and 
then file it along with the IB and will notify the IRBs, if appropriate according to local 
requirements. 
Please refer to Section 10.2.12 for further details regarding the reporting of 
SAEs/AESIs/pIMDs/pregnancies. 
Table 15 
Timeframes for submitting SAE, AESI, pIMD, and pregnancy reports 
to PPD 
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited 
Adverse Events Report 
Pregnancies 
24 hours* 
electronic pregnancy report 
24 hours* 
electronic pregnancy report 
AESIs 
24 hours**  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited 
Adverse Events Report 
pIMDs 
24 hours**  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited 
Adverse Events Report 
*Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI or pIMD. 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, pIMDs, study holding 
rules and pregnancies  
Table 16 
Contact information for reporting SAEs, AESIs, pIMDs, study 
holding rules and pregnancies  
Study contact for questions regarding SAEs, AESIs, pIMDs, study holding rules, 
and pregnancies 
Refer to the local study contact information document 
Back up study contact for reporting SAEs, AESIs, pIMDs, study holding rules, 
and pregnancies 
Available 24/24 hours and 7/7 days: 
 
24 Hours Safety Hotline: 
+1 800 201 8725 
+1 910 558 7104 
24 Hour Safety Hotline Fax: 
+1 888 488 9697 
+1 919 654 3849 
8.3.4. 
Treatment of AEs 
Any medication administered for the treatment of an SAE/AESI/pIMD should be 
recorded in the Expedited Adverse Event Report of the participant’s eCRF screen (refer 
to Section 10.2.12.1). 

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8.3.5. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending 
physician/caregiver/family member that the participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator or his/her back-up. 
8.3.6. 
Medical device deficiencies 
One of the study interventions, the seasonal influenza vaccine, Flu D-QIV, is presented as 
a pre-filled syringe and according to the FDA regulations [FDA, 2018] is within scope of 
device reporting in clinical trials as a combination product constituted of a device and 
biologic product (e.g., pre-filled syringes). Refer to the Glossary of terms for the 
definition of the combination product and medical device deficiencies. Device-related 
incidents fulfilling the definition of an AE/SAE will also follow the processes outlined in 
Section 10.4. 
8.3.6.1. 
Detection, follow-up, and prompt reporting of medical device 
deficiency 
The investigator is responsible for the detection, documentation and prompt reporting of 
any medical device deficiency occurring during the study to PPD. This applies to any 
medical device provided for the conduct of the study. 
Device deficiencies will be reported to PPD within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. 
The investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or relatedness of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and also reported to PPD. 
Refer to Section 10.4 for definitions and details on recording and reporting of these 
events. 
8.3.6.2. 
Regulatory reporting of medical device deficiency when used as 
combination product 
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study to PPD. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to Section 10.4.3 for details of 
reporting. 

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The investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB. 
8.4. 
Pharmacokinetics 
Pharmacokinetics are not evaluated in this study. 
8.5. 
Genetics 
This section is not applicable. 
8.6. 
Biomarkers 
This section is not applicable. 
8.7. 
Immunogenicity assessments 
Immunogenicity is described in Section 8.1. 
8.8. 
Health outcomes 
This section is not applicable. 
8.9. 
Study procedures during special circumstances 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be followed. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
Safety follow-up may be made by a phone call, other means of virtual contact, or 
home visit, if appropriate. 
• 
The eDiary device may be returned to the study center by conventional mail after the 
end of the relevant data collection period. 
• 
Visits for suspected AEs may take place in a different location* other than the study 
center or at participant’s home. If this is not feasible, then the medical evaluation of 
AEs may take place remotely with documentation of symptoms by other means of 
communication (e.g., phone call or videoconference), if possible. 
• 
Biological samples may be collected at a different location* other than the study 
center or at participant’s home. Biological samples should not be collected if they 
cannot be processed in a timely manner or appropriately stored until the intended 
use. 

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*Note: It is the investigator’s responsibility to identify an alternate location. The 
investigator should ensure that this alternate location meets ICH Good Clinical 
Practice (GCP) requirements, such as adequate facilities to perform study 
procedures, appropriate training of the staff, and documented delegation of 
responsibilities in this location. This alternate location may need to be covered by 
proper insurance for the conduct of study on participants by investigator and study 
center staff other than the designated study center. 
The impact on PPS eligibility will be determined on a case-by-case basis. If despite best 
efforts, it is not possible to collect the biological samples within the interval pre-defined 
in the protocol, or if it is not possible to administer the second dose of HZ/su as defined 
in the protocol, then the interval may be extended. Details will be provided in the 
Statistical Analysis Plan.  
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
The study will test 4 hypotheses under the primary objectives and 1 hypothesis under a 
secondary immunogenicity objective. The objectives will be assessed independently for 
the two cohorts (HZ/su and mRNA-1273 booster, Flu D-QIV and mRNA-1273 booster) 
at the first interim analysis. All the safety analyses under the secondary objective are 
descriptive and are described in Section 9.3.6. 
Primary objectives for HZ/su and mRNA-1273 booster cohort: 
Hypothesis 1: The null hypothesis for this primary objective under consideration is 
Upper Limit (UL) of 95% CI for adjusted GMC ratio between HZ/suSeq group and 
HZ/suCoAd group for anti-gE antibody concentration at 1 month post-dose 2 of HZ/su 
(at Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd) is ≥1.5. 
Success criteria: The objective will be met if the UL of the 95% CI of the adjusted GMC 
ratio between HZ/suSeq and HZ/suCoAd group for anti-gE antibody concentration at 1 
month post-dose 2 of HZ/su (at Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd) is 
<1.5. 
Hypothesis 2: The null hypothesis for this primary objective under consideration is UL of 
95% CI for adjusted GMC ratio between HZ/suSeq and HZ/suCoAd group for anti-S 
protein antibody concentration at 1 month post mRNA-1273 booster dose (at Week 4 for 
HZ/suSeq and HZ/suCoAd) is ≥ 1.5. 
Success criteria: The objective will be met if the UL of the 95% CI of the adjusted GMC 
ratio between HZ/suSeq and HZ/suCoAd group for anti-S protein antibody at 1 month 
post mRNA-1273 booster dose (at Week 4 for HZ/suSeq and HZ/suCoAd) is <1.5. 
Primary objectives for Flu D-QIV and mRNA-1273 booster cohort: 
Hypothesis 3:- The null hypothesis for this primary objective under consideration is UL 
of 95% CI for adjusted GMT ratio between FluD-QIVSeq and FluD-QIVCoAd group for 
anti-HI antibody titer at 1 month post Flu D-QIV (at Week 6 for FluD-QIVSeq, at Week 
4 for FluD-QIVCoAd) is ≥ 1.5. 

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Success criteria - The objective will be met if the UL of the 95% CI of the adjusted GMT 
ratio between FluD-QIVSeq and FluD-QIVCoAd group for anti-HI antibody titer at 1 
month post Flu D-QIV (at Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd) is 
<1.5 for each strain included in the Flu D-QIV vaccine.  
Hypothesis 4: The null hypothesis for this primary objective under consideration is UL of 
95% CI for adjusted GMC ratio between FluD-QIVSeq and FluD-QIVCoAd group for 
anti-S protein antibody concentration at 1 month post mRNA-1273 booster dose (at 
Week 4 for FluD-QIVSeq and FluD-QIVCoAd) is ≥ 1.5. 
Success criteria - The objective will be met if the UL of the 95% CI of the adjusted GMC 
ratio between FluD-QIVSeq and FluD-QIVCoAd group for anti-S protein antibody 
concentration at 1 month post mRNA-1273 booster dose (at Week 4 for FluD-QIVSeq 
and FluD-QIVCoAd) is <1.5. 
Secondary objective for Flu D-QIV and mRNA-1273 booster cohort: 
The secondary objective for the Flu D-QIV and mRNA-1273 booster cohort will be 
assessed once the primary objective for Flu D-QIV and mRNA-1273 booster cohort is 
demonstrated. This will not be used to confirm study success, rather, for informative 
purposes to support the primary endpoint. 
Hypothesis 5: The null hypothesis for this secondary objective under consideration is UL 
of the 95% CI of the SCR difference between FluD-QIVSeq and FluD-QIVCoAd group 
at 1 month post Flu D-QIV (at Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd) 
is ≥ 10%. 
Success criteria: The objective will be met if the UL of the 95% CI of the SCR difference 
between FluD-QIVSeq and FluD-QIVCoAd group at 1 month post Flu D-QIV (at 
Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd) is <10% for each strain 
included in the Flu D-QIV vaccine.  
9.2. 
Analysis sets 
The analysis sets defined in this study are provided in Table 17. As separate analysis 
presentations will be provided for the HZ/su and mRNA-1273 booster cohort and the Flu 
D-QIV and mRNA-1273 booster cohort, separate analysis sets are defined for each 
cohort. 
In the HZ/su and mRNA-1273 booster cohort, the HZ/su and mRNA-1273 PPS will be 
used for analysis of hypothesis 1 and hypothesis 2. In the Flu D-QIV and mRNA-1273 
booster cohort, the Flu D-QIV and mRNA-1273 PPS will be used for analysis of 
hypothesis 3, hypothesis 4, and hypothesis 5. 
If, in any vaccine group, the percentage of vaccinated participants with serological results 
excluded from either PPS is 5% or more, a second analysis based on the HZ/su and 
mRNA-1273 Exposed set or Flu D-QIV and mRNA-1273 Exposed set will be performed 
to complement the Per-Protocol analysis. 

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Table 17 
Analysis sets 
Analysis set 
Description 
Enrolled Set 
The enrolled set will include all participants who sign the informed consent. 
Randomized set 
The randomized set will include all participants from the enrolled set who are 
randomized. 
HZ/su and mRNA-1273 Exposed 
Set 
The HZ/su and mRNA-1273 Exposed set will include all participants in the 
HZ/su and mRNA-1273 booster cohort with at least 1 vaccine administration. 
The Exposed set analysis will be performed per vaccine(s) actually 
administered (at Day 1). 
The HZ/su and mRNA-1273 Exposed set for analysis of immunogenicity will 
include vaccinated participants for whom immunogenicity data are available. 
HZ/su and mRNA-1273 PPS (For 
Hz/su and mRNA-1273 booster 
cohort) 
 
The HZ/su and mRNA-1273 PPS will include all participants from the HZ/su 
and mRNA-1273 Exposed set  
Who meet all eligibility criteria; 
Who receive all doses of study interventions according to their random 
assignment; 
For whom administration site of study vaccine is known; 
Who do not receive any other prohibited concomitant medication/vaccine up to 
blood sample post HZ/su dose 2. 
Who comply with the procedures and intervals defined in the protocol and 
allowed for analysis up to blood sample post HZ/su dose 2; 
Who do not meet any of the criteria for elimination up to blood sample post 
HZ/su dose 2;  
For whom data concerning immunogenicity endpoint measures are available 
at post vaccination for either mRNA-1273 booster or HZ/su dose 2. 
Flu D-QIV and mRNA-1273 
Exposed Set (For Flu D-QIV and 
mRNA-1273 booster cohort) 
The Flu D-QIV and mRNA-1273 Exposed set will include all participants in the 
Flu D-QIV and mRNA-1273 booster cohort with at least 1 vaccine 
administration documented. The Exposed set analysis will be performed per 
vaccine(s) actually administered (at Day 1). 
The Flu D-QIV and mRNA-1273 Exposed set for analysis of immunogenicity 
will include vaccinated participants for whom immunogenicity data are 
available. 
Flu D-QIV and mRNA-1273 PPS  
(For Flu D-QIV and mRNA-1273 
booster cohort) 
The Flu D-QIV and mRNA-1273 PPS will include all participants from the Flu 
D-QIV and mRNA-1273 Exposed set  
Who meet all eligibility criteria; 
Who receive all doses of study interventions according to their random 
assignment; 
For whom administration site of study vaccine is known; 
Who do not receive any other prohibited concomitant medication/vaccine. 
Who comply with the procedures and intervals defined in the protocol and 
allowed for analysis; 
Who do not meet any of the criteria for elimination during the study through the 
last blood sample for the group; 
For whom data concerning immunogenicity endpoint measures are available 
at post vaccination for either mRNA-1273 booster or Flu D-QIV. 
9.2.1. 
Criteria for elimination from analysis 
Participants may be eliminated from the PPS in their respective cohort, if, during the 
study up to blood sampling timepoint post last dose, they incur a condition that has the 
capability of altering their immune response (i.e., an IMC) or are confirmed to have an 
alteration of their initial immune status. Refer to Glossary of terms for the definition of 
intercurrent medical conditions. More details on other reasons for elimination will be 
presented in the SAP. 

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9.3. 
Statistical analyses 
9.3.1. 
Statistical analysis plan 
The SAP will be developed and finalized before First Participant First Visit (FPFV) and 
will describe the participant analysis sets to be included in the analyses and procedures 
for accounting for missing, unused, and spurious data.  
This section is a summary of the planned statistical analyses of the primary and 
secondary endpoints.  
Unless otherwise mentioned, for all the planned analyses with CI, a 95% CI will be 
computed. 
9.3.2. 
General considerations 
During special circumstances (e.g., the COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare will be followed. For the duration of such special circumstances, 
some measures may impact the data and analysis (e.g., missing visits, early study 
discontinuation). The impact will be determined on a case by case basis and the analysis 
methodology described in the SAP will account for such cases, if any. 
9.3.3. 
Participants disposition 
Number of screened, enrolled, exposed (at least 1 study intervention, full study 
intervention course), and eligible for the PPS included in each cohort, group and overall 
will be described. 
9.3.4. 
Primary endpoints analysis 
The primary endpoints related to immunogenicity analysis are described in Section 3, 
Objectives and Endpoints.  
Differing analysis sets (refer to Section 9.2) will apply to each primary endpoint.  
9.3.4.1. 
Primary endpoints for HZ/su and mRNA1273 booster study cohort 
9.3.4.1.1. HZ/su immunogenicity post-dose 2 (anti-gE antibodies) 
The immunogenicity assessment of the HZ/su primary endpoint (Hypothesis 1 stated in 
Section 9.1) will be summarized on the HZ/su and mRNA-1273 PPS. 
Anti-gE antibody concentrations will be expressed as a between-group GMC ratio at 1 
month post-dose 2 of HZ/su (at Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd) and 
will be summarized.  

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For anti-gE at 1 month post-dose 2 of HZ/su, the 95% CI of the between-group GMC 
ratios will be computed using an analysis of covariance (ANCOVA) model on the log10 
transformation of the concentrations. The age strata (50-59, 60-69, ≥70 YOA) and 
pre-vaccination log-transformed antibody concentrations will be included as covariates 
and vaccine group will be included as a fixed effect. 
9.3.4.1.2. mRNA-1273 booster immunogenicity (anti-S protein antibodies) 
The immunogenicity assessment of the mRNA-1273 booster primary endpoint 
(Hypothesis 2 stated in Section 9.1) will be summarized on the HZ/su and mRNA-1273 
PPS  
Anti-S Protein antibody concentrations will be expressed as a between-group GMC ratio 
at 1 month post mRNA-1273 booster dose (at Week 4 for both groups, HZ/suSeq and 
HZ/suCoAd).  
For anti-S Protein at 1 month post mRNA-1273 booster dose, the 95% CI of the between-
group GMC ratios will be computed using an analysis of covariance (ANCOVA) model 
on the log10 transformation of the concentrations. The age strata (50-59, 60-69, ≥70 
YOA) and pre-vaccination log-transformed antibody concentrations will be included as 
covariates and vaccine group will be included as a fixed effect. 
Pending final assay evaluations and validations prior to study specimen testing, anti-S 
protein may be replaced with SARS-CoV-2 neutralizing antibody titers in which case, 
GMT ratios will be used in the analysis described above. 
9.3.4.2. 
Primary endpoints for Flu D-QIV and mRNA-1273 booster study cohort 
9.3.4.2.1. Flu D-QIV immunogenicity (anti-HI antibodies) 
The immunogenicity assessment of the Flu D-QIV primary endpoint (Hypothesis 3 stated 
in Section 9.1) will be summarized on the Flu D-QIV and mRNA-1273 PPS. 
Anti-HI antibody titers against the 4 influenza strains included in Flu D-QIV will be 
expressed as a between-group GMT ratio at 1 month post Flu D-QIV (at Week 6 for 
FluD-QIVSeq, at Week 4 for FluD-QIVCoAd).  
To demonstrate non-inferiority of Flu D-QIV in terms of anti-HI antibody GMTs, the 
95% CI of the between-group GMT ratios post-dose 1 of Flu D-QIV will be computed 
using an ANCOVA model on the log10 transformation of the titers. The pre-vaccination 
log-transformed antibody titers and age strata (18-64, ≥65 YOA) will be included as 
covariates and vaccine group will be included as a fixed effect. This will be done for each 
of the 4 strains included in the Flu D-QIV vaccine. 
9.3.4.2.2. mRNA-1273 booster immunogenicity (anti-S protein antibodies) 
The immunogenicity assessment of the mRNA-1273 primary endpoint (Hypothesis 4 
stated in Section 9.1) will be summarized for the Flu D-QIV and mRNA-1273 PPS  

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Anti-S Protein antibody concentrations will be expressed as a between-group GMC ratio 
at 1 month post mRNA-1273 booster dose (at Week 4 for FluD-QIVSeq and 
FluD-QIVCoAd).  
For anti-S Protein at 1 month post mRNA-1273 booster dose, the 95% CI of the between-
group GMC ratios will be computed using an analysis of covariance (ANCOVA) model 
on the log10 transformation of the concentrations. The pre-vaccination log-transformed 
antibody concentrations and age strata (18-64, ≥65 YOA) will be included as covariates 
and vaccine group will be included as a fixed effect.  
9.3.5. 
Secondary immunogenicity endpoints analyses 
9.3.5.1. 
Flu D-QIV immunogenicity (Anti-HI antibody SCRs) 
The immunogenicity assessment of the Flu D-QIV secondary endpoint (Hypothesis 5 
stated in Section 9.1) will be summarized for the Flu QIV and mRNA-1273 PPS 
Anti-HI antibody SCRs against the 4 influenza strains will be summarized by group 
(FluD-QIVSeq and FluD-QIVCoAd).  
To demonstrate non-inferiority of Flu D-QIV in terms of HI antibody SCRs for each 
strain, the difference between the SCR and the 95% CI for the difference in SCR in the 
FluD-QIVSeq group as compared to the FluD-QIVCoAd group at 1 month post Flu D-
QIV (at Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd) will be evaluated.  
The 2-sided 95% confidence interval (CI) on group difference in seroconversion rate will 
be computed based on the method of Miettinen and Nurminen [Miettinen, 1985]. 
9.3.5.2. 
Descriptive immune endpoints 
9.3.5.2.1. Anti-gE humoral immunogenicity at pre-vaccination and post-dose 2 of 
HZ/su 
Descriptive statistics (including 95% CIs) of the following anti-gE humoral 
immunogenicity parameters will be provided by group and by age category (50-59, 60-
69, ≥ 70 YOA). Analyses at 1 month post-dose 2 of HZ/su will use the HZ/su and 
mRNA-1273 PPS. 
• 
VRR with exact 95% CI at 1 month post-dose 2 of HZ/su (at Week 14 for HZ/suSeq, 
at Week 12 for HZ/suCoAd)  
− 
The VRR for anti-gE post-dose 2 is defined as the percentage of participants 
who have at least: 
o 
A 4-fold increase in the post-dose anti-gE antibodies concentration as 
compared to the pre-vaccination anti-gE antibodies concentration, for 
participants who are seropositive at pre-vaccination, or, 

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o 
A 4-fold increase in the post-dose anti-gE antibodies concentrations as 
compared to the anti-gE antibodies cut-off value for seropositivity, for 
participants who are seronegative at pre-vaccination. 
This will be summarized by participants who are seronegative at pre-vaccination, 
seropositive at pre-vaccination and overall status at pre-vaccination (seronegative or 
seropositive) 
• 
Seropositivity rate with exact 95% CI at pre-vaccination (at Day 1 for HZ/suCoAd, 
at Week 2 for HZ/suSeq) and at 1 month post-dose 2 of HZ/su (at Week 14 for 
HZ/suSeq, at Week 12 for HZ/suCoAd). Seropositivity is defined as the percentage 
of participants whose antibody concentration is greater than or equal to the assay cut-
off value (97 mIU/mL). 
• 
Anti-gE antibody concentrations expressed as GMC with 95% CI at pre-vaccination 
(at Day 1 for HZ/suCoAd, at Week 2 for HZ/suSeq) and at 1 month post-dose 2 of 
HZ/su (at Week 14 for HZ/suSeq, at Week 12 for HZ/suCoAd). GMC calculations 
will be performed by taking the anti-log of the mean of the log concentration 
transformations. Anti-gE antibody concentrations will be displayed using reverse 
cumulative curves.  
• 
MGI from pre-vaccination with 95% CI at 1 month post-dose 2 of HZ/su (at Week 
14 for HZ/suSeq, at Week 12 for HZ/suCoAd). 
• 
Descriptive statistics of fold increase from baseline for anti-gE antibody ELISA 
concentrations 
• 
The distribution of the fold increase i.e. percentage of participants with a more than 
X-fold (e.g. >2, >4, >6,...-fold) increase along with 95% CI will be presented. 
9.3.5.2.2. mRNA-1273 booster dose humoral immunogenicity  
Descriptive statistics (including 95% CIs) of the following mRNA-1273 booster 
immunogenicity parameters will be provided by group and by age category (50-59, 60-
69, ≥ 70 YOA for HZ/su and mRNA-1273 booster cohort, 18-64, ≥ 65 YOA for Flu D-
QIV and mRNA-1273 booster cohort). All summaries will be provided for the HZ/su and 
mRNA-1273 PPS and for the Flu D-QIV and mRNA-1273 PPS in the respective cohorts. 
• 
Anti-S Protein antibody concentrations expressed as GMC with 95% CIs by group at 
pre-vaccination (Day 1) and 1 month post mRNA-1273 booster dose (at Week 4 for 
all groups including HZ/suSeq, HZ/suCoAd, FluD-QIVSeq, FluD-QIVCoAd and 
overall). The GMC calculations will be performed by taking the anti-log of the mean 
of the log concentration transformations. Anti-S protein antibody concentrations will 
be displayed using reverse cumulative curves. 
• 
MGI with 95% CI at 1 month post mRNA-1273 booster dose (at Week 4 for all 
groups). 
Pending final assay evaluations and validations prior to study specimen testing, anti-S 
protein may be replaced with SARS-CoV-2 neutralizing antibody titers in which case, 
GMTs will be used in the analysis described above. 

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9.3.5.2.3. Flu D-QIV humoral immunogenicity 
Descriptive statistics, including 95% CIs, will be produced for the following Flu D-QIV 
humoral immunogenicity parameters for each of the 4 influenza vaccine strains by group 
and age categories (18-64, ≥ 65 YOA). Summaries will be produced for the Flu D-QIV 
and mRNA-1273 PPS. 
• 
Anti-HI antibody titers against the 4 influenza strains included in Flu D-QIV 
expressed as GMTs with 95% CIs at pre-vaccination and at 1 month post Flu D-QIV 
(at Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). GMT calculations 
will be performed by taking the anti-log of the mean of the log titer transformations. 
Anti-HI antibody titers will be displayed using reverse cumulative curves. 
SPR with exact 95% CIs at pre-vaccination and at 1 month post Flu D-QIV (at Week 
6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). SPR is defined as the 
percentage of participants with a serum HI titer ≥ 1:40. 
• 
Seropositivity rates with exact 95% CIs at pre-vaccination and at 1 month post Flu 
D-QIV (at Week 6 for FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). 
• 
MGI from pre-vaccination with 95% CIs at 1 month post Flu D-QIV (at Week 6 for 
FluD-QIVSeq, at Week 4 for FluD-QIVCoAd). MGI is defined as the geometric 
mean of the within participant ratios of the post-vaccination reciprocal HI titer to the 
Day 1 reciprocal HI titer. 
• 
SCR with exact 95% CIs at 1 month post Flu D-QIV (at Week 6 for FluD-QIVSeq, 
at Week4 for FluD-QIVCoAd). SCR is defined as the percentage of participants who 
have either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-
vaccination titer ≥ 1:10 and at least a 4 fold increase in post-vaccination titer.  
The assessment of SPR and SCR will also be performed by age categories (18-64, ≥65 
YOA) descriptively based on the following CBER criteria: 
• 
The lower limit of the 95% confidence interval for SPR should be ≥ 70% in 
participants aged 18-64 YOA or ≥ 60% in participants ≥ 65 YOA. 
• 
The lower limit of the 95% confidence interval for SCR should be ≥ 40% in 
participants aged 18-64 YOA or ≥ 30% in participants ≥ 65 YOA. 
At least one of the 4 strains must meet the criteria above for SPR and SCR to be 
considered as having met CBER criteria. 
9.3.6. 
Secondary endpoints analyses 
The safety endpoints will be summarized on the HZ/su and mRNA-1273 Exposed set and 
on the Flu D-QIV and mRNA-1273 Exposed Set. The analyses will be descriptive. 
Subgroup analyses may be performed and will be detailed in the statistical analysis plan 
(SAP). 

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9.3.6.1. 
Solicited local and systemic AEs 
The percentage of participants with at least 1 solicited local event, with at least 1 solicited 
systemic event and any solicited event during the 7-day follow-up period will be 
tabulated, for each vaccination visit and overall, with exact 95% CIs. Similar summaries 
will be provided for Grade 3 events 
The number and percentage of participants reporting each solicited local and solicited 
systemic AE during the solicited 7-day follow-up period will be tabulated with exact 95% 
CIs after each vaccination visit and overall per participant for all study groups 
(HZ/suSeq, HZ/suCoAd, FluD-QIVSeq, FluD-QIVCoAd and overall). 
• 
Solicited local events (intensity [any grade, Grade 3], resulting in medically attended 
visit) during the 7-day follow-up period after each intervention administration will be 
summarized. Any events ongoing beyond the 7-day post-vaccination period, 
following each vaccination visit and overall will also be tabulated for each vaccine 
separately. 
• 
Solicited systemic events (intensity [any grade, Grade 3], and resulting in a 
medically attended visit) during the 7-day follow-up period after each vaccination 
visit will be summarized. Any events ongoing beyond the 7-day post-vaccination 
period, following each vaccination visit and overall will also be tabulated for each 
vaccine separately. 
• 
The duration of the solicited AEs, both local (for each vaccine separately) and 
systemic, during the 7-day follow-up period after each vaccination visit and overall 
(total duration) will be calculated and summarized by mean, median, standard 
deviation, and range. 
9.3.6.2. 
Unsolicited AEs 
The number and percentage of participants reporting unsolicited AEs classified by 
MedDRA primary System Organ Class (SOC) and Preferred Term (PT) will be 
summarized along with exact 95% CIs during: 
• 
The 14-day post-vaccination period after each and any vaccination visit for all study 
groups and 
• 
The 30-day post-vaccination period after each and any vaccination visit. It should be 
noted that participants in the HZ/suSeq and FluD-QIVSeq groups will receive their 
HZ/su or Flu D-QIV, respectively, at Day 14 post mRNA booster vaccine dose at 
Day 1. 
Unsolicited AEs will also be presented by intensity (any grade and Grade 3), any related, 
Grade 3 related, Grade 3 non-serious, Grade 3 non-serious related, and resulting in a 
medically-attended visit. 
9.3.6.3. 
SAEs 
Number and percentage of participants reporting SAEs and fatal SAEs from first 
vaccination up to 30 days post-last vaccination and from first vaccination up to study end 

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will be summarized for all study groups (HZ/suSeq, HZ/suCoAd, FluD-QIVSeq, FluD-
QIVCoAd and overall). Any related SAEs will also be presented for all study groups 
(HZ/suSeq, HZ/suCoAd, FluD-QIVSeq, FluD-QIVCoAd and overall). Fatal SAEs will 
be presented by onset day and day of death, for both any fatal SAEs and any related fatal 
SAEs. All SAEs will be summarized by MedDRA SOC and PT. SAEs, fatal SAEs and 
withdrawals due to SAEs will also be listed. 
9.3.6.4. 
Potential Immune-mediated Diseases (for HZ/su and mRNA-1273 
booster cohort only) 
Number and percentage of participants reporting pIMDs from first vaccination up to 30 
days post-last vaccination and from first vaccination up to study end will be summarized 
for all study groups (HZ/suSeq, HZ/suCoAd, overall). All pIMDs will be summarized by 
MedDRA SOC and PT. pIMDs will also be listed. Any related pIMD will also be 
presented for study groups (HZ/suSeq, HZ/suCoAd and overall). 
9.3.6.5. 
Adverse events of special interest 
Number and percentage of participants reporting AESIs from first vaccination up to 30 
days post-last vaccination and from first vaccination up to study end will be summarized 
for all study groups. All AESIs will be summarized by MedDRA SOC and PT. A listing 
of AESIs will also be presented. 
9.3.6.6. 
Suspected HZ episodes (for HZ/su and mRNA-1273 booster cohort 
only) 
Number and percentage of participants reporting suspected HZ episodes from first dose 
to study end will be summarized for the HZ/suSeq and HZ/suCoAd study groups and 
overall. Potential HZ episodes throughout the entire study period will be listed by 
MedDRA PT. 
9.3.6.7. 
COVID-19 cases 
Number and percentage of participants meeting the case definitions of COVID-19 from 
first dose to study end will be summarized for all study groups (HZ/suSeq, HZ/suCoAd, 
FluD-QIVSeq, FluD-QIVCoAd and overall) and COVID-19 cases will also be listed. 
9.3.6.8. 
Pregnancies 
A listing of participants with confirmed pregnancies from first dose to study end will be 
provided for all study groups along with pregnancy details. 
9.3.6.9. 
Withdrawals due to AEs and SAEs 
Withdrawals due to solicited AEs, both local and systemic, unsolicited AEs, and SAEs 
will be presented in a listing. 

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9.3.7. 
Exploratory endpoints analyses 
Anti-gE humoral immunogenicity at post-dose 1 of HZ/su: 
Anti-gE antibody testing post-dose 1 may be limited, based upon the nature of the 
responses observed following the second dose of HZ/su and scientific relevance. Similar 
descriptive statistics will be presented for these results at 1 month post-dose 1 of HZ/su 
as described in Section 9.3.5.2.1. 
Confirmed HZ cases (for HZ/su and mRNA-1273 booster cohort only): 
• 
Number and percentage of participants reporting clinically confirmed HZ cases by 
PCR from first vaccination up to study end will be summarized for all study groups 
(HZ/suSeq, HZ/suCoAd, and overall). 
Neutralizing antibodies (assuming if not assessed as a primary endpoint in all 
participants): 
• 
GMT with 95% CI of SARS-CoV-2 neutralizing antibody concentrations in a sub-
cohort of participants in each study group (HZ/suSeq, HZ/suCoAd, FluD-QIVSeq, 
FluD-QIVCoAd and overall) at pre-vaccination and 1 month post mRNA-1273 
booster (at Week 4 for all groups). The sub-cohort (approximately 50 evaluable 
participants) will be selected post-hoc, based on other observed immune assay 
results. 
Descriptive humoral immune responses to vaccination and/or SARS-CoV-2 infection: 
• 
GMCs with 95% CI of anti-RBD protein antibodies at pre-vaccination and at 1 
month post mRNA-1273 booster (at Week 4 for all study groups [HZ/suSeq, 
HZ/suCoAd, FluD-QIVSeq, FluD-QIVCoAd and overall]). 
Descriptive humoral immune responses to SARS-CoV-2 infection: 
• 
Anti-N seroconversion rate with exact 95% CI from pre-vaccination to 1 month post 
mRNA-1273 booster dose (at Week 4 for all study groups). Seroconversion is 
defined as a participant who is seronegative at baseline and seropositive post-
vaccination OR for a participant seropositive at baseline, a 4-fold or more increase 
post-vaccination. 
9.3.8. 
Other analyses 
9.3.8.1. 
Demography and baseline characteristics analyses 
For the HZ/su and mRNA-1273 booster study cohort, summaries of demographic 
characteristics will be produced for the HZ/su and mRNA-1273 Exposed Set and HZ/su 
and mRNA-1273 PPS by study group (HZ/suSeq and HZ/suCoAd and overall [i.e. both 
HZ/su groups]).  
For the Flu D-QIV and mRNA-1273 booster study cohort, summaries of demographic 
characteristics will be produced for the Flu D-QIV and mRNA-1273 Exposed Set and Flu 
D-QIV and mRNA-1273 PPS by study group (FluD-QIVSeq, FluD-QIVCoAd and 
overall [i.e. both Flu D-QIV groups]). 

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Demographic characteristics (age at intervention in years, age category [50-59, 60-69, 
≥70YOA for HZ/su and mRNA-1273 booster cohort; 18-64, ≥65 YOA for Flu D-QIV 
and mRNA-1273 booster cohort] sex, and race and ethnicity) will be summarized by 
group using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as race. 
• 
Mean, median, standard error, and range will be provided for continuous data such as 
age. 
Withdrawal status will be summarized by study group using descriptive statistics for the 
HZ/su and mRNA-1273 Exposed Set and Flu D-QIV and mRNA-1273 Exposed Set only: 
• 
The number of participants enrolled into the trial as well as the number of 
participants excluded from per-protocol analyses will be tabulated along with 
reasons for elimination. A listing of protocol deviations will be provided. 
• 
CONSORT tables will be generated to show the dispositions of participants from the 
enrolled set to the exposed sets and from the exposed sets to the per protocol sets. 
• 
The numbers of withdrawn participants will be tabulated according to the reason for 
withdrawal. 
The percentage of participants using a concomitant medication/vaccination during the 7-
day follow-up period and during the 30-day follow-up period after each intervention 
administration will be summarized.  
9.4. 
Interim analyses 
9.4.1. 
Sequence of analyses 
The SRT will first review safety and reactogenicity data reported up to 7 days post-dose 1 
of HZ/su when 10% of participants in the HZ/suCoAd group and 7 days post Flu D-QIV 
when 5% of participants in the FluD-QIVCoAd group have been vaccinated. Selected 
tabulations will be generated for SRT review to decide on continuation of enrollment in 
the co-administration groups. Limited safety analyses will be performed after all 
participants in the HZ/su and mRNA-1273 booster cohort sequential group have 
completed 14 days of follow-up after their HZ/su dose 1, and when all participants in the 
Flu D-QIV and mRNA-1273 cohort sequential group have completed 14 days of follow-
up after their Flu D-QIV dose. Periodic analyses will be done for regular SRT review. All 
SRT analyses will be descriptive. 
In addition to the SRT review, 1 formal interim analysis of safety, reactogenicity, and 
immunogenicity is planned. 
9.4.2. 
First interim analysis 
The first interim analysis will include analysis of safety, reactogenicity, and 
immunogenicity when the last participant enrolled in the HZ/su and mRNA-1273 booster 
cohort completes 6 weeks post-dose 2 of HZ/su Phone Contact 1. These participants will 

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also have completed the 4 weeks of follow-up post mRNA-1273 booster vaccine visit. 
Participants in the Flu D-QIV cohort will have also completed 4 weeks of follow-up post 
Flu D-QIV and post mRNA-1273 booster vaccine at this stage. 
Analysis will be performed on data as clean as possible and clinical study report will be 
provided. Individual participant listings will be provided at this stage. 
The first interim analysis will include: 
• 
The assessment of non-inferiority of the humoral immune response to Dose 2 of 
HZ/su (HZ/suSeq and HZ/suCoAd groups). 
• 
The assessment of non-inferiority of the humoral immune response to Flu D-QIV 
(FluD-QIVSeq and FluD-QIVCoAd groups). 
• 
The assessment of non-inferiority of the humoral immune response to mRNA-1273 
booster dose (both cohorts [HZ/su, Flu D-QIV], all groups [HZ/suSeq, HZ/suCoAd, 
FluD-QIVSeq, FluD-QIVCoAd]) (when co-administered with HZ/su and when co-
administered with Flu D-QIV). 
• 
Reactogenicity data after each administered vaccine dose (All groups: All doses of 
Flu D-QIV and mRNA-1273 booster dose; and all doses of HZ/su). 
• 
Unsolicited AEs (serious and non-serious) safety data will also be included up to 30 
days follow-up post each dose (All groups; including post all doses of Flu D-QIV 
and mRNA-1273 booster dose; and post all doses of HZ/su). 
• 
SAEs, pIMDs, AESIs, suspected HZ episodes, IMCs, COVID-19 cases and 
pregnancies until the Data Lock Point (DLP) for all groups. 
9.4.3. 
Final analysis 
The final analysis will include safety follow-up up to 6 months post the last vaccine 
dose. At that time, an integrated study report will be written. Individual participant 
listings will be available at this stage. 
9.4.4. 
Statistical considerations for interim analysis 
Refer to Section 9.1 for details on type I error adjustments. 
Hypothesis testing at the first interim analysis will occur in parallel within each cohort. 
The assessment of success for the confirmatory immunogenicity objective in the HZ/su 
and mRNA-1273 booster cohort will be made at the first interim analysis. Similarly, the 
determination of success for the confirmatory immunogenicity objective for the Flu D-
QIV and mRNA-1273 booster cohort will be made at the first interim analysis. 
9.5. 
Sample size determination 
Assumptions used for the sample size calculations come from data available from prior 
studies ZOSTER-004 (117036), ZOSTER-042 (116887), ZOSTER-035 (116889), 
ZOSTER-048 (201198), ZOSTER-059 (204487), FLU D-QIV-008 (114269), FLU D-
QIV-010 PRI (117276), and EXPLO-CRD-004, as well as preliminary mRNA-1273 
Phase I and Phase II data [Jackson, 2020; Chu, 2021]. 

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After final assay evaluations and validations, should the primary mRNA-1273 endpoint 
be replaced by SARS-CoV-2 neutralizing antibody titers, the same assumptions will be 
made since the standard deviation used for calculations was at the upper range of what 
has been observed for both endpoints; thus, the sample sizes presented below will remain 
for each cohort. 
The type I error to be maintained is 0.025 (one-sided) for each study cohort (HZ/su and 
mRNA-1273 booster, Flu D-QIV and mRNA-1273 booster). Study success will be 
evaluated separately for each cohort. For the HZ/su and mRNA-1273 booster cohort, 
non-inferiority must be achieved for both hypothesis 1 and hypothesis 2. For the Flu D-
QIV and mRNA-1273 booster cohort, success must be achieved for both hypothesis 3 
and hypothesis 4. 
A total of 1546 participants will need to be enrolled and randomized between the 2 
cohorts. 
9.5.1. 
Sample size for HZ/su and mRNA-1273 study cohort 
The global power considers meeting the primary objectives in the HZ/su and mRNA-
1273 booster cohort – with 245 evaluable participants in the HZ/suCoAd and HZ/suSeq 
groups the global power is approximately 90%. A GMC ratio of 1.1 between HZ/suSeq 
and HZ/suCoAd is assumed. Assuming 10% of the participants randomized are non-
evaluable (e.g. due to drop out/protocol violation), approximately 546 participants will 
need to be randomized (273 participants each in the HZ/suCoAd and HZ/suSeq groups). 
Note: If the dose of mRNA-1273 booster is adjusted while the study is ongoing, the 
sample size will be compensated in this cohort to ensure that there are enough 
evaluable participants in each group. (Amended 21 September 2021) 
Sample size calculations for the HZ/su and mRNA-1273 booster study cohort can be 
found in Table 18. 
Table 18 
Sample size calculations for HZ/su and mRNA-1273 booster study 
cohort 
Endpoint 
Number of Evaluable 
Participants per 
Cohort 
 
Standard 
Deviation 
Reference  
Assumed 
NI 
 
Total  
Power 
Post dose 2 HZ/su Non-inferiority* (1-sided test) – Primary Endpoint 
Post-Dose 2 GMC 
Ratio (Sequential vs. 
Co-Ad) anti-gE 
245 
0.025 
0.35 
1.1 
1.5 
1.1% 
98.9% 
mRNA-1273 booster vaccine: Non-inferiority* (1-sided test) – Primary Endpoint 
GMC Ratio 
(Sequential vs. Co-Ad) 
anti-S 
245 
0.025 
0.45 
1.1 
1.5 
8.9% 
91.1% 
Global  to show non-inferiority of the primary endpoints 
~10% 
 
Global power for the primary endpoints 
 
~90% 
Co-Ad = co-administered; GMC = geometric mean concentration 
* Pass 2019: alpha = 2.5% for HZ/su and mRNA-1273 booster GMC ratio; Non-Inferiority -Two Independent Means – 
Two-sample T-tests for Non-Inferiority Assuming Equal Variance 
For gE and mRNA-1273 booster vaccine: non-inferiority limit = 0.176 (=log10(1.5)), reference limit = 0.0413 
(=log10(1.1)). 

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SDs for HZ/su Dose 2 are taken from the average of the reference co-administration studies ZOSTER-004 (117036), 
ZOSTER-042 (116887), ZOSTER-035 (116889), ZOSTER-048 (201198), ZOSTER-059 (204487), FLU D-QIV-008 
(114269), FLU D-QIV-010 PRI (117276), and EXPLO-CRD-004. SDs for mRNA-1273 booster are taken from 
preliminary mRNA-1273 Phase I and II data.  
9.5.2. 
Sample size for Flu D-QIV and mRNA-1273 booster study cohort 
The non-inferiority of Flu D-QIV using GMTs (hypothesis 3) will be tested with a 1-
sided type I error of 0.025 for all 4 strains in the Flu D-QIV vaccine. No adjustment is 
needed for the type I error due to multiple comparison of Flu D-QIV 4 strains since one 
wants to reject the null hypothesis if one comparison is not conclusive.  
The non-inferiority of Flu D-QIV using SCR difference for 4 strains (Flu D-QIV 
and/mRNA-1273 booster cohort secondary endpoint, hypothesis 5) will be tested using a 
sequential approach, meaning, hypothesis 3 and 4 (GMT, Flu D-QIV and mRNA-1273 
booster primary endpoint) must be tested and non-inferiority of Flu D-QIV and mRNA-
1273 booster using GMT ratio must be demonstrated before hypothesis 5 is tested. Both 
tests will use a type I error of 0.025. Study success on the Flu D-QIV and mRNA-1273 
booster cohort will be declared if hypothesis 3 and 4 are met. Therefore, the power to 
achieve success for Flu D-QIV and mRNA-1273 booster cohort is driven by primary 
objectives for the Flu D-QIV and mRNA-1273 booster cohort. 
A GMC ratio of 1.1 between FluD-QIVSeq and FluD-QIVCoAd is assumed for the 
mRNA endpoint. A GMT ratio of 1.04 between FluD-QIVSeq and FluD-QIV is assumed 
for the flu endpoint. The global power considers meeting both primary objectives in the 
Flu D-QIV and mRNA-1273 booster cohort –with 450 evaluable participants in the FluD-
QIVCoAd and FluD-QIVSeq groups it is approximately 90.9%.  
The nominal power for the secondary objective to demonstrate non-inferiority in terms of 
SCR difference for each strain in the Flu D-QIV vaccine between FluD-QIVSeq and 
FluD-QIVCoAd groups is at least 85%. Assuming 10% of the participants randomized 
are non-evaluable (e.g. due to drop out/protocol violation), approximately 1000 
participants will need to be randomized (500 participants each in the FluD-QIVCoAd and 
FluD-QIVSeq groups). 
Sample size calculations for the Flu D-QIV and mRNA-1273 booster study cohort can be 
found in Table 19. 

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Table 19 
Sample size calculations for Flu D-QIV and mRNA-1273 booster 
study cohort 
 
Primary 
Endpoint 
Number of 
Evaluable 
Participants 
per Group 
 
Standard 
Deviation 
Reference  
Assumed 
NI 
 
Total  
Power 
FLU D-QIV Non-inferiority* (1-sided test) – 4 Strains – Primary Endpoint on GMT ratio 
GMT Ratio 
(Sequential vs. Co-
Ad) – A/ H1N1 
strain 
450 
0.025 
0.6 
1.04 
1.5 
2.2% 
97.8% 
GMT Ratio 
(Sequential vs. Co-
Ad) – A/H3N2 
strain 
450 
0.025 
0.6 
1.04 
1.5 
2.2% 
97.8% 
GMT Ratio 
(Sequential vs. Co-
Ad) – B/Victoria 
lineage 
450 
0.025 
0.6 
1.04 
1.5 
2.2% 
97.8% 
GMT Ratio 
(Sequential vs. Co-
Ad) – B/Yamagata 
lineage 
450 
0.025 
0.6 
1.04 
1.5 
2.2% 
97.8% 
mRNA-1273 booster vaccine: Non-inferiority* (1-sided test) – Primary Endpoint 
GMC Ratio 
(Sequential vs. 
Co-Ad) 
450 
0.025 
0.45 
1.1 
1.5 
0.6% 
99.4% 
Global  to show non-inferiority of the primary endpoints 
~9.1% 
 
Global power for the primary endpoints 
 
~90.9% 
 
FLU D-QIV Non-inferiority* (1-sided test) – 4 Strains – Secondary Endpoint on SCR difference  
Secondary Endpoint 
Number of 
Evaluable 
Participants 
per Group 
α 
Threshold 
SCR 
Assumed 
Total b 
Power 
SCR difference (Sequential vs. Co-
Ad) – A/H1NI strain 
450 
0.025 
10% 
78.6% 
4.5% 
95.5% 
SCR difference (Sequential vs. Co-
Ad) – A H3N2 strain 
450 
0.025 
10% 
70.3% 
9.2% 
90.8% 
SCR difference (Sequential vs. Co-
Ad) – B/Victoria lineage 
450 
0.025 
10% 
53.8% 
14.9% 
85.1% 
SCR difference (Sequential vs. Co-
Ad) B/Yamagata lineage 
450 
0.025 
10% 
56.9% 
14.0% 
86.0% 
GMT = geometric mean titer; SCR = seroconversion rate 
* Pass 2019: alpha = 2.5% for GMT/GMC ratio; Non-Inferiority -Two Independent Means – Two-sample T-tests for 
Non-Inferiority Assuming Equal Variance.  
**Pass 2019: alpha = 2.5% for SCR difference; Non-inferiority: Proportions – Two independent Proportions – Non-
Inferiority tests for Difference Between Two Proportions 
For Flu D-QIV and mRNA-1273 booster vaccine: non-inferiority limit = 0.176 (=log10(1.5)), reference limit = 0.0413 
(=log10(1.1)) for mRNA-1273 booster vaccine, reference limit = 0.017 (=log10(1.04)) for Flu D-QIV vaccine. 
SCR Assumptions come from the US participants in the FLU D-QIV-008 study. 
Participants who withdraw from the study will not be replaced. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
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. 
• 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted, to an IRB by the investigator 
for review and approval. These documents will be signed and dated by the 
investigator before the study is initiated. 
• 
Any protocol amendments will require IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. Furthermore, any substantial amendments to 
the protocol may require regulatory authority approval before implementation per 
local legislation. 
• 
PPD will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB. 
− 
Notifying the IRB of SAE(s) or other significant safety findings as required by 
IRB procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB, and all other applicable local 
regulations. 
• 
After reading the protocol, all principal investigators will sign the protocol signature 
page and send a copy of the signed page to PPD [see Investigator Agreement]. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide PPD with sufficient, accurate financial 
information as requested to allow GSK/PPD to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
study and for 1 year after completion of the study. 

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10.1.3. 
Informed consent process 
The investigator or his/her representative must fully 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.  
Freely given and written informed consent must be obtained from each participant, prior 
to participation in the study.  
The content of the informed consent form must meet the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB 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 consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF.  
Participants must be re-consented if a new version of the ICF(s) or an ICF addendum is 
released during their participation in the study. 
A copy of the ICF(s) must be provided to the participants. 
Participants who are rescreened are required to sign a new ICF. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by GSK/PPD. Any participant records or 
datasets transferred to GSK/PPD will contain only the identifier. Name and any other 
information which would identify the participant will not be transferred.  
The participants must be informed that: 
• 
His/her personal study-related data will be used by GSK in accordance with local 
data protection law.  
• 
His/her medical records may be examined by Clinical Quality Assurance auditors or 
other authorized personnel appointed by GSK/PPD, by appropriate IRB members, 
and by inspectors from regulatory authorities. 
GSK/PPD will ensure protection of the personal data of the investigator and study center 
staff which is collected within the framework of and for the purpose of the study, in 
accordance with the Data Privacy Notice that will be sent to the study center staff. 
The participants must be notified about their rights regarding the use of their personal 
data in accordance with the data privacy section of the ICF. 

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10.1.5. 
Committees structure 
Table 20 
Study administrative structure 
Function 
Responsible organization 
Clinical Supply Management, Quality Assurance Auditing 
GSK 
Laboratory Assessments 
GSK 
Randomization, Blinding, Unblinding 
Cenduit 
Study Operations Management, Medical Monitoring, Study Master File 
PPD 
Biostatistics, Medical Writing 
PPD 
Safety Review Team 
GSK 
Medical monitor 
Refer to the Safety and Medical Management Plan. 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocol summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical study registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results. The investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
GSK will provide the investigator with the randomization codes for their study center 
only after completion of the full statistical analysis. 
GSK intends to make anonymized patient-level data from this study available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and understanding. 

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10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (see Glossary of terms for the exact definition of 
essential and source documents). The document storage system used during the study and 
for archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential study documents may be added or removed where justified (in advance of study 
initiation) based on their importance and relevance to the study. When a copy is used to 
replace an original document (e.g. source documents, eCRF), the copy should fulfil the 
requirements for certified copies (see Glossary of terms for the exact definition of 
certified copies). 
All participant data related to the study will be recorded on printed or eCRF unless 
transmitted to GSK/PPD or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The investigator must maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the site’s study participants (see 
Glossary of terms for the exact definition of source documents) that supports information 
entered in the eCRF. 
The investigator must permit study-related monitoring, audits, IRB review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection.  
PPD is responsible for the data management of this study including quality checking of 
the source data (see Glossary of terms for the exact definition of source data). 
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be pre-defined in the Central Monitoring Plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These pre-defined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarized in the Clinical 
Study Report (CSR). 
Study records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance of the final 
CSR/equivalent summary 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 GSK. No records may be transferred to another location or party 
without written notification to GSK.  

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10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any 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. 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 
10.1.9. 
Study and site start and closure 
First act of recruitment 
The first act of recruitment is the date of the first participant enrollment and is considered 
the study start date. 
Study/Site termination  
GSK reserves the right to close the study site or terminate the study at any time for any 
reason at its sole discretion, provided there is sufficient notice given to account for all 
participants safe exit from study.  
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by GSK/PPD or investigator may include but 
are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB 
or local health authorities, GSK/PPD's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, GSK/PPD shall promptly inform the 
investigators, the IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up. 

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10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the Last Participant Last Visit (LPLV) for 
interventional studies and follows the guidance from the International Committee of 
Medical Journal Editors (ICMJE). 
10.2. 
Appendix 2: Adverse events: definitions and procedures for 
recording, evaluating, follow-up, and reporting  
10.2.1. 
Definition of an AE 
An AE is any untoward medical occurrence (an unfavorable/unintended sign - including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.2.1.1. 
Events meeting the AE definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g., hospital stays, physician 
visits and emergency room visits) 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (e.g. invasive procedures, modification of participant’s previous 
therapeutic regimen). Note this exception to AE definition for pre-intervention 
study-related events. 
• 
An SAE related to a GlaxoSmithKline concomitant medicine/vaccine with onset 
any time after signing the ICF. Note this exception to AE definition for pre-
intervention study-related events. 

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• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are present at baseline and significantly worsen following the start of the study 
will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited AEs are described in the Section 10.2.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
10.2.1.2. 
Events NOT meeting the AE definition 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.  
• 
Pre-existing conditions or signs and/or symptoms present in a participant before 
the first dose of study intervention (unless an untoward event with onset after 
signing the ICF and before first dose of study intervention that is either related to a 
study-procedure or is an SAE related to a GlaxoSmithKline concomitant 
medicine/vaccine). These events will be recorded in the medical history section of 
the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
10.2.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
d. Results in disability/incapacity 

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Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza like illness, and accidental trauma 
(e.g. sprained ankle) which may interfere or prevent everyday life functions but do 
not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant. 
f. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) 
g. Other situations 
Medical or scientific judgement must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition should be considered serious. 
Examples of such events are invasive or malignant cancers; intensive treatment in 
an emergency room or at home for allergic bronchospasm; blood dyscrasias; and 
convulsions that do not result in hospitalization. 
In addition: 
All suspected cases of anaphylaxis, in addition to being reported as an AESI, should be 
recorded as medically attended AEs and reported as an SAE, based on the criteria for a 
medically important event, unless the event meets other serious criteria. As an SAE, the 
event should be reported to PPD immediately and in all circumstances within 24 hours 
(per Section 10.2.10). The investigator will submit any updated anaphylaxis case data 
to PPD within 24 hours of it being available. For reporting purposes, a participant who 
displays signs or symptoms consistent with anaphylaxis (as follows) should be reported 
as a potential case of anaphylaxis. This is provided as general guidance for 
investigators and is based on the Brighton Collaboration case definition [Ruggeberg, 
2007]. 
Anaphylaxis is an acute hypersensitivity reaction with multi-organ system involvement 
that can present as, or rapidly progress to, a severe life-threatening reaction. It may 
occur following exposure to allergens from a variety of sources. 
Anaphylaxis is a clinical syndrome characterized by the following: 
• 
Sudden onset AND 
• 
Rapid progression of signs and symptoms AND 
• 
Involves 2 or more organ systems, as follows: 
− 
Skin/mucosal: urticaria (hives), generalized erythema, angioedema, 
generalized pruritus with skin rash, generalized prickle sensation, and red and 
itchy eyes. 

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− 
Cardiovascular: measured hypotension, clinical diagnosis of uncompensated 
shock, loss of consciousness or decreased level of consciousness, and 
evidence of reduced peripheral circulation. 
− 
Respiratory: bilateral wheeze (bronchospasm), difficulty breathing, stridor, 
upper airway swelling (lip, tongue, throat, uvula, or larynx), respiratory 
distress, persistent dry cough, hoarse voice, sensation of throat closure, 
sneezing, and rhinorrhea. 
− 
Gastrointestinal: diarrhea, abdominal pain, nausea, and vomiting. 
10.2.3. 
Solicited events 
10.2.3.1. 
Solicited local adverse events 
The following local AEs will be solicited at the time of the intervention: 
Table 21 
Solicited local adverse events 
Pain 
Redness 
Swelling 
Pruritus (for HZ/su vaccination only) 
Axillary (underarm) swelling or tenderness ipsilateral to 
the site of mRNA-1273 booster vaccination 
10.2.3.2. 
Solicited systemic events 
The following systemic events will be solicited: 
Table 22 
Solicited systemic events 
Fatigue 
Myalgia 
Headache 
Shivering/chills 
Fever 
Gastrointestinal symptoms (nausea, vomiting, diarrhea 
and/or abdominal pain) 
Arthralgia 
Note: Participants will be instructed to measure and record the body temperature, 
preferably in the evening, using the temperature measuring device provided by 
GSK/PPD. The recommended route of temperature measurement will be the oral route. If 
additional temperature measurements are taken at other times of the day, participants will 
be instructed to record the highest temperature in the eDiary. 
10.2.4. 
Unsolicited AEs 
An unsolicited AE is an AE that was either not included in the list of solicited events 
using a Participant Diary or could be included in the list of solicited events but with an 
onset more than 7 days following administration of a study intervention. Unsolicited 
events must have been communicated by a participant who has signed the informed 
consent. Unsolicited AEs include both serious and non-serious AEs. 

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Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or an emergency room visit, or visit to/by a health care 
provider). The participants will be instructed to notify the site as soon as possible to 
report medically attended events, as well as any events which, though not medically 
attended, are of participant’s concern or which prevent the participant from normal daily 
activities. Detailed information about reported unsolicited AEs will be collected by 
qualified site personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended, perceived as a concern by the 
participant, nor prevented normal daily activities, will still be collected during an 
interview with the participants and by review of available medical records at the next 
visit. 
10.2.5. 
Potential immune-mediated diseases 
pIMDs include autoimmune diseases and other inflammatory and/or neurologic disorders 
of interest which may or may not have an autoimmune etiology. AEs that need to be 
recorded and reported as pIMDs include those listed in the Table 23. 
The investigator must exercise his/her medical/scientific judgement to determine whether 
other diseases have an autoimmune origin (i.e. pathophysiology involving systemic or 
organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. 

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Table 23 
List of potential immune-mediated diseases (pIMDs) 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve neuropathy, including paralysis and paresis 
(e.g. Bell’s palsy) 
• 
Optic neuritis 
• 
Multiple sclerosis 
• 
Transverse myelitis 
• 
Guillain-Barré syndrome, including Miller Fisher syndrome 
and other variants 
• 
Acute disseminated encephalomyelitis, including site 
specific variants e.g.: non-infectious encephalitis, 
encephalomyelitis, myelitis, myeloradiculoneuritis 
• 
Myasthenia gravis, including Lambert-Eaton myasthenic 
syndrome 
• 
Demyelinating peripheral neuropathies including: 
− 
Chronic inflammatory demyelinating polyneuropathy  
− 
Multifocal motor neuropathy  
− 
Polyneuropathies associated with monoclonal 
gammopathy 
• 
Narcolepsy 
• 
Systemic lupus erythematosus and associated conditions 
• 
Systemic scleroderma (Systemic sclerosis), including: 
− 
Diffuse Scleroderma 
− 
CREST syndrome 
• 
Idiopathic inflammatory myopathies, including: 
• 
Dermatomyositis  
• 
Polymyositis  
• 
Anti-synthetase syndrome 
• 
Rheumatoid Arthritis and associated conditions including:  
− 
Juvenile Idiopathic Arthritis 
− 
Still’s disease 
• 
Polymyalgia rheumatica 
• 
Spondyloarthropathies, including:  
− 
Ankylosing Spondylitis  
− 
Reactive Arthritis (Reiter's Syndrome) 
− 
Undifferentiated Spondyloarthritis 
− 
Psoriatic Arthritis 
− 
Enteropathic arthritis 
• 
Relapsing Polychondritis. 
• 
Mixed Connective Tissue disorder 
• 
Gout 
• 
Psoriasis 
• 
Vitiligo 
• 
Erythema nodosum 
• 
Autoimmune bullous skin diseases 
(including pemphigus, pemphigoid and 
dermatitis herpetiformis) 
• 
Lichen planus 
• 
Sweet’s syndrome 
• 
Localised Scleroderma (Morphoea) 

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Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
− 
Giant Cell Arteritis (Temporal Arteritis) 
− 
Takayasu's Arteritis 
• 
Medium sized and/or small vessels vasculitis including:  
− 
Polyarteritis nodosa 
− 
Kawasaki's disease  
− 
Microscopic Polyangiitis  
− 
Wegener's Granulomatosis (granulomatosis with 
polyangiitis)  
− 
Churg–Strauss syndrome (allergic granulomatous 
angiitis or eosinophilic granulomatosis with 
polyangiitis)  
− 
Buerger’s disease (thromboangiitis obliterans)  
− 
Necrotising vasculitis (cutaneous or systemic)  
− 
Anti-neutrophil cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified) 
− 
Henoch-Schonlein purpura (IgA vasculitis)  
− 
Behcet's syndrome 
− 
Leukocytoclastic vasculitis 
• 
Autoimmune haemolytic anemia 
• 
Autoimmune thrombocytopenia 
• 
Antiphospholipid syndrome 
• 
Pernicious anemia 
• 
Autoimmune aplastic anemia 
• 
Autoimmune neutropenia 
• 
Autoimmune pancytopenia 
• 
Autoimmune glomerulonephritis 
including: 
− 
IgA nephropathy  
− 
Glomerulonephritis rapidly 
progressive  
− 
Membranous glomerulonephritis  
− 
Membranoproliferative 
glomerulonephritis  
− 
Mesangioproliferative 
glomerulonephritis  
− 
Tubulointerstitial nephritis and 
uveitis syndrome 
• 
Ocular autoimmune diseases including: 
− 
Autoimmune uveitis  
− 
Autoimmune retinitis 
• 
Autoimmune myocarditis 
• 
Sarcoidosis 
• 
Stevens-Johnson syndrome 
• 
Sjögren’s syndrome 
• 
Alopecia areata 
• 
Idiopathic pulmonary fibrosis 
• 
Goodpasture syndrome 
• 
Raynaud’s phenomenon 

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Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
• 
Autoimmune cholangitis 
• 
Inflammatory Bowel disease, including: 
− 
Crohn’s disease 
− 
Ulcerative colitis  
− 
Microscopic colitis  
− 
Ulcerative proctitis 
− 
Celiac disease 
• 
Autoimmune pancreatitis 
• 
Autoimmune thyroiditis (Hashimoto 
thyroiditis) 
• 
Grave's or Basedow’s disease 
• 
Diabetes mellitus type I 
• 
Addison’s disease 
• 
Polyglandular autoimmune syndrome 
• 
Autoimmune hypophysitis. 
When there is enough evidence to make any of the above diagnoses, the AE must be reported as a pIMD. Symptoms, signs or conditions 
which might (or might not) lead to one of the above diagnoses, should be recorded and reported as AEs but not as a pIMD until the final 
or definitive diagnosis has been made, and alternative diagnoses eliminated or shown to be less likely. The reporting of pIMDs is 
restricted to study participants in the HZ/su and mRNA-1273 booster cohort. 

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10.2.6. 
Adverse events of special interest 
The following AESIs (Table 24) are medical concepts that may be related to COVID-19 
or are of interest in COVID-19 vaccine safety surveillance. Even if the events below 
occur in the setting of a COVID infection, the event should still be reported as an AESI if 
it is one of the medical concepts below.  
Table 24 
List of AESIs applicable to mRNA-1273 vaccine 
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, microangiopathy, 
coronary artery disease, arrhythmia, stress cardiomyopathy, heart 
failure, or acute myocardial infarction. 
• 
Myocarditis or pericarditis as defined per protocol Section 10.2.2, and 
follow reporting procedures in protocol Section 10.2.12 
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 umol/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 
Acute liver injury 
• 
Include events with idiopathic or autoimmune etiologies 
• 
Exclude events with clear alternate etiology (trauma, infection, tumor, 
etc.) 

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Medical Concept 
Additional Notes 
• 
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) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
• 
Kawasaki’s disease 
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 (e.g. gout, 
osteoarthritis, and trauma) 
New onset of or worsening of 
neurologic disease 
• 
Including but not limited to  
o 
Guillain-Barre 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  
• 
Anaphylaxis as defined per protocol Section 10.2.2.  
• 
Follow reporting procedures in protocol Section10.2.12 
Other syndromes 
• 
Fibromyalgia  
• 
Postural Orthostatic Tachycardia Syndrome  
• 
Chronic Fatigue Syndrome (Includes Myalgic encephalomyelitis and 
Post viral fatigue syndrome) 
• 
Myasthenia gravis 

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When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as an AESI. Symptoms, signs or conditions which might (or might not) lead to 
one of the above diagnoses, should be recorded and reported as AEs but not as an AESI 
until the final or definitive diagnosis has been made, and alternative diagnoses eliminated 
or shown to be less likely. 
Any case of suspected, probable, or confirmed myocarditis, pericarditis, or 
myopericarditis should be reported as an AESI, even if it does not meet criteria per the 
CDC case definition. The event should also be reported as an SAE if it meets any 
seriousness criterion listed in Section 10.2.2. The following CDC case definition 
[Gargano, 2021] is provided as guidance: 
Acute Myocarditis: 
PROBABLE CASE: 
Presence of ≥1 new or worsening of the following clinical symptoms*: 
• 
chest pain, pressure, or discomfort; 
• 
dyspnea, shortness of breath, or pain with breathing 
• 
palpitations 
• 
syncope 
AND 
≥1 new finding of 
• 
troponin level above upper limit of normal (any type of troponin) 
• 
abnormal electrocardiogram or rhythm monitoring findings consistent with 
myocarditis§ 
• 
abnormal cardiac function or wall motion abnormalities on echocardiogram 
• 
cardiac magnetic resonance imaging (cMRI) findings consistent with myocarditis¶  
AND 
• 
No other identifiable cause of the symptoms and findings 
CONFIRMED CASE: 
Presence of ≥1 new or worsening of the following clinical symptoms*: 
• 
chest pain, pressure, or discomfort; 
• 
dyspnea, shortness of breath, or pain with breathing 
• 
palpitations 
• 
syncope 
AND 

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≥1 new finding of 
• 
histopathologic confirmation of myocarditis† 
• 
cMRI findings consistent with myocarditis¶ in the presence of troponin level above 
upper limit of normal (any type of troponin) 
AND 
No other identifiable cause of the symptoms and findings 
Acute Pericarditis** 
Presence of ≥2 new or worsening of the following clinical features: 
• 
acute chest pain†† 
• 
pericardial rub on exam 
• 
new ST-elevation or PR-depression on electrocardiogram 
• 
new or worsening pericardial effusion on echocardiogram or MRI 
* Persons who lack the listed symptoms but who meet other criteria may be classified 
as subclinical myocarditis (probable or confirmed). 
† Using the Dallas criteria [Aretz, 1987]. Autopsy cases may be classified as confirmed 
clinical myocarditis on the basis of meeting histopathologic criteria if no other 
identifiable cause. 
§ To meet the electrocardiogram or rhythm monitoring criterion, a probable case must 
include at least one of i) ST-segment or T-wave abnormalities; ii) Paroxysmal or 
sustained atrial, supraventricular, or ventricular arrhythmias; or iii) atrioventricular 
nodal conduction delays or intraventricular conduction defects. 
¶ Using either the original or the revised Lake Louise criteria [Ferreira, 2018].  
** [Adler, 2015].  
†† Typically described as pain made worse by lying down, deep inspiration, or cough, 
and relieved by sitting up or leaning forward, although other types of chest pain might 
occur. 
Participants who meet criteria for both myocarditis and pericarditis may be described 
under myopericarditis.(Amended 21 September 2021) 
All cases of myocarditis or pericarditis reported in an expedited manner as AESIs (and if 
a seriousness criterion is met, SAEs) may also be reviewed by an independent safety 
endpoint adjudication committee created by Moderna. 

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10.2.7. 
COVID-19 cases 
COVID-19 cases identified during the study (as per standard of care) will be captured and 
reported using standard AE, medically-attended AE or SAE criteria, and routine 
procedures for recording, evaluation, follow-up, and reporting of AEs and SAEs should 
be followed in accordance with the time period set out in the protocol. 
Diagnosis and categorization of COVID-19 cases for reporting purposes should be made 
in accordance with the following primary and secondary [Baden, 2021], and tertiary case 
definitions: 
Primary Case Definition: 
• 
The participant must have experienced at least TWO of the following systemic 
symptoms: fever (temperature ≥ 38ºC), chills, myalgia, headache, sore throat, new 
olfactory and taste disorder(s), OR 
• 
The participant must have experienced at least ONE of the following respiratory 
signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or 
radiographical evidence of pneumonia; AND 
• 
The participant must have at least one nasopharyngeal (NP) swab, nasal swab, or 
saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by 
PCR 
Secondary Case Definition: 
Defined as the following systemic symptoms: fever (temperature ≥ 38ºC), or chills, 
cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, 
headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea 
or vomiting, or diarrhea AND a positive NP swab, nasal swab, or saliva sample (or 
respiratory sample, if hospitalized) for SARS-CoV-2 by PCR 
Tertiary Case Definition: 
Documented diagnosis of COVID-19 made by a health care provider and not meeting the 
primary or secondary case definitions. 
10.2.8. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings assessments or other 
abnormal results the investigator considers clinically significant will be recorded as an 
AE or SAE, if they meet the definition of an AE or SAE (refer to Sections 10.2.1 and 
10.2.2).  
The investigator must exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 

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10.2.9. 
Events or outcomes not qualifying as AEs or SAEs 
10.2.9.1. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
Female participants who become pregnant after administration of the study intervention 
may continue the study at the discretion of the investigator. 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy 
outcome or complication or elective termination of a pregnancy for medical reasons will 
be recorded and reported as an SAE. Please refer to Section 10.2.2 for definition of SAE. 
10.2.10. 
Recording and follow-up of AEs, SAEs, AESIs, pIMDs, IMCs and 
pregnancies 
The participants will be instructed to contact the investigator immediately should they 
experience any signs or symptoms they perceive as of concern. 
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g., hospital progress notes, laboratory and diagnostics reports) related 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE on the eCRF. The investigator may not send photocopies of the participant’s 
medical records to PPD instead of appropriately completing the eCRF. 
There may be instances when copies of medical records for certain cases are requested by 
PPD. In this case, all participant identifiers will be blinded on copies of the medical 
records prior to submission to PPD. 
The investigator will attempt to establish a diagnosis pertaining to the event, based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE instead of individual signs/symptoms. 
An eDiary will be used in this study to capture solicited local or systemic events. The 
participant should be trained on how and when to complete the eDiary. 
Anyone who measures local or systemic events and who will record the event in the 
eDiary should be trained on using the eDiary. This training must be documented in the 
participant’s source record. Site staff will monitor eDiary compliance and the investigator 
will review and verify eDiary entries during discussions with the participant. 
Any unreturned eDiary will be sought from the participant through telephone call(s) or 
any other convenient procedure. 
Refer to the Monitoring Plan for more information regarding the use of eDiary. 

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10.2.10.1. Time period for collecting and recording AEs, SAEs, AESIs, pIMDs, and 
IMCs 
All solicited events that occur during the 7 days (Day 1-Day 7) following administration 
of each dose of study intervention must be recorded into the eDiary, irrespective of 
intensity. All other AEs occurring within the timeframes for collecting and reporting 
noted in Section 8.3.1 should be recorded into the appropriate section of the eCRF, 
irrespective of their intensity or whether or not they are considered related to the study 
intervention. 
10.2.10.2. Follow-up of AEs, SAEs, AESIs, pIMDs, and IMCs 
After the initial AE/SAE/AESI/pIMD/and IMC, the investigator is required to proactively 
follow each participant at subsequent visits/contacts. All SAEs, AESIs, pIMDs, and 
IMCs will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up.  
Other non-serious AEs must be followed until the end of the study or until the participant 
is lost to follow-up. 
10.2.10.2.1. 
Follow-up during the study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until the last 
visit/contact of the participant. 
If a participant dies during their participation in the study or during a recognized follow-
up period, PPD will be provided with any available post-mortem findings, including 
histopathology. 
10.2.10.2.2. 
Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to PPD on a 
previously reported SAE/AESI/pIMD using an electronic Expedited Adverse Events 
Report. The investigator is obliged to perform or arrange for the conduct of supplemental 
clinical examinations/tests and/or evaluations to elucidate the nature and/or causality of 
the SAE/AESI/pIMD as fully as possible. 
10.2.10.2.3. 
Follow-up of pregnancies 
The investigator is required to proactively follow each pregnancy at subsequent 
visits/contacts. Pregnant participants will be followed to determine the outcome of the 
pregnancy. At the end of the pregnancy, whether full-term or premature, information on 
the status of the mother and child will be forwarded to PPD using the electronic 
pregnancy report and the Expedited Adverse Events Report if applicable. Generally, the 
follow-up period does not need to be longer than 6 to 8 weeks after the estimated date of 
delivery. 

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Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, if the investigator becomes aware of any SAE occurring as a result of a 
post-study pregnancy AND it is considered by the investigator to be reasonably related to 
the study intervention, he/she must report this information to PPD as described in the 
Section 10.2.12. 
10.2.10.3. Updating of SAE, AESI, pIMD, and pregnancy information after removal 
of write access to the participant’s eCRF 
When additional SAE, AESI, pIMD or pregnancy information is received after write 
access to the participant’s eCRF is removed, new or updated information should be 
recorded on the appropriate paper report, with all changes signed and dated by the 
investigator. The updated report should be faxed to PPD within the defined reporting 
timeframes specified in the Table 15. 
10.2.11. 
Assessment of intensity and toxicity 
10.2.11.1. Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 25 
Intensity scales for AEs 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.

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The maximum intensity of injection administration site redness/swelling and fever will be 
graded as follows: 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or 
indices, which are protected by third party copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or 
indices, which are protected by third party copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.

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10.2.11.2. Assessment of causality 
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgement. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB and/or SmPC and/or Prescribing Information for marketed products to assist in 
making his/her assessment. 
Causality should be assessed by the investigator using the following question: Is there a 
reasonable possibility that the unsolicited AE may have been caused by the study 
intervention? 
YES: 
There is a reasonable possibility that the study intervention contributed to the 
AE.  
NO: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention. There are other, more likely causes 
and administration of the study intervention is not suspected to have 
contributed to the AE. 
If an event meets the criteria to be determined ‘serious’ (see Section 10.2.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol-required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify).  
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to PPD. However, it is very important to record 
an assessment of causality for every event before submitting the Expedited Adverse 
Events Report to PPD.  

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The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The investigator may change his/her opinion of causality after receiving 
additional information and update the SAE information accordingly. 
10.2.11.3. Medically attended visits 
For each solicited and unsolicited AE the participant experiences, the participant will be 
asked if he/she received medical attention (defined as hospitalization, or an otherwise 
unscheduled visit to or from medical personnel for any reason, including emergency 
room visits). This information will be recorded in the eCRF/Expedited Adverse Events 
Report as applicable. 
10.2.11.4. Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
10.2.12. 
Reporting of SAEs, AESIs, pIMDs, and pregnancies 
10.2.12.1. Events requiring expedited reporting to PPD 
Once an investigator becomes aware that a participant has experienced an 
SAE/AESI/pIMD/pregnancy, the investigator (or designee) must complete information in 
the electronic Expedited Adverse Events Report/electronic pregnancy report (as 
applicable) WITHIN 24 HOURS, even if the investigator does not have complete 
information on the SAE/AESI/pIMD/pregnancy. It must be completed as thoroughly as 
possible, with all available details of the event. 
The SAE/AESI/pIMD/pregnancy report must be updated WITHIN 24 HOURS of the 
receipt of updated information on the SAE/AESI/pIMD/pregnancy. The investigator will 
always provide an assessment of causality at the time of the initial SAE/AESI/pIMD 
report.  
Refer to the Table 14 for the details on timeframes for reporting of 
SAEs/AESIs/pIMDs/pregnancies. Refer to Section 10.2.12.2 for information on back-up 
systems in case the electronic reporting system does not work. 
The investigator will be required to confirm the review of SAE causality in the electronic 
Expedited Adverse Event Report within 72 hours of submission of the SAE. 

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SAE/AESI/pIMD/pregnancy reporting to PPD via an electronic data capture Tool 
• 
The primary mechanism for reporting an SAE/AESI/pIMD/pregnancy to PPD will 
be the electronic Data Capture (EDC) Tool. 
• 
If the EDC is unavailable for more than 24 hours, then the study center will use the 
paper Expedited AE Report or pregnancy report (as applicable). 
• 
The study center staff will enter the SAE/AESI/pIMD/pregnancy data into the EDC 
as soon as it becomes available. 
• 
After the study is completed at a given site, the EDC will be taken offline to prevent 
the entry of new data or changes to existing data. 
• 
If a study center receives a report of a new SAE from a participant or receives 
updated data on a previously reported SAE after the EDC has been taken offline, 
then the study center can report this information on a paper Expedited AE Report 
(see the next section). 
10.2.12.2. Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax a 
completed, dated and signed paper Expedited Adverse Events Report or pregnancy report 
(as applicable) to the study contact for reporting SAEs/AESIs/pIMDs/pregnancies (refer 
to Section 8.3.3.1) within 24 hours of becoming aware of the event.  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
or pregnancy report (as applicable) within 24 hours after the electronic reporting system 
is working again. The information reported through the electronic reporting system will 
be considered valid for regulatory reporting purposes. 

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10.3. 
Appendix 3: Contraceptive guidance and collection of 
pregnancy information 
10.3.1. 
Definitions 
10.3.1.1. 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.3.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal* 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth.  
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
*Note: If the childbearing potential changes after start of the study (e.g., a 
premenarchal female participant experiences menarche) or the risk of pregnancy 
changes (e.g., a female participant who is not heterosexually active becomes active), 
the participant must discuss this with the investigator, who should determine a highly 
effective method of contraception. If reproductive status is questionable, additional 
evaluation should be considered. 
• 
Premenopausal female with ONE of the following: 
− 
Documented total hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 
Note: Documentation can come from the study center personnel’s review of 
participant’s medical records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Alternatively, confirmation of post-menopausal status before 
study enrolment should be established. 

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10.3.2. 
Contraception guidance 
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
26).  
Table 26 
Highly effective contraceptive methods 
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulation 
• 
Oral 
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Injectable 
• 
Oral 
Highly Effective Methods That Are User Independent* 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual 
partner of the WOCBP, and the absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used.)  
Male partner sterilization prior to the female participant’s entry into the study, and this male is the sole partner 
for that participant, 
(The information on the male sterility can come from the study center personnel’s review of the participant’s medical 
records; medical examination and/or semen analysis, or medical history interview provided by her or her partner). 
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.)  
Female participants must practice adequate contraception for 30 days prior to 
vaccination, have a negative pregnancy test on the day of vaccination, and agree to 
continue adequate contraception during the entire intervention period and for 2 months 
after completion of the vaccination series. 
10.3.3. 
Collection of pregnancy information 
10.3.3.1. 
Female participants who become pregnant 
Refer to Sections 8.3.1, 8.3.2, 10.2.9.1, 10.2.10, and 10.2.10.2 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any female participant who becomes pregnant during the study will discontinue study 
intervention. 

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10.4. 
Appendix 4: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.4.1. 
Definition of medical device AE and adverse device effect (ADE) 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a medical device. This definition includes events related to the medical device 
or comparator and events related to the procedures involved. 
• 
An adverse device effect (ADE) is an AE related to the use of a medical device. This 
definition includes any AE resulting from: 
− 
Insufficient or inadequate instructions for use (i.e. user error), or 
− 
Any malfunction of a medical device, or 
− 
Intentional misuse of the medical device. 
10.4.2. 
Definitions of a medical device SAE, serious adverse device 
effect, and unexpected serious adverse device effect 
A Medical Device SAE is any SAE that: 
a. 
Led to death 
b. Led to serious deterioration in the health of the participant, that either resulted in: 
− 
A life-threatening illness or injury. The term “life-threatening” in the 
definition of “serious” refers to an event in which the participant was at risk of 
death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
− 
A permanent impairment of a body structure or a body function. 
− 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
− 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product 

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A Serious Adverse Device Effect (SADE) is: 
• A SADE is defined as an ADE that has resulted in any of the consequences 
characteristic of an SAE. 
• Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less fortunate. 
An Unanticipated SADE (USADE) is: 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
SADE that by its nature, incidence, severity or outcome has not been identified in 
the current version of the IB. 
10.4.3. 
Recording and reporting of medical device AE, ADEs, SADEs and 
USADE 
• 
The primary mechanism for reporting a medical device related event to PPD will be 
the EDC Tool. 
• 
If the EDC is unavailable for more than 24 hours or if a device eCRF is not 
available, then the study center will fax the paper “Medical device or combination 
product with device deficiency/incident report form” to PPD. 
• 
In rare circumstances and in the absence of Fax equipment, notification by phone is 
acceptable with a copy of “Medical device or combination product with device 
deficiency/incident report form” sent by overnight mail or courier service. 
• 
The study center staff will enter the medical device related event data into the EDC 
as soon as it become available. 
• 
Any device deficiencies must be reported to PPD within 24 hours after the 
investigator determines that the event meets the definition of a device deficiency. 
• 
Contact for reporting can be found in Section 8.3.3.1 
• 
PPD will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs as required by national regulations. 

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10.5. 
Appendix 5: Abbreviations and glossary of terms 
10.5.1. 
List of abbreviations 
AE 
adverse event 
AESI 
adverse event of special interest 
AESIs 
adverse events of special interest 
ANCOVA 
analysis of covariance 
AS 
adjuvant system  
AS01B 
adjuvant System 01B 
CBER 
Center for Biologics Evaluation and Research 
CD4 
cluster of differentiation 4 
CDC 
Center for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
cMRI 
cardiac magnetic resonance imaging 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
DLP 
data lock point 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ELISA 
enzyme linked immunosorbent assay 
EUA 
emergency use authorization 
FDA 
U.S. Food and Drug Administration 
Flu D-QIV 
quadrivalent seasonal influenza vaccine 
FluD-
QIVCoAd 
group receiving the mRNA-1273 booster dose co-administered with 
the Flu D-QIV dose 
FluD-QIVSeq 
group receiving the mRNA-1273 booster dose followed by the Flu D-
QIV dose 
GBS 
Guillain-Barré Syndrome 
gE 
glycoprotein E 
GMC 
geometric mean concentration 
GMT 
geometric mean titer 
HA 
hemagglutinin 
HI 
hemagglutinin inhibition 

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HRT 
hormone replacement therapy 
HZ 
herpes zoster 
HZ/su 
Herpes Zoster subunit vaccine  
HZ/suCoAd 
group receiving the mRNA-1273 booster dose co-administered with 
first dose of HZ/su 
HZ/suSeq 
group receiving the mRNA-1273 booster dose followed by the first 
dose of HZ/su 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonization 
ID 
identification number 
IgG 
immunoglobulin G 
IMC 
intercurrent medical condition 
IRB 
Institutional Review Board 
IRT 
Interactive Response Tool 
LNP 
lipid nanoparticle  
LPLV/LSLV 
last participant last visit/last subject last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGI 
mean geometric increase 
MM 
Medical Monitor 
MPL 
3-O-desacyl-4’-monophosphoryl lipid A 
mRNA 
messenger ribonucleic acid  
mRNA-1273 
mRNA-based vaccine against COVID-19 
N 
nucleocapsid 
NA 
neutralizing antibody 
NP 
nasopharyngeal 
OA 
older adults 
PCR  
polymerase chain reaction  
PHN 
postherpetic neuralgia 
pIMD 
potential immune mediated disease 
PPS 
per protocol set 
PT 
preferred term 
q.s 
quantum satis 
QS-21 
Quillaja saponaria Molina, fraction 21 
QTL 
quality tolerance limit 

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RBD 
receptor binding domain 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2  
SCR 
seroconversion rate 
SD 
Standard Deviation 
SoA 
schedule of activities 
SOC 
system organ class 
SPR 
seroprotection rate 
S-protein 
spike protein 
SRT 
safety review team 
su 
subunit 
UL 
upper limit 
VRR 
vaccine response rate  
VZV 
varicella zoster virus 
WHO 
World Health Organization 
YOA 
years of age 
10.5.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the use of a 
medicinal product, whether or not considered related to the 
medicinal product. 
An adverse event (AE) can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated 
with the use of a medicinal product. For marketed medicinal 
products, this also includes failure to produce expected benefits 
(i.e. lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the study are kept 
unaware of the intervention assignment in order to reduce the 
risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the study, and only when 
the data are cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required in case of a 
serious adverse event. 

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In an open-label study, no blind is used. Both the investigator 
and the participant know the identity of the intervention 
assigned. 
Caregiver: 
A caregiver is someone who 
• 
lives in the close surroundings of a participant and has a 
continuous caring role or 
• 
has substantial periods of contact with a participant and is 
engaged in his/her daily health care (e.g., a relative of the 
participant). 
In the context of a clinical study, a caregiver could include an 
individual appointed to oversee and support the participant's 
compliance with protocol specified procedures. 
Certified copy: 
A copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by 
generation through a validated process) to have the same 
information, including data that describe the context, content, 
and structure, as the original. 
Combination 
product: 
Combination product comprises any combination of 
• 
drug 
• 
device 
• 
biological product 
Each drug, device, and biological product included in a 
combination product is a constituent part. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrollment: 
The process of registering a participant into a clinical study by 
assigning participant identification number after signing the ICF. 
Enrolled 
participant: 
“Enrolled” means a participant’s agreement to participate in a 
clinical study following completion of the informed consent 
process. 
Essential 
documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of the data 
produced. 
eTrack: 
GSK’s tracking tool for clinical studies. 

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Evaluable: 
Meeting all eligibility criteria, complying with the procedures 
defined in the protocol, and, therefore, included in the per 
protocol analysis. 
Immunological 
correlate of 
protection: 
A correlate of risk that has been validated to predict a certain 
level of protection from the targeted endpoint. 
Intercurrent 
medical condition 
A condition that has the capability of altering the immune 
response to the study intervention or is confirmed to have an 
alteration of the participant’s initial immune status. 
Intervention: 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or placebo 
intended to be administered to a participant. 
Invasive medical 
device: 
A device which, in whole or in part, penetrates inside the body, 
either through a body orifice or through the surface of the body 
Investigational 
vaccine/product: 
A pharmaceutical form of an active ingredient being tested in a 
clinical study, including a product with a marketing authorization 
when used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain further 
information about an approved use. 
Investigator: 
A person responsible for the conduct of the clinical study at a 
study center. If a study is conducted by a team of individuals at a 
study center, the investigator is the responsible leader of the team 
and may be called the principal investigator. 
The investigator can delegate study-related duties and functions 
conducted at the study center to qualified individual or party to 
perform those study-related duties and functions. 
Interactive 
Voice/Web 
Response System: 
The software that enables the randomizing of participants into 
clinical trials and allocation of the study product to them in a 
blinded fashion. This technology allows study centers to interact 
with a database by pressing keypad buttons on a phone and 
following voice or online prompts in order to enter in 
information. 
Medical device 
deficiency: 
A device deficiency is an inadequacy of a medical device with 
respect to its identity, quality, durability, reliability, safety, or 
performance. Device deficiencies include malfunctions, use 
errors and information supplied by the manufacturer. 

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Medical Monitor 
PPD’s delegate providing significant scientific contribution to 
the conduct of the study. The terms Medical Officer, Medical 
Advisor are also used in some settings. 
Medically 
attended AEs: 
Symptoms or illnesses requiring hospitalization, or emergency 
room visit, or visit to/by a health care provider. 
Participant: 
Term used throughout the protocol to denote an individual who 
has been contacted to participate or participates in the clinical 
study, as a recipient of the study intervention 
(vaccine(s)/product(s)/control). 
Synonym: subject 
Participant ID: 
A unique identification number assigned to each participant who 
consents to participate in the study. 
Protocol 
amendment: 
The ICH defines a protocol amendment as “A written description 
of a change(s) to or formal clarification of a protocol.” GSK 
further details this to include a change to an approved protocol 
that affects the safety of participants, scope of the investigation, 
study design, or scientific integrity of the study. 
Randomization: 
Process of random attribution of intervention to participants to 
reduce selection bias. 
Safety Review 
Team: 
This team lead by safety comprises of core representatives from 
GSK global safety, clinical, epidemiology, regulatory, and 
statistics departments, who are also part of the study team and 
representatives from Moderna. For this study, this team is 
responsible for reviewing the safety data. 
Solicited events: 
Events to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively solicited 
from the participant or an observer during a specified follow-up 
period following study intervention administration. 
Source data: 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction and 
evaluation of the study. Source data are contained in source 
documents (original records or certified copies). 
Source 
documents: 
Original legible documents, data, and records (e.g., hospital 
records, clinical and office charts, laboratory notes, memoranda, 
participants' diaries or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm 

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or magnetic media, x-rays, participant files, and records kept at 
the pharmacy, at the laboratories and at medico-technical 
departments involved in the clinical study). 
Study/Center 
Monitor: 
An individual assigned by GSK/PPD (see the study 
administrative structure in Table 20) and responsible for assuring 
proper conduct of clinical studies at 1 or more study centers. The 
terms Clinical Research Monitor and Clinical Research 
Associate are used in some settings. 
Study 
intervention: 
Any investigational or marketed product(s) or placebo intended 
to be administered to a participant during the study. 
Treatment 
number: 
A number identifying intervention given to a participant, 
according to intervention allocation. 
Unsolicited 
events: 
Any AE reported in addition to those solicited during the clinical 
study. Also, any “solicited” symptom with onset outside of the 
specified period of follow-up for solicited symptoms will be 
reported as an unsolicited AE. 
10.6. 
Appendix 6: Protocol Amendment Summary of Changes 
10.6.1. 
Document history 
Document 
Date 
Protocol Final 
3 August 2021 
Amendment 1 Final 
21 September 2021 
Amendment 1 
Overall Rationale for the Amendment: 
This amendment is intended to modify the dose of each mRNA-1273 booster injection 
to 50 mcg from 100 mcg. 
10.6.2. 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
2.2 Background 
Moderna has been is evaluating the use of 50 µg 
(half dose) or 100 µg (full dose) of mRNA-1273 
as a booster vaccine in participants previously 
vaccinated with 2 doses of 100 µg mRNA-1273 
as a primary series. Available data indicates 
that boosting with half dose of the prototype 
mRNA-1273 has acceptable safety profile and 
induces robust neutralization titers against the 
Wuhan strain and variant viruses tested in all 
participants [Wu, 2021b]. It is however unclear 
if the half dose will sufficiently boost the 
immune response against other variants that 
Background for consideration of 
the 50 µg dose of the mRNA-
1273 vaccine. 

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Section # and Name 
Description of Change 
Brief Rationale 
are expected to emerge as the pandemic 
continues to evolve. Additional trials are 
underway to assess the safety and 
immunogenicity of different dose levels of the 
booster vaccines e.g.100 µg of mRNA-1273 
(clinicaltrials.gov: NCT04889209), as well as 
newly developed variant-specific vaccines 
(clinicaltrials.gov: NCT04927065).  
As of September 14th, 2021, the half dose (50 
µg) mRNA-1273 booster is one of the COVID-
19 booster vaccines recommended in the UK, 
to be administered at least 6 months after the 
primary series for certain populations at 
higher risk of severe COVID-19 disease. [JCVI 
2021] The half dose mRNA-1273 booster is 
under evaluation by other health agencies 
such as the European Medicines Agency and 
the US Food and Drug Administration. 
(Amended 21 September 2021) 
4.2 Scientific Rationale 
As of summer, 2021, vaccines against COVID-19 
in people ages 12 years and older have become 
an essential part of healthcare procedures to 
control the COVID-19 pandemic. With the 
emergence and spread of the SARS-CoV-2 
virus variants that may not be sufficiently 
controlled by the primary vaccinations,  
periodic administration of booster COVID-19 
vaccines after primary vaccination is either 
already recommended for specific populations 
or is under consideration by various health 
agencies may soon become necessary. 
Amended to reflect the current 
regulatory environment. 
4.3 Justification of 
dose. 
Moderna’s mRNA-1273 vaccine is authorized for 
use in the U.S in adults 18 YOA and older under 
an EUA by the FDA and as a primary series of 
two 100 µg doses administered 1 month apart. 
Doses of 100 µg and 50 µg of the same vaccine 
are being investigated as a potential booster dose 
to be administered following the primary series. 
Preliminary results have shown that a 50 µg 
mRNA-1273 booster dose at least 6 months 
following the primary series substantially 
increases neutralizing antibodies against the 
wildtype SARS-CoV-2 virus and other tested 
variants, with a safety profile consistent with the 
known profile in earlier clinical trials [Wu, 2021b]. 
Currently, in light of the evolving emergence of 
SARS-CoV-2 variants, it is anticipated that a 
booster vaccine may be is needed. The current 
available data suggests that 50 µg (half dose) 
of mRNA-1273 may be sufficient to boost 
immune response against the existing 
variants. This half dose is now recommended 
for boosting in the UK for certain populations 
at high risk for severe disease, to be 
administered 6 months post the primary 
series. This dose is also under review by other 
Justification of Moderna mRNA 
1273 booster dose reduction 
from 100 µg to 50 µg. 

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Section # and Name 
Description of Change 
Brief Rationale 
health agencies most effective. As a result, 50 
µg of mRNA-1273 will be used in this study.  
To note: If a different dose of mRNA-1273 is 
approved and recommended for use as a 
booster in the US while the study is ongoing, 
the dose of mRNA-1273 booster in the study 
will be adjusted in the HZ/su and mRNA-1273 
booster cohort to the approved dose. The 
sample size in this cohort will also be adjusted 
accordingly to ensure sufficient power to 
achieve the corresponding primary objectives 
with the adjusted dose. The data generated 
with the 50 µg of mRNA-1273 booster will then 
be informative and add to the body of safety 
and immunogenicity data at this dose level.  
(Amended 21 September 2021) 
6.3.2 Randomization to 
study intervention 
The stratification by age will be set to target 
ensure a minimum of 75 participants in the ≥ 65 
YOA stratum in each group. This minimum 
number of participants will provide sufficient data 
for analysis of CBER criteria for SPR and SCR by 
age category. 
Due to a later than anticipated 
start to the study, potential 
elderly participants may have 
mostly already received their 
seasonal influenza vaccines and 
no longer be eligible. 
9.5.1 Sample size for 
HZ/su and mRNA-1273 
study cohort 
Note: If the dose of mRNA-1273 booster is 
adjusted while the study is ongoing, the 
sample size will be compensated in this 
cohort to ensure that there are enough 
evaluable participants in each group. 
Unlike seasonal influenza 
unpredictability, we would still 
be able to continue the study 
and re-estimate sample size 
requirements for the HZ/su and 
mRNA-1273 study cohort and 
make details explicit in a 
subsequent protocol 
amendment. 
10.2.6 Adverse Events 
of Special Interest 
Any case of suspected, probable, or confirmed 
myocarditis, pericarditis, or myopericarditis 
should be reported as an AESI, even if it does 
not meet criteria per the CDC case definition. 
The event should also be reported as an SAE 
if it meets any seriousness criterion listed in 
Section 10.2.2.All cases of myocarditis or 
pericarditis with onset less than 7 days following 
mRNA-1273 administration, in addition to being 
reported as an AESI, should be recorded as 
causally related SAEs, based on the criteria for a 
medically important event, unless the event meets 
other serious criteria. As an SAE, the event 
should be reported to PPD immediately and in all 
circumstances within 24 hours (per Section 
10.2.12). The investigator will submit any updated 
myocarditis or pericarditis case data to PPD within 
24 hours of it being available. For reporting 
purposes, to ensure consistent case 
ascertainment, t The following CDC working 
case definition of myocarditis or pericarditis 
[Gargano, 2021] is provided as guidance. 
should be used: 
Text on AESI reporting of 
myocarditis and pericarditis 
made consistent with text in 
other Moderna protocols 
submitted to IND in past; 
thereby, also requiring moving 
from SAE section to AESI 
section in protocol. 
 

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11. 
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