A Phase II, Single-blind, Randomized, Controlled Study to Evaluate the Immunogenicity and Safety of a Measles, Mumps, Rubella, Varicella Vaccine Compared With ProQuad, Administered in Healthy Children 4-6 Years of Age
Phase: PHASE2
Conditions: Measles; Mumps; Rubella; Chickenpox, Measles
Sponsor: GlaxoSmithKline

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TITLE PAGE 
Protocol Title: A Phase II, single-blind, randomized, controlled study to evaluate the 
immunogenicity and safety of a measles, mumps, rubella, varicella vaccine compared with 
ProQuad, administered in healthy children 4 to 6 years of age 
Protocol Number: 217715 (MMRVNS 20-001) 
Product: Investigational measles, mumps, rubella, varicella vaccine (MMRVNS) 
Short Title: A study on the immune response and safety of a combined measles, mumps, 
rubella, chickenpox vaccine compared to a marketed combined vaccine, given to healthy 
children 4 to 6 years of age 
Study Phase: II 
Sponsor Name: GlaxoSmithKline Biologicals SA 
Legal Registered Address: Rue de l’Institut 89, Rixensart, 1330 Belgium 
IND Number: 28684 
EU CT Number: 2022-501564-18-00 
Original Protocol Date: 01 September 2022 
Amendment 1.0 Date: 15 March 2023 
 

C O N FI D E N TI A L  
 
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A me n d me nt 1 . 0 
 
 
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A p pr o v al D ate: 1 5  M a rc h 2 0 2 3  
 
S p o ns or Si g n at or y  
 
I h a ve rea d t his pr ot oc ol i n its e ntiret y a n d a gree t o c o n d uct t he st u d y acc or di n gl y: 
 
 
 
 
M d A hs a n H a bi b, M B B S, MI P H  
Cli nic al Pr oject Le a d  
Gl a x o S mit h Kli ne Bi ol o gic als S A  
 
D ate  
 
 
 
 
 
 
 
 
Refer t o t he St u d y Refere nce M a n u al f or Me dic al M o nit or’s n a m e a n d c o nt act 
i nf or m ati o n. 
 
P P D

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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
TABLE 
 
Table 1 
Document History 
DOCUMENT HISTORY 
 
 
Document 
Date 
Substantial 
Region 
Amendment 1.0 
15-March-2023 
No 
Global 
Original Protocol 
01-September-2022 
- 
- 
Amendment 1.0 (15-March-2023) 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union because it neither significantly impacts the safety or physical/mental integrity of 
participants nor the scientific value of the study. 
Overall Rationale for the Amendment: 
This protocol amendment was written to clarify the unblinding process in response to Request 
for Information from the European Medicines Agency. 
Table 2 
Description of the Most Important Changes in Amendment 1.0 
(additional text in bold italic; deletions in strikethrough) 
Section # and Name 
Description of Change 
Brief Rationale 
5.1 Inclusion Criteria 
Edited text: 
A male or female between, and 
including, 4 years and 6 years of 
age (i.e., from 4-year birthday until 
the day before the 7-year birthday) 
at the time of study intervention 
administration, and in accordance 
with local regulations. 
To ensure that within the 
protocol-specified age range, local 
regulations regarding age of vaccination 
are also followed.  
6.3.4 Blinding and 
Unblinding 
Added text: 
In addition, safety evaluation by 
IQVIA/GSK will be conducted in a 
blinded manner. 
Clarifying that the safety evaluation will 
be performed in a blinded manner. 
6.3.4.1 Emergency 
Unblinding 
Edited text:  
In case of emergency, the 
investigator and site staff will have 
unrestricted, immediate, and direct 
access to the participant’s 
individual study intervention 
through IVRS/IWRS.  
Investigator and site staff are not restricted 
to treatment and in order to unblind 
participant/caregiver investigator must use 
IVRS/IWRS.   
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
6.3.4.2 Unblinding 
Procedures for Safety 
Reporting 
Edited text: 
In case of unblinding, blind should 
be maintained for persons 
responsible for the ongoing conduct 
of the clinical study such as the 
management, monitors, 
investigators, and those persons 
responsible for data analysis and 
interpretation of results at the 
conclusion of the clinical trial, such 
as biometrics personnel.GSK’s 
Safety Review Team (SRT) 
performing blinded safety data 
review. 
Persons responsible for ongoing conduct 
of the study are not blinded for this study. 
Clarification is added to keep the SRT 
blinded during safety data review.  

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TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY .......................................................................................... 9 
1.1 
Synopsis ............................................................................................................ 9 
1.2 
Schema ............................................................................................................ 11 
1.3 
Schedule of Activities .................................................................................... 13 
2.0 
INTRODUCTION ..................................................................................................... 17 
2.1 
Study Rationale .............................................................................................. 17 
2.2 
Background .................................................................................................... 17 
2.3 
Benefit/Risk Assessment ............................................................................... 18 
2.3.1 
Risk Assessment ................................................................................ 18 
2.3.2 
Benefit Assessment ........................................................................... 19 
2.3.3 
Overall Benefit/Risk Conclusion ...................................................... 19 
3.0 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................... 20 
4.0 
STUDY DESIGN ....................................................................................................... 21 
4.1 
Overall Design ................................................................................................ 21 
4.2 
Scientific Rationale for Study Design .......................................................... 22 
4.3 
Participant Input into Design ....................................................................... 22 
4.4 
Justification for Dose ..................................................................................... 22 
4.5 
End of Study Definition ................................................................................. 23 
5.0 
STUDY POPULATION ............................................................................................ 24 
5.1 
Inclusion Criteria ........................................................................................... 24 
5.2 
Exclusion Criteria .......................................................................................... 24 
5.2.1 
Medical Conditions ........................................................................... 24 
5.2.2 
Prior/Concomitant Therapy ............................................................... 25 
5.2.3 
Prior/Concurrent Clinical Study Experience ..................................... 26 
5.2.4 
Other Exclusions ............................................................................... 26 
5.3 
Lifestyle Considerations ................................................................................ 27 
5.4 
Screen Failures ............................................................................................... 27 
5.5 
Criteria for Temporarily Delaying Enrollment and/or 
Intervention Administration ......................................................................... 27 
6.0 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .................... 28 
6.1 
Study Intervention(s) Administered ............................................................ 28 
6.2 
Preparation, Handling, Storage, and Accountability ................................. 31 
6.2.1 
Labeling ............................................................................................. 31 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................... 31 
6.3.1 
Participant Identification ................................................................... 31 
6.3.2 
Randomization to Study Intervention ............................................... 31 
6.3.3 
Intervention Allocation to Participants ............................................. 32 

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6.3.4 
Blinding and Unblinding ................................................................... 32 
6.4 
Study Intervention Compliance ................................................................... 34 
6.5 
Dose Modification .......................................................................................... 34 
6.6 
Continued Access to Study Intervention after the End of the 
Study ............................................................................................................... 34 
6.7 
Treatment of Overdose ................................................................................. 34 
6.8 
Concomitant Therapy ................................................................................... 34 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 35 
7.1 
Discontinuation of Study Intervention ........................................................ 35 
7.2 
Contraindications to Subsequent Study Interventions 
Administration ............................................................................................... 35 
7.3 
Participant Discontinuation/Withdrawal from the Study ......................... 35 
7.4 
Lost to Follow-up ........................................................................................... 36 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 37 
8.1 
Immunogenicity Assessments ....................................................................... 37 
8.1.1 
Biological samples ............................................................................ 37 
8.1.2 
Laboratory Assays ............................................................................. 38 
8.1.3 
Immunological Correlates of Protection ........................................... 38 
8.2 
Safety Assessments ........................................................................................ 39 
8.2.1 
Pre-intervention Administration Procedures ..................................... 39 
8.2.2 
Physical Examinations ...................................................................... 39 
8.2.3 
Clinical Safety Laboratory Tests ....................................................... 39 
8.2.4 
Safety Monitoring ............................................................................. 39 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 40 
8.3.1 
Time Period and Frequency for Collecting AE and SAEs 
and Other Safety Information ............................................................ 40 
8.3.2 
Method of Detecting AEs and SAEs ................................................. 40 
8.3.3 
Regulatory Reporting Requirements for SAEs ................................. 41 
8.3.4 
Reporting of Suspected Unexpected Serious Adverse 
Reactions to the EudraVigilance Database ....................................... 41 
8.3.5 
Annual Safety Report ........................................................................ 42 
8.3.6 
Urgent Safety Measures and Other Relevant Safety 
Reporting ........................................................................................... 42 
8.3.7 
Treatment of Adverse Events ............................................................ 42 
8.3.8 
Participant Card ................................................................................. 42 
8.4 
Study Procedures During Special Circumstances ...................................... 42 
8.5 
Pharmacokinetics .......................................................................................... 43 
8.6 
Pharmacodynamics ....................................................................................... 43 
8.7 
Genetics .......................................................................................................... 43 
8.8 
Biomarkers ..................................................................................................... 43 
8.9 
Immunogenicity Assessments ....................................................................... 44 
8.10 
Health Economics .......................................................................................... 44 

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9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 45 
9.1 
Statistical Hypotheses .................................................................................... 45 
9.2 
Analysis Sets ................................................................................................... 45 
9.3 
Statistical Analyses ........................................................................................ 45 
9.3.1 
General Considerations ..................................................................... 45 
9.3.2 
Primary Endpoint Analysis ............................................................... 45 
9.3.3 
Secondary Endpoints Analysis .......................................................... 46 
9.4 
Sequence of Analyses ..................................................................................... 48 
9.5 
Sample Size Determination ........................................................................... 48 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 49 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 49 
10.1.1 
Regulatory and Ethical Considerations ............................................. 49 
10.1.2 
Adequate Resources .......................................................................... 50 
10.1.3 
Financial Disclosure .......................................................................... 50 
10.1.4 
Recruitment Arrangements and Informed Consent and 
Assent Process ................................................................................... 50 
10.1.5 
Data Protection .................................................................................. 51 
10.1.6 
Study Administrative Structure ......................................................... 52 
10.1.7 
Safety Data Review and Data Monitoring Committee ..................... 52 
10.1.8 
Dissemination of Clinical Study Data ............................................... 53 
10.1.9 
Data Quality Assurance ..................................................................... 53 
10.1.10 Source Documents ............................................................................ 54 
10.1.11 Study and Study Center Start and Closure ........................................ 55 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 56 
10.3 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention .................................................................................................... 57 
10.3.1 
Definition of AE ................................................................................ 57 
10.3.2 
Definition of an SAE ......................................................................... 58 
10.3.3 
Solicited Events ................................................................................. 59 
10.3.4 
Unsolicited Adverse Events .............................................................. 59 
10.3.5 
Coronavirus Disease 2019 Cases ...................................................... 60 
10.3.6 
Assessment of Intensity ..................................................................... 60 
10.3.7 
Assessment of Causality ................................................................... 61 
10.3.8 
Medically Attended Visits ................................................................. 63 
10.3.9 
Assessment of Outcomes .................................................................. 63 
10.3.10 Reporting, Follow-up, and Assessment of AEs ................................ 63 
10.4 
Appendix 4: Abbreviations and Definitions ................................................ 67 
11.0 
REFERENCES .......................................................................................................... 73 
 
 

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LIST OF TABLES 
Table 1 
Document History .............................................................................................. 3 
Table 2 
Description of the Most Important Changes in Amendment 1.0 ........................ 3 
Table 3 
Schedule of Activities ....................................................................................... 13 
Table 4 
Intervals Between Study Visits ........................................................................ 16 
Table 5 
Risk Assessment and Risk Mitigation Strategy ................................................ 19 
Table 6 
Objectives and Endpoints ................................................................................. 20 
Table 7 
Study Groups, Interventions, and Blinding ...................................................... 21 
Table 8 
Study Interventions Administered .................................................................... 29 
Table 9 
Laboratory Assays ............................................................................................ 38 
Table 10 
Analysis Sets .................................................................................................... 45 
Table 11 
Assay Cut-off .................................................................................................... 46 
Table 12 
Study Administrative Structure ........................................................................ 52 
Table 13 
Solicited Administration Site Events ................................................................ 59 
Table 14 
Solicited Systemic Events ................................................................................ 59 
Table 15 
Intensity Scales for Solicited Symptoms in Children  
(4 to 6 Years of Age) ........................................................................................ 60 
 
LIST OF FIGURES 
Figure 1 
Study Schema ................................................................................................... 12 
 

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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Phase II, single-blind, randomized, controlled study to evaluate the 
immunogenicity and safety of a measles, mumps, rubella, varicella vaccine compared with 
ProQuad, administered in healthy children 4 to 6 years of age. 
Rationale: 
This study is designed to evaluate the immunogenicity and safety of GlaxoSmithKline 
Biologicals SA (GSK)’s investigational measles, mumps, rubella, varicella vaccine  
(hereafter referred to MMRVNS vaccine) compared with Merck’s measles, mumps, rubella, 
varicella vaccine, ProQuad (hereafter referred to as MMRV vaccine), when given as a second 
dose to children 4 to 6 years of age who were previously primed with a first dose of any 
combination of measles, mumps, rubella, and varicella-containing vaccine(s). 
This study will evaluate immunogenicity and safety using 3 MMRVNS formulations which 
vary for some or all of the individual virus potencies. The 3 MMRVNS formulations will be 
compared with the MMRV vaccine. In order to ensure representative data on the comparator, 
participants enrolled in the MMRV group will be randomized to 2 different lots. 
Concomitant administration of age-specific routine childhood diphtheria-tetanus-acellular 
pertussis-containing vaccines will be allowed according to the local immunization practices of 
the participating country. 

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Objectives and Endpoints: 
 
Objectives 
Endpoints 
Primary (Descriptive) 
To evaluate the immune response to the 
MMRVNS vaccines (formulated with different 
potencies) and the MMRV vaccine (pooled group) 
in terms of GMCs for antibodies to measles, 
mumps, rubella, and varicella viruses. 
• 
Anti-measles antibody GMCs at Day 43. 
• 
Anti-mumps antibody GMCs at Day 43. 
• 
Anti-rubella antibody GMCs at Day 43. 
• 
Anti-gE antibody GMCs at Day 43. 
Secondary (Descriptive) 
To evaluate the immune response to the 
MMRVNS vaccines (formulated with different 
potencies) and the MMRV vaccine (pooled group) 
in terms of seroresponse rates for antibodies to 
measles, mumps, rubella, and varicella viruses. 
• 
Anti-measles antibody seroresponse rate at Day 43. 
• 
Anti-mumps antibody seroresponse rate at Day 43. 
• 
Anti-rubella antibody seroresponse rate at Day 43. 
• 
Anti-gE antibody seroresponse rate at Day 43. 
To evaluate safety and reactogenicity following 
administration of the MMRVNS vaccines and the 
MMRV vaccine (pooled group). 
• 
Percentage of participants reporting each solicited 
administration site event during the 4-day period 
(day of administration and 3 following days) after 
the dose of study interventions*. 
• 
Percentage of participants reporting each solicited 
systemic event in terms of drowsiness and loss of 
appetite during the 4-day period (day of 
administration and 3 following days) after the dose 
of study interventions*. 
• 
Percentage of participants reporting each solicited 
systemic event in terms of fever, 
measles/rubella-like rash, varicella-like rash and 
other rash (not measles/rubella-like rash or 
varicella-like rash) during the 43-day period (day of 
administration and 42 following days) after the dose 
of study interventions*. 
• 
Percentage of participants reporting unsolicited AEs 
during the 43-day period (day of administration and 
42 following days) after the dose of study 
interventions*. 
• 
Percentage of participants reporting SAEs after the 
dose of study interventions* up to study end. 
 
Abbreviations: AE = adverse event; gE = glycoprotein E; GMC = geometric mean concentration; 
MMRV = comparator measles, mumps, rubella vaccine; MMRVNS = investigational measles, mumps, rubella, 
varicella vaccine; SAE = serious adverse event 
*Study interventions: MMRV(H)NS vaccine, MM(H)RVNS vaccine, and M(L)M(L)R(L)V(L)NS 
(investigational vaccines) or MMRV vaccine Lot 1 and MMRV vaccine Lot 2 (comparator vaccine). 
Overall Design: 
This is a phase II, single-blind, randomized, controlled, multi-country study in healthy 
children of 4 to 6 years of age. Participants will be randomized to a single dose of MMRVNS 
vaccine (3 groups of participants each receiving one of the 3 different vaccine formulations 
[designated as MMRV(H)NS vaccine, MM(H)RVNS vaccine, and M(L)M(L)R(L)V(L)NS 
vaccine, respectively]) or a single dose of a comparator licensed MMRV vaccine (2 groups of 

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participants each receiving one of the 2 different lots of the MMRV vaccine [designated as 
MMRV_Lot 1 and MMRV_Lot 2], which will be pooled for the analyses). All participants 
will be required to have been previously primed with a first dose of any combination of 
measles, mumps, rubella, and varicella-containing vaccine(s). Randomization to one of the 
5 intervention groups will be performed in a 2:2:2:1:1 ratio prior to intervention. There will be 
3 study visits, at Day 1 (study intervention and blood sampling at Visit 1), Day 15 (virtual or 
in-person safety check at Visit 2), and Day 43 (blood sampling at Visit 3), as well as 1 safety 
call and 1 safety follow-up contact, at Day 2-3 and Day 181, respectively. 
Safety monitoring will be performed by an Independent Data Monitoring Committee 
composed of clinical experts, independent of the study and external to GSK and GSK’s 
designee, and an independent statistician. 
Number of Participants: Approximately 800 participants will be randomly assigned to one 
of the 5 intervention groups to provide approximately 200 participants per each MMRVNS 
group and 100 participants per each MMRV group to obtain at least 640 evaluable participants 
(160 in each MMRVNS vaccine group and 80 in each MMRV vaccine group). 
Intervention Groups and Duration: 
The intervention groups will be as follows: 
• MMRV(H)NS vaccine: measles, mumps, and rubella at release potency and VNS at high 
(H) potency 
• MM(H)RVNS vaccine: measles, rubella, and varicella at release potency and mumps at 
high (H) potency 
• M(L)M(L)R(L)V(L)NS vaccine: measles, mumps, rubella, and varicella, all at low (L) 
potency 
• MMRV_Lot 1 vaccine: measles, mumps, rubella, and varicella Lot 1 
• MMRV_Lot 2 vaccine: measles, mumps, rubella, and varicella Lot 2 
The total duration of study participation for an individual participant will be 181 days. 
Data Monitoring/Other Committee: Yes 
1.2 
Schema 
See Figure 1. 

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Figure 1 
Study Schema 
 
Study interventions: MMRV(H)NS, MM(H)RVNS, and M(L)M(L)R(L)V(L)NS = investigational vaccine in 3 
different formulations; MMRV_Lot 1 and MMRV_Lot 2 = comparator vaccine MMRV Lot 1 and Lot 2. 
Abbreviations: N = number of participants 
°Before study intervention administration. 
*Blood sample for anti-measles, anti-mumps, anti-rubella virus and anti-gE antibody measurements. 
# Contact (by telephone call or any other convenient procedure) for the safety follow-up will take place 6 months 
postdose of study interventions. 
Note: Visit 2 (Day 15) for review of post-vaccination safety data may be a virtual visit 
Healthy children aged 4 to 6 years will be enrolled in this study according to the inclusion and 
exclusion criteria (see Section 5.0). The participants will be randomized in a 2:2:2:1:1 ratio to 
one of the 5 intervention groups. 

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1.3 
Schedule of Activities 
Table 3 
Schedule of Activities 
Age  
4 to 6 years of age at the time of study intervention administration 
Notes 
Type of contact 
Visit 1  
Safety call 
Visit 2† 
Visit 3  
EoS 
Safety follow-
up contact 
 
Timepoints 
Day 1 
Day 2-3 
Day 15 
Day 43 
Day 181 
Informed consent/assent as appropriate 
● 
 
 
 
 
See Appendix 1 for details 
Check inclusion/exclusion criteria 
● 
 
 
 
 
See Section 5.1 and Section 5.2 for details 
Collect demographic data 
● 
 
 
 
 
See Section 8.2.1 for details 
Medical history 
● 
 
 
 
 
See Section 8.2.1 for details 
Vaccination history (protocol-specific vaccines 
including varicella-containing vaccine and measles-, 
mumps-, rubella-containing vaccine) 
● 
 
 
 
 
See Section 8.2.1 for details 
Physical examination 
● 
 
 
 
 
See Section 8.2.2 for details 
Randomization 
○ 
 
 
 
 
Country and center will be used as 
minimization factors. See Section 6.3.2 for 
details 
Study interventions 
See Appendix 4 for the definition 
Check contraindications, warnings, and precautions 
to study intervention administration 
○ 
 
 
 
 
See Section 8.2.1 for details 
Check criteria for temporary delay for enrollment and 
study intervention administration 
● 
 
 
 
 
See Section 5.5 for details 
Study group and intervention number allocation 
○ 
 
 
 
 
See Section 6.3.3 for details 
Body temperature before study intervention 
administration 
● 
 
 
 
 
The preferred location for measuring 
temperature will be the axilla. Fever is 
defined as body temperature ≥38.0°C 
(100.4°F) 
Study intervention (MMRVNS/MMRV vaccine) 
administration 
● 
 
 
 
 
 

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Age  
4 to 6 years of age at the time of study intervention administration 
Notes 
Type of contact 
Visit 1  
Safety call 
Visit 2† 
Visit 3  
EoS 
Safety follow-
up contact 
 
Timepoints 
Day 1 
Day 2-3 
Day 15 
Day 43 
Day 181 
Recording of administered study intervention number 
● 
 
 
 
 
 
Distribute eDiaries/download the app 
○ 
 
 
 
 
An eDiary/personal electronic device app 
will be used to capture solicited 
administration site or systemic events. The 
participant’s parent(s)/LAR(s) should be 
trained on the use of the eDiary/app 
Laboratory Assessment  
Blood sampling for antibody determination (5 mL) 
●* 
 
 
● 
 
See Section 8.1.1 for details 
Safety assessments 
Record any concomitant medications/vaccinations 
● 
● 
● 
● 
 
See Section 6.8 for details 
Record any intercurrent medical conditions 
 
 
 
● 
 
See Section 9.2 for details 
Phone contact for safety follow-up 
 
● 
 
 
● 
Or any other convenient procedure 
Recording of solicited administration site events 
(Days 1–4 post dosing) 
○ 
○ 
 
 
 
Only events at the MMRVNS vaccine or 
MMRV vaccine administration site will be 
solicited 
Recording of solicited systemic events (drowsiness 
and loss of appetite) (Days 1-4 post dosing) 
○ 
○ 
 
 
 
See Section 8.3 for details and Appendix 3 
for definitions 
Safety follow-up with clinical staff to review 
post-vaccination safety data 
 
 
● 
 
 
 
Recording of solicited systemic events (fever, 
measles/rubella-like rash, varicella-like rash and 
other rash [not measles/rubella-like rash or 
varicella-like rash]) (Days 1–43 post dosing) 
○ 
○ 
○ 
○ 
 
See Section 8.3 for details and Appendix 3 
for definitions 
Recording of nonserious AEs (Days 1–43 post 
dosing) 
● 
● 
● 
● 
 
See Section 8.3 for details and Appendix 3 
for definitions 
eDiary/app completion reminder 
 
● 
 
 
 
 

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Age  
4 to 6 years of age at the time of study intervention administration 
Notes 
Type of contact 
Visit 1  
Safety call 
Visit 2† 
Visit 3  
EoS 
Safety follow-
up contact 
 
Timepoints 
Day 1 
Day 2-3 
Day 15 
Day 43 
Day 181 
Review of eDiaries/app data 
 
○ 
● 
● 
 
The study center staff should review that 
parent/LAR captured the info in the 
eDiaries/app before the eDiaries are 
returned or app uninstalled 
Return of eDiaries/uninstall or disable the app 
 
 
 
○ 
 
 
Recording of SAEs 
● 
● 
● 
● 
● 
See Section 8.3 for details and Appendix 3 
for definitions 
Recording of SAEs related to study participation, or 
to a concurrent GSK medication/vaccine 
● 
● 
● 
● 
● 
The collection and reporting periods start 
once the participants’ parent(s)/LAR(s) 
informed consent is obtained 
Study conclusion 
 
 
 
 
● 
See Section 4.5 for the definition of the 
end of study 
Abbreviations: AE = adverse event; App = application; eDiary = electronic diary; EoS = end of study; LAR = legally acceptable representative; MMRVNS = investigational 
measles, mumps, rubella, and varicella vaccine; MMRV = comparator measles, mumps, rubella, and varicella vaccine; SAE = serious adverse event 
Notes: 
The double-line border following Visit 3 (Day 43) indicates the analyses which will be performed on all data obtained up to Visit 3 (Day 43). 
● is used to indicate a study procedure that requires documentation in the individual electronic case report form (eCRF). 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
† Visit 2 (Day 15) may be conducted in-person or virtually. 
*Blood sampling before the study interventions. 
Note: If a participant is not able to visit the study center for any reason (including coronavirus disease 2019) they should contact the study center by telephone. Adverse event and 
concomitant medication details may be collected during a telephone call. It may not be possible to collect all clinical laboratory samples or conduct clinical assessments during this 
time, but any details should be recorded in the eCRF. If alternative arrangements can be agreed for the sample collection or clinical assessments, the details should be documented 
in the eCRF. 

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Table 4 
Intervals Between Study Visits 
Interval 
Planned visit interval* 
Allowed interval range 
Visit 1→Safety call 
1 to 2 days 
1-3 days 
Visit 1→Visit 2 
14 days 
14-19 days 
Visit 1→Visit 3 
42 days 
35-56 days 
Visit 1→Safety follow-up contact 
180 days 
180-201 days 
*The interval is the difference between the visit dates. 
Note: Whenever possible the investigator should arrange study visits following the planned visit interval. Deviation 
from allowed interval between Visit 1 and Visit 3 will lead to elimination from the Per Protocol Set. 

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2.0 INTRODUCTION 
2.1 
Study Rationale 
This study is designed to evaluate the immunogenicity and safety of GlaxoSmithKline 
Biologicals SA (GSK)’s investigational measles, mumps, rubella, varicella vaccine 
(MMRVNS vaccine) compared with Merck’s measles, mumps, rubella, varicella vaccine, 
ProQuad (hereafter referred to as MMRV vaccine), when given as a second dose to 
children 4 to 6 years of age who were previously primed (previously administered) with a 
first dose of any combination of measles-, mumps-, rubella-, and varicella-containing 
vaccine(s). 
This study will evaluate immunogenicity and safety using 3 MMRVNS formulations 
which vary for some or all of the individual virus potencies. The 3 MMRVNS 
formulations will be compared with the MMRV vaccine. In order to ensure representative 
data on the comparator, participants enrolled in the MMRV group will be randomized to 
2 different lots. Throughout the study, the 2 lots will be analyzed as a pooled group. 
The safety monitoring will be performed by an Independent Data Monitoring Committee 
composed of clinical experts, independent of the study and external to GSK and GSK’s 
designee, and an independent statistician. 
Concomitant administration of age-specific routine childhood diphtheria-, tetanus-, 
acellular pertussis (DTPa)-containing vaccines will be allowed according to the local 
immunization practices of the participating country. 
2.2 
Background 
Measles, mumps, rubella, and varicella are viral infections which can lead to serious 
complications, disability, and death of infected individuals or even in unborn children. 
To prevent measles, mumps, rubella, and varicella, the Advisory Committee on 
Immunization Practices (ACIP) in the United States (US) recommends a 2-dose measles, 
mumps, rubella, and varicella vaccine schedule in childhood. In the US, measles, mumps, 
rubella, and varicella vaccine can be administered from 12 months of age, with the 
routinely recommended age for the second dose at age 4 to 6 years. However, the second 
dose may be administered before the age of 4 years, provided that at least 3 months have 
elapsed since the first dose. In the US, MMRV vaccine is licensed for use among children 
from 12 months of age through 12 years of age [CDC, 2010]. 
In the European Union (EU), vaccination with 2 doses of measles, mumps, rubella, and 
varicella vaccine is recommended in different countries according to local and regional 
public health guidelines. MMRV vaccine is indicated for active immunization for the 
prevention of measles, mumps, rubella, and varicella in individuals over 12 months of 

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age. Applicable official recommendations may vary for countries regarding the interval 
between doses and the need for one dose or 2 doses of measles-, mumps-, and 
rubella- and of varicella-containing vaccines. 
Refer to the current Investigator’s Brochure (IB) for information regarding the 
MMRVNS vaccine, and to the current Prescribing Information/Package Insert/Summary 
of Product Characteristics for information regarding the comparator measles, mumps, 
rubella, and varicella vaccine, ProQuad. 
2.3 
Benefit/Risk Assessment 
2.3.1 
Risk Assessment 
The investigational MMRVNS vaccine is expected to have a benefit/risk profile similar 
to Merck’s ProQuad and GSK’s Priorix-Tetra vaccines. Detailed information about the 
expected risks and reasonably expected adverse events (AEs) of these 2 licensed measles, 
mumps, rubella, and varicella vaccines are summarized in the current IB. No new 
significant safety concerns have been identified in clinical trials and during post-
marketing use of these vaccines, at the time of finalizing this study protocol. 
All study activities at the study center will be performed by trained clinical staff 
authorized by the study investigator. For the safety of the participants, the protocol has 
incorporated appropriate inclusion and exclusion criteria  
(see Section 5.1 and Section 5.2), checking contraindications to vaccinations  
(see Section 8.2.1.2) and close monitoring of participants after vaccinations. 
The blinded monitoring of study data will be performed by GSK’s designee/Contract 
Research Organization (IQVIA) (see study administrative structure in Appendix 1). 
Additional unblinded safety monitoring will be performed by an IDMC composed of 
clinical experts, independent of the study and external to GSK and IQVIA, and an 
independent biostatistician. Monthly Safety Review Team (SRT) review by GSK will 
occur up to the completion of enrollment and vaccination of the first 200 participants, to 
monitor cumulative, blinded safety data (including serious and nonserious AEs)  
(see Section 8.2.4). 
IQVIA will immediately notify the investigators if any additional safety information 
becomes available during the study. This study will be performed in compliance with the 
protocol, International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), EU CTR, and 
applicable regulatory requirements. 
The risk assessment and mitigation strategy for this study are outlined in Table 5. 

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Table 5 
Risk Assessment and Risk Mitigation Strategy 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
 
Study Interventions – all study vaccines 
Local inflammatory reactions 
due to injection (i.e., pain, 
redness, swelling at the 
injection site, etc.) 
Subcutaneous vaccination 
commonly precipitates 
transient and self-limiting local 
inflammatory reactions (see 
the Investigator’s Brochure 
[IB] for details). 
Solicited local adverse events will 
be collected from each participant. 
Systemic reactions (i.e., fever, 
drowsiness, loss of appetite) 
Systemic adverse reactions to 
vaccination are common but 
generally mild to moderate in 
severity.  
Solicited systemic events will be 
collected for each participant. 
Medical advice as per the standard 
of care will be available. 
Systemic reactions such as 
measles/rubella-like rash, 
varicella-like rash 
Mild disease-like rashes may 
occur after administration of 
the study vaccine (see the IB 
for details). 
Measles/rubella-like rash, varicella-
like rash and other rash will be 
collected as solicited systemic 
events. 
Hypersensitivity reactions 
(including anaphylaxis) 
Acute allergic reactions such 
as an anaphylactic event may 
occur with any vaccine 
administration shortly after the 
intervention. These are serious, 
but rare occurrences. 
Participants with known 
hypersensitivity to any component 
of the vaccines will be excluded 
from enrollment. All participants 
will remain under observation for at 
least 30 minutes after vaccination. 
Study Procedures – Blood Sampling 
Pain and bruising 
Pain or bruising at the site 
where blood is drawn. 
A topical analgesic may be applied 
to the site where blood will be taken. 
Syncope 
Syncope (fainting) can occur 
following or even before any 
blood draw as a psychogenic 
response to the needle 
injection. 
All participants will remain under 
observation at the clinical center for 
at least 30 minutes after vaccination. 
2.3.2 
Benefit Assessment 
By receiving the MMRVNS vaccine or ProQuad the participants may potentially be 
protected against measles, mumps, rubella, and varicella disease. 
In addition, the participants will undergo a physical examination at the first study visit. In 
case the investigator discovers any medical condition, the participant will be referred to 
the local healthcare system. 
2.3.3 
Overall Benefit/Risk Conclusion 
The apparent risks associated with the study interventions are justified by the anticipated 
benefits that may be afforded to participants receiving the study interventions for the 
prevention of the above-mentioned diseases. 

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3.0 OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
 
Table 6 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary (Descriptive) 
To evaluate the immune response to the MMRVNS 
vaccines (formulated with different potencies) and the 
MMRV vaccine (pooled group) in terms of GMCs for 
antibodies to measles, mumps, rubella, and varicella 
viruses. 
• 
Anti-measles antibody GMCs at Day 43. 
• 
Anti-mumps antibody GMCs at Day 43. 
• 
Anti-rubella antibody GMCs at Day 43. 
• 
Anti-gE antibody GMCs at Day 43. 
Secondary (Descriptive) 
To evaluate the immune response to the MMRVNS 
vaccines (formulated with different potencies) and the 
MMRV vaccine (pooled group) in terms of 
seroresponse rates for antibodies to measles, mumps, 
rubella, and varicella viruses. 
• 
Anti-measles antibody seroresponse rate at Day 43. 
• 
Anti-mumps antibody seroresponse rate at Day 43. 
• 
Anti-rubella antibody seroresponse rate at Day 43. 
• 
Anti-gE antibody seroresponse rate at Day 43. 
To evaluate safety and reactogenicity following 
administration of the MMRVNS vaccines and the 
MMRV vaccine (pooled group). 
• 
Percentage of participants reporting each solicited 
administration site event during the 4-day period 
(day of administration and 3 following days) after 
the dose of study interventions*. 
• 
Percentage of participants reporting each solicited 
systemic event in terms of drowsiness and loss of 
appetite during the 4-day period (day of 
administration and 3 following days) after the dose 
of study interventions*. 
• 
Percentage of participants reporting each solicited 
systemic event in terms of fever, 
measles/rubella-like rash, varicella-like rash and 
other rash (not measles/rubella-like rash or 
varicella-like rash) during the 43-day period (day of 
administration and 42 following days) after the 
dose of study interventions*. 
• 
Percentage of participants reporting unsolicited 
AEs during the 43-day period (day of 
administration and 42 following days) after the 
dose of study interventions*. 
• 
Percentage of participants reporting SAEs after the 
dose of study interventions* up to study end. 
Abbreviations: AE = adverse event; gE = glycoprotein E; GMC = geometric mean concentration; MMRV = comparator 
measles, mumps, rubella vaccine; MMRVNS = investigational measles, mumps, rubella, varicella vaccine; 
SAE = serious adverse event 
*Study interventions: MMRV(H)NS vaccine, MM(H)RVNS vaccine and M(L)M(L)R(L)V(L)NS (investigational 
vaccines) or MMRV vaccine Lot 1 and MMRV vaccine Lot 2 (comparator vaccine). 
Estimands 
Estimands will be defined in the statistical analysis plan (SAP). 

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4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a phase II, single-blind, randomized, controlled, multi-country study in healthy 
children of 4 to 6 years of age. Participants will be randomized to a single dose of 
MMRVNS vaccine (3 groups of 200 participants each receiving one of the 3 different 
vaccine formulations [designated as MMRV(H)NS vaccine, MM(H)RVNS vaccine, and 
M(L)M(L)R(L)V(L)NS vaccine, respectively]) or a single dose of a comparator licensed 
MMRV vaccine (2 groups of 100 participants each receiving one of the 2 different lots of 
the MMRV vaccine [designated as MMRV_Lot 1 and MMRV_Lot 2], which will be 
pooled for all analyses). All participants will be required to have been previously primed 
with a first dose of any combination of measles-, mumps-, rubella-, and varicella-
containing vaccine(s). 
The study design diagram is provided in Figure 1. 
The study groups are shown in Table 7. 
Table 7 
Study Groups, Interventions, and Blinding 
Study groups  
Number of 
participants 
Age 
(Min-Max) 
Study interventions 
Blinding 
MMRV(H)NS 
200 
4 to 6 years 
MMRV(H)NS vaccine 
Single-blind 
MM(H)RVNS 
200 
4 to 6 years 
MM(H)RVNS vaccine 
M(L)M(L)R(L)V(L)NS 
200 
4 to 6 years 
M(L)M(L)R(L)V(L)NS vaccine 
MMRV_Lot 1 
100 
4 to 6 years 
MMRV vaccine Lot 1 
MMRV_Lot 2 
100 
4 to 6 years 
MMRV vaccine Lot 2 
The total duration of study participation for an individual participant will be 181 days. 
There will be 3 study visits: Visit 1 on Day 1, when the participants receive study 
intervention, Visit 2 on Day 15 (either in-person or virtually, for review of 
post-vaccination safety data), and Visit 3 on Day 43, when blood sampling for vaccine 
antibody testing will be performed. A safety call will be made on Day 2 or Day 3, and a 
safety follow-up contact will be made to the participant on Day 181 via telephone or by 
any other convenient means of communication. Refer to the Study Reference Manual 
(SRM) which will contain a guide telephone script to be used for the Day 2-3 safety call 
and for the Day 181 safety follow-up call. 
The visits/contacts should occur within a predefined visit window (see Table 4). 

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The study will be performed in a single-blind manner (see Section 6.3.4 for details). 
Furthermore, an IDMC comprising of clinical experts and a biostatistician will provide 
safety oversight during the active vaccination period, through unblinded review of the 
cumulative safety data. In addition, monthly SRT review by GSK will occur up to the 
completion of enrollment and vaccination of the first 200 participants, to monitor 
cumulative, blinded safety data (including serious and nonserious AEs)  
(see Section 8.2.4). 
4.2 
Scientific Rationale for Study Design 
Refer to Section 2.1 for rationale and Section 2.2 for background of the study. 
This is an active-controlled multi-country study. Concomitant administration of 
age-specific routine childhood DTPa-containing vaccines will be allowed according to 
the local immunization practices of the participating country to maintain the standard of 
care. 
To prevent measles, mumps, rubella, and varicella, the ACIP recommends a 2-dose 
measles, mumps, rubella, and varicella (MMRV) vaccine schedule in childhood. MMRV 
vaccine can be administered from 12 months of age, with the routinely recommended age 
for the second dose at age 4 to 6 years. Participating non-US countries will be those with 
vaccine schedule for the second dose aligned to that of the US. Also, the participants 
should have received their first MMRV vaccines during their second year of life. 
Because of the difference in the presentation of the investigational MMRVNS vaccine 
and the commercial MMRV vaccine, i.e., the difference in the labeling and presentation 
of the vaccine vials and diluent devices, the study will be conducted in a single-blind 
manner. See the definitions of single-blind in Appendix 4 and refer to Section 6.3 for 
details. 
4.3 
Participant Input into Design 
Not applicable. 
4.4 
Justification for Dose 
This study is intended to support licensure of GSK’s combined measles, mumps, rubella, 
and varicella vaccine (MMRVNS) in the US by generating immunogenicity and safety 
data in children 4 to 6 years of age. Only countries with measles, mumps, rubella, and 
varicella vaccine schedule aligned with ACIP recommendation in the US will be selected. 
The current recommendation by ACIP states that the first dose of MMRV vaccine be 
administered at the age of 12 to 15 months and the second dose is to be administered at 
the age of 4 to 6 years. Children who have not been vaccinated per the routine schedule 

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may be administered with the first dose of MMRV vaccine up to the age of 12 years in 
the US, but there is no upper age limit in the EU. Although the routinely recommended 
age for the second dose of MMRV vaccines is 4 to 6 years, the second dose may be 
administered before age 4 years, if ≥3 months have elapsed since the first dose, or up to 
the age of 12 years in the US. 
In line with the ACIP recommendation [ACIP, 2007], participants of age 4 to 6 years who 
have been previously primed with a first dose of any combination of measles-, mumps-, 
rubella-, and varicella-containing vaccine(s), will receive a single dose of the MMRVNS 
vaccine or the comparator MMRV vaccine in the current study. Refer to Section 6.1 for 
additional details. 
4.5 
End of Study Definition 
A participant is considered to have completed the study if he/she returns for the last 
visit/contact or is available for the last scheduled procedure/contact as described in the 
protocol. 
The end of the study (EoS) is defined as the date of the Last Participant Last Visit 
(LPLV), or date of last testing results released whichever comes last. In the latter, EoS 
must be achieved no later than 8 months after the LPLV. 

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
• Healthy participants as established by medical history and clinical examination 
before entering into the study. 
• A male or female between, and including, 4 years and 6 years of age (i.e., from 
4-year birthday until the day before the 7-year birthday) at the time of study 
intervention administration, and in accordance with local regulations. 
• Participant who previously received a first dose of varicella-containing vaccine 
in the second year of life. 
• Participant who previously received a single dose of measles-, mumps-, rubella-
containing vaccine in the second year of life. 
• Written informed consent obtained from the participants’ parent(s)/legally 
acceptable representative(s) (LAR[s]) prior to performance of any study-specific 
procedure (participant informed assent will be obtained from participants in line 
with local rules and regulations). 
• Participants’ parent(s)/LAR(s), who, in the opinion of the investigator, can and 
will comply with the requirements of the protocol (e.g., completion of electronic 
diaries [eDiaries], return for follow-up visits). 
 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
5.2.1 
Medical Conditions 
• History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions including hypersensitivity to neomycin or 
gelatin. 
• Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing 
required). 
• Hypersensitivity to latex. 
• Major congenital defects, as assessed by the investigator. 
• History of measles, mumps, rubella, or varicella disease. 

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• Recurrent history of or uncontrolled neurological disorders or seizures. 
• Acute disease at the time of enrollment. Acute disease is defined as the presence 
of a moderate or severe illness with or without fever. Fever is defined as body 
temperature ≥38.0°C (100.4°F) by any age-appropriate route. All study 
interventions can be administered to participants with a minor illness such as 
diarrhea, mild upper respiratory infection without fever. 
• Participant with history of coronavirus disease 2019 (COVID-19) who is still 
symptomatic. 
• Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study. 
5.2.2 
Prior/Concomitant Therapy 
• Use of any investigational or non-registered product (drug, vaccine, or medical 
device) other than the study interventions during the period beginning 30 days 
before the dose of study interventions (Day -29 to Day 1), or their planned use 
during the study period. 
• Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period 
starting 90 days prior to the study intervention administration. For 
corticosteroids, this will mean prednisone equivalent 0.5 mg/kg/day or 
20 mg/day whichever is the maximum dose for pediatric participants. Inhaled 
and topical steroids are allowed. 
• Administration of immunoglobulins and/or any blood products or plasma 
derivatives during the period starting 180 days before the dose of study 
interventions or planned administration during the study period. 
• Administration of long-acting immune-modifying drugs at any time during the 
study period (e.g., infliximab). 
• Previous vaccination with a second dose of varicella-containing vaccine or 
measles-, mumps-, rubella-containing vaccine. 
• Administration or planned administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before the dose and ending at 43 days after 
the dose of study interventions administration* (Visit 3), with the exception of: 
− 
inactivated influenza (flu) vaccine which may be given at any time during the 
study and administered at a different location than the study interventions and, 
− 
routinely recommended licensed childhood DTPa-containing vaccines which 
can preferably be co-administered according to the local immunization practices 
of the participating country. 
Any other age-appropriate vaccine may be given starting at Visit 3 and anytime 
thereafter. 

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*In case an emergency mass vaccination for an unforeseen public health threat  
(e.g., a pandemic) is recommended and/or organized by public health authorities 
outside the routine immunization program, the time period described above can be 
reduced if necessary for that vaccine, provided it is used according to the local 
government recommendations and that GSK/IQVIA is notified accordingly. 
5.2.3 
Prior/Concurrent Clinical Study Experience 
• Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational 
or a non-investigational intervention (drug/invasive medical device  
[see the definition in Appendix 4]). 
5.2.4 
Other Exclusions 
• Child in care (see the definition in Appendix 4). 
• Any study personnel’s immediate dependents, family, or household members. 
• Participants with the following high-risk individuals in their household: 
− Immunocompromised individuals (as defined in Section 5.2.1). 
− Pregnant women without documented history of varicella. 
− Newborn infants of mothers without documented history of varicella. 
− Newborn infants born <28 weeks of gestation.

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5.3 
Lifestyle Considerations 
No restrictions for this study. 
5.4 
Screen Failures 
Not applicable as there is no screening phase of the potential participants as part of this study. 
5.5 
Criteria for Temporarily Delaying Enrollment and/or Intervention 
Administration 
Enrollment and/or study intervention administration may be postponed within the permitted 
time interval until transient circumstances cited below are resolved and the participant stays 
eligible: 
• Acute disease and/or fever at the time of enrollment 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 the axilla. 
• Participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) 
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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6.0 STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
For the definition of study intervention, refer to Appendix 4. 
6.1 
Study Intervention(s) Administered 
The study interventions that will be administered in the study are provided in Table 8.

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Table 8 
Study Interventions Administered 
 
Study intervention 1 
Study intervention 2 
Study intervention 3 
Study intervention 4 
Study 
intervention name 
MMRV(H)NS vaccine 
MM(H)RVNS vaccine 
M(L)M(L)R(L)V(L)NS vaccine 
ProQuad 
Study 
intervention 
formulation (per 
dose) 
Live attenuated 
measles virus 
(Schwarz strain) 
(≥1×10³·⁰ CCID₅₀); 
Live attenuated 
mumps virus 
(RIT4385 strain) 
(≥1×104.2 CCID₅₀); 
Live attenuated 
rubella virus (Wistar 
RA 27/3 strain) 
(≥1×103.2 CCID₅₀); 
Live attenuated 
varicella virus (Oka 
strain) (≥1×102.9 pfu) 
Water for 
injections  
Live attenuated 
measles virus 
(Schwarz strain) 
(≥1×10³·⁰ CCID₅₀); 
Live attenuated 
mumps virus 
(RIT4385 strain) 
(≥1×104.2 CCID₅₀); 
Live attenuated 
rubella virus (Wistar 
RA 27/3 strain) 
(≥1×103.2 CCID₅₀); 
Live attenuated 
varicella virus (Oka 
strain) (≥1×102.9 pfu) 
Water for 
injections  
Live attenuated 
measles virus 
(Schwarz strain) 
(≥1×10³·⁰ CCID₅₀); 
Live attenuated 
mumps virus 
(RIT4385 strain) 
(≥1×104.2 CCID₅₀); 
Live attenuated 
rubella virus (Wistar 
RA 27/3 strain) 
(≥1×103.2 CCID₅₀); 
Live attenuated 
varicella virus (Oka 
strain) (≥1×102.9 pfu) 
Water for 
injections  
Live attenuated 
measles virus 
(Enders' 
Edmonston 
strain) (≥1×103.0 
TCID50); Live 
attenuated 
mumps virus 
(Jeryl-Lynn 
[Level B] strain) 
(≥1×104.3 
TCID50); Live 
attenuated 
rubella virus 
(Wistar RA 27/3 
strain) (≥1×103.0 
TCID50); Live 
attenuated 
varicella virus 
(OKA/Merck 
strain) 
(≥1×103.99 PFU) 
Water for 
injections 
q.s. 0.5 mL 
Presentation 
Powder for 
suspension for 
injection (Vial) 
Solution for 
suspension 
for injection 
(Syringe) 
Powder for 
suspension for 
injection (Vial) 
Solution for 
suspension 
for injection 
(Syringe) 
Powder for 
suspension for 
injection (Vial) 
Solution for 
suspension 
for injection 
(Syringe) 
Powder for 
suspension for 
injection (Vial) 
Solution for 
suspension 
for injection 
Type 
Investigational 
Investigational 
Investigational 
Control 
Product Category 
Biologic/Combination Product 
Biologic/Combination Product 
Biologic/Combination Product 
Biologic/Combination Product 
Route of 
administration 
Subcutaneous injection 
Subcutaneous injection 
Subcutaneous injection 
Subcutaneous injection 
Administration site 

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Study intervention 1 
Study intervention 2 
Study intervention 3 
Study intervention 4 
Location 
Arm 
Arm 
Arm 
Arm 
Directionality 
Upper 
Upper 
Upper 
Upper 
Laterality 
Left 
Left 
Left 
Left 
Number of doses 
to be 
administered 
1 
1 
1 
1 
Volume to be 
administered by 
dose* 
At least 0.5 mL 
At least 0.5 mL 
At least 0.5 mL 
0.5 mL 
Packaging and 
labeling  
Refer to Pharmacy Manual for 
details 
Refer to Pharmacy Manual for 
details 
Refer to Pharmacy Manual for 
details 
Refer to Pharmacy Manual for 
details 
Manufacturer 
GSK 
GSK 
GSK 
Merck & Co. 
Abbreviations: CCID50 = 50% cell culture infective dose; GSK = GlaxoSmithKline Biologicals SA; H = High potency; L = Low potency; PFU = plaque-forming units; 
q.s.= sufficient quantity; TCID50 =50% tissue culture infectious dose 
*Refer to the Pharmacy Manual for the volume after reconstitution. 
  

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6.2 
Preparation, Handling, Storage, and Accountability 
The study interventions will be prepared as described in the Pharmacy Manual. 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study can receive study intervention, and only authorized 
study site staff can supply or administer study intervention. All study interventions must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized study site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance  
(i.e., receipt, reconciliation, and final disposition records). 
The investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study intervention using the Drug 
Accountability Form. These forms must be available for inspection at any time. 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual. 
6.2.1 
Labeling 
Study vaccine will be appropriately labeled in order to ensure participant safety and the 
reliability and robustness of data generated in this study, and in order to allow for the 
distribution of vaccines to clinical study centers. 
Labeling details will be provided in the Pharmacy Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Participant Identification 
The participant identification numbers (IDs) will be assigned sequentially to the participants 
whose parent(s)/LAR(s) have consented to participate in the study, according to the range of 
participant IDs allocated to each study center. 
6.3.2 
Randomization to Study Intervention 
Country and center will be used as minimization factors for randomization. Randomization of 
vaccines will be performed using Interactive Voice Response System (IVRS)/Interactive Web 
Response System (IWRS). The participants will receive a unique treatment number  

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(refer to Appendix 4 for the definition). Once a treatment number has been assigned, it cannot 
be re-assigned. 
6.3.3 
Intervention Allocation to Participants 
Allocation of the participant to an intervention group at the study center will be performed 
using IVRS/IWRS randomization through Interactive Response Tool  
(IRT; refer to Appendix 4 for the definition) operated at the study level, before the first 
vaccination and after assessment of eligibility (i.e., after screening conclusion). The country 
and center will be used as minimization factors. 
The actual randomization assignment the participant received (to one of the groups) will be 
identifiable via IRT in case of unblinding. 
After obtaining the signed and dated informed consent form (ICF) from the participant’s 
parent(s)/LAR(s) and having checked the eligibility of the participant, the delegated clinical 
study staff will access IVRS/IWRS. Upon entering the participant ID, the randomization 
system will determine the intervention group and provide the treatment number. 
Refer to the IVRS/IWRS user guide or the SRM for specific instructions related to instances 
when IVRS/IWRS is not available. 
Refer to the SRM for additional information related to the treatment number allocation. 
6.3.4 
Blinding and Unblinding 
Data will be collected in a single-blind manner. The investigator(s) and/or their staff will be 
aware of the study intervention assignment, but the participant will not. The study intervention 
will be prepared and administered by qualified study personnel who can be aware of the 
intervention assignment. In addition, safety evaluation by IQVIA/GSK will be conducted in a 
blinded manner. 
Participants will be randomized in a 2:2:2:1:1 ratio to receive study intervention and will 
remain blinded to the study intervention throughout the course of the study. 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There will be 
no link between the study intervention and the identity of the participant. 
6.3.4.1 
Emergency Unblinding 
Unblinding a participant’s individual treatment number should occur ONLY in case of a 
medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 

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In case of emergency, the investigator and site staff will have immediate, and direct access to 
the participant’s individual study intervention through IVRS/IWRS. At activation, the study 
centers will be provided instructions and/or other applicable information for emergency 
unblinding. The IRT used by the IVRS/IWRS provider will be programmed with 
blind-breaking instructions. In case of an emergency, the investigator has the sole 
responsibility for determining if unblinding of a participant’s intervention is warranted. The 
participant safety must always be the first consideration in making such a determination. 
If a participant’s intervention assignment is unblinded, the Medical Monitor (see the definition 
in Appendix 4) must be notified within 24 hours after breaking the blind. The date and reason 
that the blind was broken must be recorded in the source documentation (see the definition in 
Appendix 4) and electronic case report form (eCRF), as applicable. The participant may 
continue in the study. 
In the event of a Quality Assurance audit, the auditor(s) may be allowed access to unblinded 
study treatment information records to verify that vaccine dispensing has been done 
accurately. 
A physician other than the investigator (e.g., an emergency room physician) or participant’s 
parent(s)/LAR(s)/caregiver (see the definition in Appendix 4)/family member may also 
request emergency unblinding. Instructions for this will be provided to the participants’ 
parent(s)/LAR(s) at enrollment. 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded. 
6.3.4.2 
Unblinding Procedures for Safety Reporting 
The investigator will only unblind the treatment allocation of a participant in the course of a 
clinical study if unblinding is relevant to the safety of the participant. 
When reporting a Suspected Unexpected Serious Adverse Reaction (SUSAR) to the European 
Medicines Agency (EMA), IQVIA will only unblind the treatment allocation of the affected 
participant to whom the SUSAR relates. 
In case of unblinding, blind should be maintained for GSK’s Safety Review Team (SRT) 
performing blinded safety data review. 
Unblinded information will be accessible only to persons who need to be involved in the 
safety reporting to the EMA, to the IDMC, or to persons performing ongoing safety 
evaluations during the clinical study. 

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6.4 
Study Intervention Compliance 
When the study intervention is administered at the study center, participants will receive it 
directly from the investigator or designee, under medical supervision. The date of 
administration of each study intervention dose in the clinic will be recorded in the source 
documents. 
6.5 
Dose Modification 
Dose modifications are not planned or allowed in this study. 
6.6 
Continued Access to Study Intervention after the End of the Study 
There will be no continuing access to study intervention after the end of the study. 
6.7 
Treatment of Overdose 
For this study, any dose of study intervention greater than the recommended dose per protocol 
will be considered an overdose. 
Overdose in itself is not to be reported as an AE, however, any AEs associated with the 
overdose are to be reported in the relevant AE/serious adverse event (SAE) sections of the 
eCRF. 
6.8 
Concomitant Therapy 
At each study visit/contact, the investigator(s) or their delegate(s) should question the 
participant’s parent(s)/LAR(s) about all medications/products taken, and vaccinations received 
by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the eCRF: 
• All concomitant medication associated with an AE, including vaccines/products, 
administered after the first dose of study intervention (Day 1 to Day 43). 
• All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines. 
• All concomitant medication which may explain/cause/be used to treat an SAE including 
vaccines/products, as defined in Section 8.3.1 and Appendix 3. These must also be 
recorded in the Expedited AE report. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. The record of a concomitant medication should include at a minimum, the 
reason for use, dates of administration including start and end dates, dosage information 
including dose and frequency. 

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7.0 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
Not applicable as this is a single dose study. 
7.2 
Contraindications to Subsequent Study Interventions Administration 
Not applicable as this is a single dose study. 
7.3 
Participant Discontinuation/Withdrawal from the Study 
The participant’s parent(s)/LAR(s) may withdraw the participant from the study at any time or 
the investigator may decide to withdraw a participant for safety, compliance, administrative, 
or other reasons. 
A participant is considered a “withdrawal” from the study when no study procedure has 
occurred, no follow-up has been performed, and no further information has been collected for 
this participant from 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. 
All data and samples collected up to and including the date of withdrawal of/last contact with 
the participant parent(s)/LAR(s) will be included in the study analyses. 
The primary reason for study withdrawal shall be documented in the eCRF. Examples of the 
reasons may include: 
• Adverse event requiring expedited reporting to IQVIA (see Appendix 3 for the details 
regarding such events) 
• Unsolicited nonserious AE 
• Solicited AE 
• Withdrawal by the participant’s parent(s)/LAR(s) but not due to AE* 
• Migrated/moved from the study area 
• Lost to follow-up 
• Study termination 
• Other (specify) 

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*If a participant is withdrawn from the study because the participant’s parent(s)/LAR(s) have 
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 SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. The investigators should 
follow-up with parent(s)/LAR(s) of participants who are withdrawn from the study as a result 
of an SAE/AE until the event is resolved (see Appendix 3 for details regarding follow-up for 
AEs). 
7.4 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she fails to return for scheduled visits 
and is unable to be contacted by the study center staff. 
Refer to the SRM for a description of actions to be taken before considering the participant 
lost to follow-up. 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (SoA) 
(Section 1.3). Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with IQVIA immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility. 
The SRM provides the investigator and study center personnel with detailed administrative 
and technical information that does not impact the participant safety. 
8.1 
Immunogenicity Assessments 
8.1.1 
Biological samples 
An overall volume of 10 mL (5 mL each at Visit 1 and Visit 3) per participant will be 
collected during the entire study period. 
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 study 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 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 Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) 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 participant’s 
parent(s)/LAR(s). 
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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8.1.2 
Laboratory Assays 
All laboratory testing will be performed as indicated in Table 9 at GSK laboratory or in a 
laboratory designated by GSK. The assay to measure immune responses to measles, mumps, 
and rubella are qualified for use in this Phase II study and will be validated for future Phase III 
studies in the MMRVNS Clinical Development Program. The assay to measure immune 
response to varicella is validated and used in other GSK Clinical Development Programs. 
Table 9 
Laboratory Assays 
Assay type 
System 
Component 
Method 
Humoral Immunity (Antibody 
determination) 
Serum 
Anti-measles Ab IgG  
Multiplex Luminex 
based Immuno Assay 
Anti-mumps Ab IgG 
Anti-rubella Ab IgG 
Anti-gE Ab IgG 
ELISA 
Abbreviations: Ab = antibody; ELISA = enzyme-linked immunosorbent assay; gE = glycoprotein E; 
IgG = immunoglobulin G 
8.1.3 
Immunological Correlates of Protection 
For measles, mumps, and rubella, there is no established correlate of protection with the 
anti-measles, -mumps, -rubella Multiplex Luminex based Immuno assay to be used in this 
study. 
The following seroresponse threshold values are proposed by GSK as endpoint defining active 
immunization offering clinical benefit: 
• 67 milli international units (mIU)/mL for anti-measles antibodies 
• 296 arbitrary units (AU)/mL for anti-mumps antibodies 
• 17 international units (IU)/mL for anti-rubella antibodies 
For varicella, there is no established correlate of protection with the anti-glycoprotein E (gE) 
enzyme-linked immunosorbent assay (ELISA) assay to be used in this study. An anti-gE 
antibody threshold of 300 mIU/mL is accepted by the Food and Drug Administration as 
endpoint defining active immunization offering clinical benefit. 
The investigator will be provided with the list of participants who do not achieve the 
pre-specified seroresponse threshold criteria in a timely manner (no later than 12 months after 
the last sampling date of the last participant enrolled). 
At the end of the study, participants who would not achieve the pre-specified seroresponse 
threshold criteria will be offered re-vaccination at the investigator’s discretion and depending 
on local recommendations, with a dose of licensed MMRV, MMR or varicella vaccine, 
depending on the antigen(s) for which the seroresponse threshold was not achieved. 

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8.2 
Safety Assessments 
8.2.1 
Pre-intervention Administration Procedures 
8.2.1.1 
Collection of Demographic Data, Medical/Vaccination History 
Demographic data such as age in years, sex, race, and ethnicity will be collected from each 
participant. Race and ethnicity will be collected as GSK seeks to have diverse clinical study 
participation (to see if the study vaccine works in all populations). Medical history should be 
collected, and it should be verified that none of exclusion criteria related to medical and 
vaccination history (see Section 5.2) are met. Prior vaccination history with respect to 
measles-, mumps-, rubella-, and varicella-containing vaccines should be obtained and 
recorded in the eCRF. 
8.2.1.2 
Checking Contraindications, Warnings, and Precautions to Intervention 
Administration 
The body temperature of each participant will be measured prior to the study intervention 
administration. GSK will provide the study center with the temperature measuring device 
which are standard devices validated by GSK’s Quality Assurance Team to ensure 
consistency in the data across study centers. If the participant has a fever (defined as 
temperature ≥38.0°C (100.4°F) regardless of the location of measurement) on the day of the 
intervention administration, or other health conditions that can be considered temporary, 
Visit 1 can be rescheduled (see Section 5.5) as long as the eligibility criteria are still met  
(see Section 5.1 and Section 5.2). 
8.2.2 
Physical Examinations 
A routine physical examination as per local standard of care will be performed for each 
participant on Day 1. 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. Refer to Section 5.5 for the list of criteria for the temporary delay of study 
intervention administration. 
8.2.3 
Clinical Safety Laboratory Tests 
No clinical safety laboratory tests are planned per protocol. Clinical safety laboratory tests 
may be performed at the investigator’s discretion if deemed necessary in case of safety 
concerns. 
8.2.4 
Safety Monitoring 
An IDMC comprising of clinical experts and a biostatistician will provide safety oversight 
during the active vaccination period, through unblinded review of the cumulative safety data. 
The first IDMC review meeting is planned after Day 43 safety follow-up of the first 

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200 vaccinated participants (approximately 50 in each group, considering pooled MMRV 
groups) is completed. A subsequent IDMC review meeting is planned during the study, after 
Day 43 safety follow-up of 400 participants is completed. The details of the review will be 
described in an IDMC charter. 
In addition to the planned IDMC meetings, monthly SRT review by GSK will occur till the 
first 200 vaccinated participants complete the Day 43 safety follow-up, to monitor cumulative, 
blinded safety data (including serious and nonserious AEs). The blinded safety data review by 
the SRT may trigger an emergency ad-hoc IDMC review. 
Solicited administration site events in terms of injection site redness, pain, and swelling; and 
solicited systemic events in terms of drowsiness, loss of appetite, fever, measles/rubella-like 
rash, varicella-like rash and other rash (not measles/rubella-like rash or varicella-like rash) 
will be collected. Unsolicited AEs, including SAEs will be encoded according to the latest 
version of the Medical Dictionary for Regulatory Activities dictionary. 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
8.3.1 
Time Period and Frequency for Collecting AE and SAEs and Other Safety 
Information 
The definitions of an AE or SAE are provided in Appendix 3. 
Collection of AEs starts on the day of the study intervention (Day 1) up to Day 43 unless the 
AE leads to study discontinuation. Collection of SAEs starts the day of the study intervention 
(Day 1) and up to study end (Day 181) unless the SAE leads to study discontinuation. The 
frequency for collection of AEs and SAEs is shown in the SoA (Section 1.3). 
8.3.2 
Method of Detecting AEs and SAEs 
The methods for detecting and recording AEs and SAEs, and the assessment of AE/SAE 
intensity, causality and outcome are provided in Appendix 3. 
The study center staff should instruct participants’ parent(s)/LAR(s) on how to report signs 
and symptoms (e.g., pain) in the individual participant. They will be instructed to report both 
specific and non-specific symptoms. 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of the participants’ parent(s)/LAR(s) is the preferred method 
to inquire about AE occurrences. Examples of the open-ended questions include “Did your 
child have any significant medical problem since the last study visit?” The study center staff 
should refrain from detailed questions, e.g., “Since the last visit, has your child experienced 
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After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up. Further 
information on follow-up procedures is provided in Appendix 3. 
8.3.3 
Regulatory Reporting Requirements for SAEs 
Once the investigator or designee becomes aware that a study participant has experienced an 
SAE, they or designated study staff must report it to IQVIA within 24 hours using an 
electronic Expedited AE Report in the eCRF. 
The investigator will provide an assessment of causality at the time of the initial report, as 
defined in the Appendix 3. New or updated information will be recorded on the originally 
completed form with all changes signed and dated by the investigator and reported to IQVIA 
within 24 hours. This is essential for meeting GSK’s legal obligations and ethical 
responsibilities for the participant’s safety and the safety of a study intervention under clinical 
investigation. 
For COVID-19-related SAEs, reports should be submitted following routine procedures for 
SAEs. 
Local regulatory requirements and GSK’s policy for the preparation of an investigator safety 
report for SUSARs must be followed. These reports will be forwarded to investigators as 
necessary. 
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. GSK 
and IQVIA will comply with country-specific requirements related to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
8.3.4 
Reporting of Suspected Unexpected Serious Adverse Reactions to the 
EudraVigilance Database 
IQVIA will keep detailed records of all AEs which are reported to IQVIA by the investigators. 
The sponsor will report electronically and without delay to EudraVigilance database all 
relevant information about any SUSAR. 
The period for the reporting of SUSARs by the sponsor to the EMA will take account of the 
seriousness of the reaction and will be as follows: 
• In the case of fatal or life-threatening SUSARs, as soon as possible and in any event no 
later than 7 days after IQVIA became aware of the reaction. 

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• In the case of non-fatal or non-life-threatening SUSARs, no later than 15 days after 
IQVIA became aware of the reaction. 
• In the case of a SUSARs which was initially considered to be non-fatal or nonlife 
threatening but which turns out to be fatal or life-threatening, as soon as possible and in 
any event no later than 7 days after IQVIA became aware of the reaction being fatal or 
life-threatening. 
Where necessary to ensure timely reporting, IQVIA may submit an initial incomplete report 
followed up by a complete report. 
8.3.5 
Annual Safety Report 
Regarding investigational medicinal products, GSK/IQVIA shall submit annually through 
Clinical Trials Information System to all Member States concerned a report on the safety of 
each investigational medicinal product used in this study. 
8.3.6 
Urgent Safety Measures and Other Relevant Safety Reporting 
Where an unexpected event is likely to seriously affect the benefit-risk balance, IQVIA and 
the investigator will take appropriate urgent safety measures to protect study participants. In 
addition, GSK/IQVIA will notify the Member States concerned, through Clinical Trials 
Information System, of the event and the measures taken. That notification will be made 
without undue delay but no later than 7 days from the date the measures have been taken. 
8.3.7 
Treatment of Adverse Events 
Any medication administered for the treatment of an SAE should be recorded in the Expedited 
AE Report. 
8.3.8 
Participant Card 
The investigator or investigator’s designee must provide the participant’s parent(s)/LAR(s) 
with a “participant card” containing information about the clinical study. The participant’s 
parent(s)/LAR(s) will be instructed to keep the participant card in their possession at all times 
throughout the study. In an emergency, this card serves to inform the responsible attending 
physician/caregiver/family member/participant’s parent(s)/LAR(s) that the participant is in a 
clinical study and that relevant information may be obtained by contacting the investigator or 
his/her backup. 
8.4 
Study Procedures During Special Circumstances 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from local 
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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 or other means of virtual contact. 
• If the eDiary device was provided to the participant’s parent(s)/LAR(s), it may be 
returned to the study center by conventional mail after the end of the relevant data 
collection period (refer to the SRM for details). If the app was provided to the 
participants’ parent(s)/LAR(s) for use on their personal device, the app can be 
disabled remotely. 
• 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. 
*Note: It is the investigator’s responsibility to identify an alternate location. The investigator 
should ensure that this alternate location meets ICH 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 the Per Protocol Set (PPS) will be determined on a case-by-case basis. Any 
impact of the above-mentioned measures on the study results will be described in the Clinical 
Study Report. 
8.5 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7 
Genetics 
Genetics are not evaluated in this study. 
8.8 
Biomarkers 
Biomarkers are not evaluated in this study. 

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8.9 
Immunogenicity Assessments 
Refer to Section 8.1 for details on immunogenicity assessments performed in this study. 
8.10 Health Economics 
Health economics parameters are not evaluated in this study. 

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9.0 STATISTICAL CONSIDERATIONS 
The SAP will be developed and finalized before First Participant First Visit. This section is a 
summary of the planned main statistical analyses of the primary and secondary 
immunogenicity endpoints. Analyses of safety are described in Section 9.3.3.2, and additional 
details will be provided in the SAP. 
9.1 
Statistical Hypotheses 
There are no statistical hypotheses in this study. All analyses are descriptive. 
9.2 
Analysis Sets 
Table 10 Analysis Sets 
Analysis set 
Description 
Enrolled (ENR) 
Participants who received a study intervention, had a blood draw before study 
intervention administration or were randomized. Note that as per Good Clinical 
Practice enrolled participants’ parent(s)/LAR(s) should have completed the informed 
consent process and participants should be eligible before initiating any study 
procedure. 
Exposed (ES) 
All participants who received a study intervention. Analysis per group is based on the 
study intervention administered. 
Per Protocol (PPS) 
All eligible participants who received a study intervention as per protocol, were not 
unblinded, had immunogenicity results pre- and post dose for at least 1 antigen, 
complied with blood draw interval between study intervention and post dose blood 
sample, without intercurrent conditions that may interfere with immunogenicity and 
without prohibited concomitant medication/vaccination. 
Abbreviations: LAR = legally acceptable representative 
Note: Intercurrent medical conditions that may lead to elimination from the PPS are defined as confirmed immunodeficiency 
condition, or development of measles, mumps, rubella or varicella illness (chicken pox) or herpes zoster in the interval 
between study intervention administration and the collection of the blood specimen for immunogenicity at Visit 3. 
9.3 
Statistical Analyses 
The SAP will be prepared and will include a more technical and detailed description of the 
statistical analyses including the supportive analyses and demography summaries. This section 
is a summary of the planned statistical analyses of the most important endpoints, i.e., the 
primary and secondary endpoints. 
9.3.1 
General Considerations 
All analyses are descriptive and therefore no statistical adjustment for interim analyses is 
required. 
9.3.2 
Primary Endpoint Analysis 
The immunogenicity primary endpoints are: 
• Anti-measles antibody geometric mean concentrations (GMCs) at Day 43 

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• Anti-mumps antibody GMCs at Day 43 
• Anti-rubella antibody GMCs at Day 43 
• Anti-gE antibody (for varicella) GMCs at Day 43 
The analysis of these immunogenicity primary endpoints will be primarily based on the PPS. 
9.3.2.1 
Within Group Assessments 
Antibody GMCs will be summarized for each MMRV antigen (i.e., measles, mumps, rubella, 
and varicella) by treatment group with their 2-sided 95% confidence interval (CI), minimum 
and maximum, derived considering log-transformed concentrations are normally distributed 
with unknown variance for antibodies against each antigen. Concentration below the assay 
cut-off will be assigned half the cut-off for the purpose of GMC computation (Table 11). 
Table 11 Assay Cut-off 
Component 
Assay cut-off 
Method 
Anti-measles Ab IgG  
29.1 mIU/mL 
Multiplex Luminex based Immuno Assay 
Anti-mumps Ab IgG 
144.3 AU/mL 
Anti-rubella Ab IgG 
1.4 IU/mL 
Anti-gE Ab IgG 
97 mIU/mL 
ELISA 
Abbreviations: Ab = antibody; AU = arbitrary unit; ELISA = enzyme-linked immunosorbent assay; 
IgG = immunoglobulin G; IU = international unit; mIU = milli international unit 
The distribution of antibody concentrations for each antigen will be displayed using reverse 
cumulative curves for the sub-cohort of initially seronegative participants. 
9.3.2.2 
Between Group Assessments 
GMC ratios of pooled MMRV group over each MMRVNS group (MMRV(H)NS, 
MM(H)RVNS and M(L)M(L)R(L)V(L)NS) will also be provided with nominal 2-sided 
95% CI. This will be obtained for each MMRV antigen (i.e., measles, mumps, rubella, and 
varicella) separately using an analysis of variance model on log-transformed antibody 
concentrations adjusted for log-transformed pre-dose antibody concentration for the antigen. 
The country will be added as a covariate. Treatment group will be included in the model and 
group contrasts with associated 2-sided 95% CI will be exponentiated to obtain treatment 
group GMC ratios for antibodies against each antigen. 
9.3.3 
Secondary Endpoints Analysis 
9.3.3.1 
Immunogenicity Secondary Endpoints 
The immunogenicity secondary endpoints are: 
• Anti-measles antibody seroresponse rate at Day 43 

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• Anti-mumps antibody seroresponse rate at Day 43 
• Anti-rubella antibody seroresponse rate at Day 43 
• Anti-gE antibody (for varicella) seroresponse rate at Day 43 
The analysis of immunogenicity will be primarily based on the PPS. 
The seroresponse rates, seropositive and seronegative, will be summarized by treatment group 
with their 2-sided 95% exact Clopper Pearson CI for antibodies against each antigen. 
Seroresponse rate for measles, mumps, and rubella is defined as the percentage of participants 
for whom the post dose antibody concentration (Day 43), as measured by the 
anti-measles, -mumps, -rubella Multiplex Luminex based Immuno assay is greater than or 
equal to the following threshold values: 
• 67 mIU/mL for anti-measles antibodies 
• 296 AU/mL for anti-mumps antibodies 
• 17 IU/mL for anti-rubella antibodies 
Seroresponse rate for varicella is defined as the percentage of participants for whom the post 
dose anti-gE antibody concentration (Day 43) is ≥300 mIU/mL as accepted by Center for 
Biologics Evaluation and Research in the context of the VNS vaccine IND (# 02775). 
• 
A seronegative participant is a participant whose antibody concentration is below the 
assay cut-off. 
• 
A seropositive participant is a participant whose antibody concentration is greater than or 
equal to the assay cut-off. 
The 2-sided 95% CI on group difference in seroresponse rate will be computed based on the 
method of Miettinen and Nurminen. 
9.3.3.2 
Safety and Reactogenicity Secondary Endpoints 
The safety analysis will be based on the Exposed Set. 
The percentage of participants reporting each solicited administration site event during the 
solicited follow-up period (Day 1-4) after vaccine administration will be tabulated per 
treatment group and over the whole vaccination course, with exact 95% CI. 
The percentage of participants reporting each solicited systemic event in terms of drowsiness 
and loss of appetite during the solicited follow-up period (Day 1-4) after vaccine 
administration will be tabulated per treatment group and over the whole vaccination course, 
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The percentage of participants reporting each solicited systemic event in terms of fever, 
measles/rubella-like rash, varicella-like rash and other rash (not measles/rubella-like rash or 
varicella-like rash) up to 42 days after vaccination administration (Days 1-43) will be 
tabulated per treatment group and over the whole vaccination course, with exact 95% CI. 
The percentage of participants reporting unsolicited AEs up to 42 days after vaccination 
administration (Days 1-43) after vaccine administration, will be tabulated with exact 95% CI. 
Percentage of participants reporting SAEs, classified by the Medical Dictionary for 
Regulatory Activities, after the vaccine administration up to study end will be tabulated with 
exact 95% CI. 
9.4 
Sequence of Analyses 
Apart from the analyses to be performed in support to the IDMC, a statistical analysis 
including safety and final immunogenicity data for all participants up to Day 43 timepoint is 
planned. 
An EoS analysis with all safety data including those obtained until the safety follow-up 
contact (Day 181) will be performed. 
Note: If there is a delay in availability of the immunogenicity data, leading to a window 
between the 2 analyses shorter than what is planned at the time of protocol writing, only one 
statistical analysis including all immunogenicity and safety data will be performed. 
All analyses are descriptive and therefore no statistical adjustment for interim analyses is 
required. 
9.5 
Sample Size Determination 
The target enrollment will be 800 participants (200 in each MMRVNS vaccine group and 
100 in each MMRV vaccine group) to obtain at least 640 evaluable participants (160 in each 
MMRVNS vaccine group and 80 in each MMRV vaccine group) for the evaluation of the 
primary objective assuming that up to 20% of the enrolled participants will not be evaluable. 
Considering 160 evaluable participants, the study will allow generating a 1.25-fold half-width 
for the 2-sided 95% CI of group GMC ratio assuming a population standard error of 0.45 in 
log10 transformed concentration. 
The randomization algorithm and handling of missing data will be detailed in the SAP. 

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10.0 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
international ethical guidelines 
• Applicable ICH GCP guidelines 
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF and informed assent form (if applicable), IB, and 
other relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by the 
investigator and reviewed and approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs, or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the study site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), European Medical 
Device Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations. 
After reading the protocol, each investigator will sign the protocol signature page and send a 
copy of the signed page to the IQVIA. The study will not start at any study site at which the 
investigator has not signed the protocol. 

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10.1.2 
Adequate Resources 
The investigator is responsible for supervising any individual or party to whom the 
investigator delegates study-related duties and functions conducted at the study site. 
If the investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the investigator/institution should ensure this individual, or 
party is qualified to perform those study-related duties and functions and should implement 
procedures to ensure the integrity of the study-related duties and functions performed and any 
data generated. 
10.1.3 
Financial Disclosure 
Investigators and sub-investigators will provide IQVIA with sufficient, accurate financial 
information as requested to allow IQVIA to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.4 
Recruitment Arrangements and Informed Consent and Assent Process 
Recruitment Arrangements 
• Potential participants will be invited to participate in this clinical study by the study 
personnel or clinical staff (including participants’ primary health physicians) in the clinic 
and/or through advertisement in appropriate resources such as, but not limited to, printed 
media, Internet, or social media. 
• Identification of potential participants can involve access to identifiable information such 
as medical records upon participants’ parent(s)/LAR(s)’ signed authorization. Clinical 
center personnel will follow national standards and obey local regulations for protection of 
sensitive patient health information. 
• It is allowed that the investigator is also participant’s physician or treating clinician. In 
such situation, there must be a separation of roles for the researcher serving as clinician 
and study-related interventions and clinical procedures. 
Informed Consent and Assent Process 
• The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participants and participants’ parent(s)/LAR(s) and 
answer all questions regarding the study. 
• Potential participants and their parent(s)/LAR(s) must be informed that their participation 
is voluntary. They or their parent(s)/LAR(s) will be required to physically or digitally sign 
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21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, privacy and data protection requirements, where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that physical or digital informed consent was 
obtained before the participant was enrolled in the study and the date the physical or 
digital consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A physical or digital copy of the ICF(s) must be provided to the participant and/or their 
parent(s)/LAR(s). 
• The investigator must obtain assent from the minor participant in addition to the consent 
provided by the participants’ parent(s)/LAR(s) when a minor can assent to participate in a 
study. The investigator is also accountable for determining a minor’s capacity to assent to 
participation in a research study according to the local laws and regulations. 
10.1.5 
Data Protection 
• Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets that are transferred to GSK and/or IQVIA will contain the identifier 
only; participant names or any information which would make the participant identifiable 
will not be transferred. 
• GSK and IQVIA will ensure protection of the personal data of the investigator and site 
staff which is collected within the framework of and for the purpose of the study. 
• The participants’ parent(s)/LAR(s) must be informed that their child’s study-related data 
will be used by GSK and IQVIA in accordance with local data protection law. The level of 
disclosure must also be explained to the participants’ parent(s)/LAR(s) and their child’s 
data to be used as described in the informed consent. 
• The participants and participants’ parent(s)/LAR(s) must be informed that participant’s 
medical records may be examined by Clinical Quality Assurance auditors or other 
authorized personnel appointed by GSK and IQVIA, by appropriate IRB/IEC members, 
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• The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. GSK 
and/or IQVIA and/or institutions working with GSK and IQVIA for the purposes of this 
study are contractually bound to protect participant coded data. GSK and IQVIA will 
protect participant coded data and will only share it as described in the ICF and informed 
assent form (if applicable). 
10.1.6 
Study Administrative Structure 
Table 12 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 
IQVIA 
Biostatistics, Medical Writing 
IQVIA 
10.1.7 
Safety Data Review and Data Monitoring Committee 
Besides safety monitoring by blinded Study/Center Monitors (see the definition in 
Appendix 4), an IDMC comprising of clinical experts and an independent biostatistician will 
provide safety oversight during the active vaccination period, through unblinded review of the 
cumulative safety data. 
The first IDMC review meeting is planned after Day 43 safety follow-up of the first 
200 vaccinated participants (approximately 50 in each group, considering pooled MMRV 
groups) is completed. A subsequent IDMC review meeting is planned during the study, after 
Day 43 safety follow-up of 400 participants is completed. The details of the review will be 
described in an IDMC charter. 
In addition to the planned IDMC meetings, monthly SRT review by GSK will occur till the 
first 200 vaccinated participants complete the Day 43 safety follow-up, to monitor cumulative, 
blinded safety data (including serious and nonserious AEs). The blinded safety data review by 
the SRT may trigger an emergency ad-hoc IDMC review. 

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10.1.8 
Dissemination of Clinical Study Data 
The key design elements of this protocol and results summaries will be posted on 
ClinicalTrials.gov, GSK Clinical Study Register and Eudract.Ema.Europa.Eu in compliance 
with applicable regulations/GSK policy. GSK will aim to register protocols 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’ parent(s)/LAR(s), as appropriate. 
GSK will provide the investigator with the randomization codes for their site 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 to ensure the data provided by study participants 
are used to maximum effect in the creation of knowledge and understanding. 
Publication Policy 
GSK aims to submit for publication the results of the study in searchable, peer reviewed 
scientific literature within 18 months from LPLV and follow authorship and other guidance 
from the International Committee of Medical Journal Editors. 
10.1.9 
Data Quality Assurance 
• The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (see Appendix 4 for definitions 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 fulfill the 
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• All participant data related to the study will be recorded on printed or eCRF unless 
transmitted to GSK/IQVIA 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 Appendix 4 for the definition of source documents) that supports information entered 
in the eCRF. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection. 
• IQVIA is responsible for the data management of this study including quality checking of 
the source data (see Appendix 4 for the 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. 
• Details of study monitoring, including action required due to COVID-19, will be included 
in a separate Study Monitoring Plan and/or other documents pertinent to study monitoring. 
• Quality tolerance limits will be predefined to identify systematic issues that can impact 
participant safety and/or the reliability of study results. 
• 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 
Clinical Study Report/equivalent summary unless local/country-specific 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. 
10.1.10 
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 
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• 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 Appendix 4. 
10.1.11 
Study and Study Center Start and Closure 
The first act of recruitment is defined as First Participant First Visit at a country level. 
GSK/IQVIA reserves the right to close the study center or terminate the study at any time for 
any reason, provided there is sufficient notice given to account for all participants safe exit 
from study. 
Regular closure of study centers will occur upon study completion. A study center is 
considered closed when all required data/documents and study supplies have been collected 
and a study center closure visit has been performed. 
The investigator may initiate study center closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by GSK/IQVIA or investigator may include but 
are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, GSK’s/IQVIA’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, IQVIA shall promptly inform the 
investigators, the IRBs/IECs, and the regulatory authorities of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The investigator shall 
promptly inform the participants and should assure appropriate participant therapy and/or 
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10.2 Appendix 2: Clinical Laboratory Tests 
gE Enzyme-linked Immunosorbent Assay 
Anti-gE ELISA is a 2-step ELISA based on the antibody and antigen interaction, which allows 
the detection and the quantification of specific immunoglobulin G (IgG) antibodies directed 
against gE in tested serum samples. 
Briefly, diluted serum samples are added onto a 96-polystyrene-well microplate pre-coated 
with gE. Then goat antibodies directed against human IgG antibodies and conjugated to 
horseradish peroxidase (a-IgG-HRP) are added and will bind to anti-gE IgG if present. After a 
washing step, the addition of a chromogen-substrate solution specific for HRP will provide 
means of detecting the anti-gE specific for the pre-coated antigen. The HRP catalyzes an 
enzymatic reaction which is stopped by the addition of sulfuric acid, resulting in a color 
change from blue to yellow. 
The optical density recorded is proportional to the concentration of the anti-gE antibodies 
present in the serum sample. Antibody titer is expressed in mIU/mL. 
Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Multiplex Luminex based Immuno Assay 
In the assay, inactivated native viruses from measles, mumps, rubella, and varicella are 
coupled to their assigned Luminex MicroPlex microsphere type. Each microsphere type has its 
own distinct fluorescent dye that can be recognized by excitation with a red laser. The red 
laser classifies the microsphere type and determines the corresponding assigned virus that is 
being detected. The 4 microsphere types are incubated with human serum. Following this, the 
microspheres are washed to remove excess sera and incubated with R-Phycoerythrin 
conjugated goat anti-human IgG antibody. The fluorescent signal from the PE-labeled 
conjugate, recognized by excitation with a green laser, is proportional to the anti-virus IgG 
concentration in the serum sample tested. IgG concentrations are derived from the MMRV 
Secondary Standard curve, which is made of pooled sera with positive reactivity to all 
4 viruses and is aligned to the World Health Organization International reference standards for 
measles (National Institute for Biological Standards and Control [NIBSC] reference 
# 97/648), rubella (NIBSC reference # RUBI-1-94) and varicella zoster virus (NIBSC 
reference# W1044), and to NIBSC QC Reagent for mumps (NIBSC reference # 15/B664). 
The MMRV Secondary Standard is 2-fold serially diluted in duplicate to create a 10-point 
(STD1 to STD10) standard curve for each of the MMRV antigens. Standard curve for each 
virus is calculated using a 3 Parameter Logistic curve fit. Results are expressed in mIU/mL for 
measles and varicella, AU/mL for mumps, and IU/mL for rubella. Samples are quantified at 
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10.3 Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention 
10.3.1 
Definition of 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. 
10.3.1.1 
Events Meeting the AE Definition 
• Significant or unexpected worsening or exacerbation of the condition/indication under 
study. 
• Exacerbation of a chronic or intermittent preexisting 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 
(i.e., invasive procedures, modification of participant’s previous therapeutic regimen). 
• 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 10.3.3. 
• All other AEs will be recorded as UNSOLICITED AEs. 
• The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. 
 
10.3.1.2 
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). 

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• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
• Preexisting conditions or signs and/or symptoms present in a participant before the first 
dose of study intervention. These events will be recorded in the medical history section 
of the eCRF. 
• Hospitalization for elective treatment of a preexisting 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. 
10.3.2 
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, if it were more severe. 
c. Requires inpatient 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 fulfills any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalization” occurred or was necessary, the AE should be considered serious. 
d. Results in persistent or significant disability/incapacity 
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) that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. Other situations 
Medical or scientific judgment 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 
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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. 
10.3.3 
Solicited Events 
a. Solicited administration site events 
The following administration site events will be solicited: 
Table 13 Solicited Administration Site Events 
Participants 4-6 years of age 
Injection site redness 
Pain 
Swelling 
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 14 Solicited Systemic Events 
Participants 4 to 6 years of age 
Drowsiness 
Loss of appetite 
Fever 
Measles/rubella-like rash 
Varicella-like rash 
Other rash (not measles/rubella-like rash or varicella-like rash) 
Note: Participants’ parent(s)/legally acceptable representative(s) will be instructed to measure and record the axillary 
temperature in the evening. If additional temperature measurements are taken at other times of the day, participants’ parent(s)/ 
legally acceptable representative(s) will be instructed to record the highest temperature in the electronic diary/application. 
10.3.4 
Unsolicited Adverse Events 
An unsolicited AE is an AE that was either not included in the list of solicited events or could 
be included in the list of solicited events but with an onset outside the specified period of 
follow-up for solicited events. Unsolicited AEs must have been communicated by a 
participant’s parent(s)/LAR(s) who has signed the informed consent. Unsolicited AEs include 
both serious and nonserious AEs. 
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 
participant’s parent(s)/LAR(s) will be instructed to contact the site as soon as possible to 

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report medically attended event(s), as well as any events that, though not medically attended, 
are of participant’s parent(s)/LAR(s)’ concern. 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 or perceived as a concern by the participant’s 
parent(s)/LAR(s) will be collected during an interview with the participant’s parent(s)/LAR(s) 
and by review of available medical records at the next visit. 
10.3.5 
Coronavirus Disease 2019 Cases 
Diagnosis of COVID-19 should be made in accordance with the World Health Organization 
case definition. Cases should be categorized as AEs (unsolicited or AEs leading to 
withdrawal) or SAEs, 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. 
10.3.6 
Assessment of Intensity 
The intensity of the following solicited AEs will be assessed as described in Table 15. 
Table 15 Intensity Scales for Solicited Symptoms in Children (4 to 6 Years of Age) 
Children (4 to 6 years of age) 
Adverse Event 
Intensity Grade 
Parameter 
Pain at injection site 
0 
None 
1 
Mild: Minor reaction to touch 
2 
Moderate: Cries/protests on touch 
3 
Severe: Cries when limb is moved/spontaneously painful 
Redness at injection site 
Greatest surface diameter in mm 
Swelling at injection site 
Greatest surface diameter in mm 
Fever* 
Temperature in °C/°F 
Measles/rubella-like rash** 
Number of lesions 
Varicella-like rash*** 
Number of lesions 
Other rash (not 
measles/rubella-like rash or 
varicella-like rash) 
0 
None 
1 
Mild: Rash which is easily tolerated by the child, causing minimal 
discomfort and not interfering with everyday activities 
2 
Moderate: Rash which is sufficiently discomforting to interfere with 
normal everyday activities 
3 
Severe: Rash which prevents normal, everyday activities (in a young 
child, such an adverse events would, for example, prevent attendance at 
school/day care and would cause the parent(s)/legally authorized 
representative(s) to seek medical advice) 
Drowsiness 
 
0 
Behavior as usual 
1 
Mild: Drowsiness easily tolerated 
2 
Moderate: Drowsiness that interferes with normal activity 
3 
Severe: Drowsiness that prevents normal activity 
Loss of appetite 
 
0 
Appetite as usual 
1 
Mild: Eating less than usual/no effect on normal activity 
2 
Moderate: Eating less than usual/interferes with normal activity 
3 
Severe: Not eating at all 
*Fever is defined as temperature ≥38.0°C (100.4°F) by any route. The preferred location for measuring temperature will be 
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**A measles/rubella-like rash manifests as presence of macules, discolored small patches or spots of the skin, neither elevated 
nor depressed below the skin's surface and/or papules, raised bumps on the skin usually <1 cm in diameter. 
***A typical varicella-like rash manifests as a rash/lesion that may appear within 2 weeks (or sometimes later) after the 
varicella vaccination. Lesions may contain spots, bumps, blisters, or crusts. 
Refer to the SRM for detailed guidelines about the rashes. 
The maximum intensity of administration site redness/swelling/measles/rubella-like 
rash/varicella-like rash/fever/will be scored as follows: 
Intensity 
Grade 
Redness/swelling 
Measles/rubella-like rash and 
varicella-like rash* 
Fever** 
0 
None 
None 
<38.0°C (100.4°F) 
1 
>0 - ≤5 mm 
1-25 lesions 
≥38.0°C (100.4°F) - ≤39.0°C (102.2°F) 
2 
>5 - ≤20 mm 
26-50 lesions 
>39.0°C (102.2°F) - ≤39.5°C (103.1°F) 
3 
>20mm 
≥51 lesions 
>39.5°C. (103.1°F) 
*Including injection site varicella-like rash 
**Temperature will be analyzed in 0.5°C increments from ≥38.0°C (100.4°F). 
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 judgment. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE that is sufficiently discomforting to interfere with normal 
everyday activities. 
3 (severe) 
= 
An AE that prevents normal everyday activities. Such an AE 
would, for example, prevent attendance at a childcare facility and 
would cause the parent(s)/LAR(s) to seek medical advice. 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. 
Grade 3 is a category used for rating the intensity of an event; and both AEs and SAEs 
can be assessed as Grade 3. An event is defined as “serious” when it meets one of the 
predefined outcomes as described above. 
10.3.7 
Assessment of Causality 
The investigator must assess the relationship between study intervention and the occurrence of 
each unsolicited AE/SAE using clinical judgment. 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 

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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 the 
Summary of Product Characteristics 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 as “serious” (see Section 10.3.2), 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 IQVIA. However, it is very important to record 
an assessment of causality for every event before submitting the Expedited AE Report to 
IQVIA. 

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The causality assessment is one 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. 
10.3.8 
Medically Attended Visits 
For each solicited and unsolicited AE the participant experiences, the participant’s 
parent(s)/LAR(s) will be asked if the participant 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 in the participant’s 
eDiary (for solicited AEs) and in the participant’s eCRF as part of normal AE reporting  
(for unsolicited AEs). Medical attention received for SAEs will have to be reported using the 
normal AE reporting process in the eCRF. 
10.3.9 
Assessment of Outcomes 
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• Recovered/resolved 
• Recovering/resolving 
• Not recovered/not resolved 
• Recovered with sequelae/resolved with sequelae 
• Fatal (SAEs only). 
10.3.10 
Reporting, Follow-up, and Assessment of AEs 
Recording AEs and SAEs 
• All AEs and SAEs should be recorded into the appropriate section of the eCRF, 
irrespective of intensity or whether or not they are considered intervention related. 
• The participants’ parent(s)/LAR(s) will be instructed to contact the investigator 
immediately should the participants manifest any signs or symptoms they perceive as 
serious. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
participant’s medical records to either the sponsor or IQVIA instead of appropriately 
completing the eCRF. However, there may be instances when copies of medical records 
for certain cases are requested by the sponsor or IQVIA. In this instance, all participant 
identifiers will be blinded on the copies of the medical records prior to submission to the 

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sponsor or IQVIA. 
• 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 and not the individual signs/symptoms. 
 
The Use of eDiary/Personal Electronic Device App 
An eDiary will be used in this study to capture solicited administration site or systemic 
events. The participants’ parent(s)/LAR(s) should be trained on how and when to complete 
the eDiary/enter information into the app. 
Anyone who measures administration site or systemic events and who will record the event 
in the eDiary/app should be trained on using the eDiary/app. This training must be 
documented in the participant’s source documents. If any individual other than the 
participant’s parent(s)/LAR(s) is making entries in the eDiary/app, their identity must be 
documented in the eDiary/app/participant’s source documents. 
 
Time Period for Collecting and Recording of AEs and SAEs 
All solicited administration site events that occur during 4 days (Day 1 to Day 4), and 
solicited systemic events that occur during 4 days (Day 1 to Day 4; for drowsiness and loss 
of appetite) or 43 days (Day 1 to Day 43; other solicited systemic events) following 
administration of the study intervention, must be recorded into the eDiary/personal 
electronic device app, irrespective of intensity. Unsolicited events occurring from Day 1 to 
Day 43 and SAEs occurring up the end of the study should be recorded into the appropriate 
section of the eCRF, irrespective of intensity or whether or not they are considered 
vaccination related. 
 
Follow-up of AEs and SAEs 
After the initial AE/SAE or any other event of interest for the study, the investigator is 
required to proactively follow each participant at subsequent visits/contacts. All SAEs will 
be followed until the event is resolved, stabilized, or otherwise explained or the participant 
is lost to follow-up. 
Other nonserious AEs must be followed until the last contact or until the participant is lost 
to follow-up. 

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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 the participant dies during participation in the study or during a recognized follow-up 
period, IQVIA will be provided with any available post-mortem findings, including 
histopathology. 
Follow-up After the Participant is Discharged from the Study 
The investigator will provide any new or updated relevant information on previously 
reported SAE to IQVIA using electronic Expedited AE Report as applicable. 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 AE or 
SAE as fully as possible. 
Updating of SAE Information After Removal of Write Access to the Participant’s 
eCRF 
When additional SAE information is received after removal of write access to the 
participant’s eCRF, 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 IQVIA as described within the timeframes specified in Section 8.3.1. 
 
Events Requiring Expedited Reporting to IQVIA: 
SAE(s) throughout the study 
• 
Once the investigator or designee becomes aware that study participant(s) have 
experienced an SAE, the investigator or designated study staff must complete 
information in the electronic Expedited AE Report in the eCRF WITHIN 24 HOURS. 
The report will always be completed as thoroughly as possible with all available details 
of the event. 
• 
Even if the investigator does not have all information regarding an SAE, the report 
should still be completed within 24 hours. Once additional relevant information is 
received, the report should be updated WITHIN 24 HOURS. The investigator will 
always provide an assessment of causality at the time of the initial report. 
• 
Refer to Section 8.3.1 for the details on timeframes for reporting of SAEs. 

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SAE Reporting to IQVIA via an Electronic Data Capture Tool 
• The primary mechanism for reporting an SAE to IQVIA 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. 
• The study center staff will enter the SAE 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) 
or to the Medical Monitor by phone. 
• Contacts of the Medical Monitor for SAE reporting can be found in the SRM. 
 
Backup SAE Reporting to IQVIA via Paper (in Case of EDC Failure) 
• Fax transmission of the SAE paper Expedited AE Report is the preferred method to 
transmit this information to the Medical Monitor. 
• In rare circumstances and in the absence of Fax equipment, notification by phone is 
acceptable with a copy of the Expedited AE Report sent by overnight mail or courier 
service. 
• Initial notification via phone does not replace the need for the investigator to complete 
and sign the Expedited AE Report within the designated reporting timeframes. 
• Contacts of the Medical Monitor for SAE reporting can be found in the SRM. 
 

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10.4 Appendix 4: Abbreviations and Definitions 
Abbreviation 
Definition 
ACIP 
Advisory Committee on Immunization Practices 
AE 
Adverse Event 
App 
Application 
AU 
Arbitrary unit 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
COVID-19 
Coronavirus disease 2019  
CSR 
Clinical study report 
DTPa 
Diphtheria-tetanus-acellular pertussis 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture Tool 
eDiary 
Electronic diary 
ELISA 
Enzyme-linked immunosorbent assay 
EoS 
End of study 
EU 
European Union 
GCP 
Good Clinical Practice 
gE 
Glycoprotein E 
GMC 
Geometric mean concentration 
GSK 
GlaxoSmithKline Biologicals SA 
HRP 
Horseradish peroxidase 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ID 
Participant identification number 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IRB 
Institutional Review Board 
IRT 
Interactive Response Tool 
IU 
International unit 
IVRS 
Interactive Voice Response System 

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Abbreviation 
Definition 
IWRS 
Interactive Web Response System 
LAR 
Legally acceptable representative 
LPLV 
Last Participant Last Visit 
mIU 
Milli international unit 
MMRVNS 
Measles, mumps, rubella, and varicella vaccine (investigational 
vaccine) 
MMRV 
Measles, mumps, rubella, and varicella vaccine (comparator 
vaccine) 
NIBSC 
National Institute for Biological Standards and Control  
PPS 
Per Protocol Set 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Activities 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
US 
United States (of America) 
VZV 
Varicella zoster virus 
WHO 
World Health Organization 
 
Glossary of Terms 
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 an SAE. In a single-blind 
study, the investigator(s) and/or their staff are aware of the 
intervention assignment but the participant/parent(s)/LAR(s) is not. 
Caregiver: 
A caregiver is someone who 
• lives in the close surroundings of a participant and has a 
continuous caring role or 

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• has substantial periods of contact with a participant and is 
engaged in his/her daily health care (e.g., a relative of the 
participant). 
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. 
Child in care: 
A child who has been placed under the control or protection of an 
agency, organization, institution or entity by the courts, the 
government or a government body, acting in accordance with 
powers conferred on them by law or regulation. The definition of a 
child in care can include a child cared for by foster parents or living 
in a care home or institution, provided that the arrangement falls 
within the definition above. The definition of a child in care does not 
include a child who is adopted or has an appointed legal 
guardian/LAR(s). 
Combination 
product: 
Combination product comprises any combination of 
a. drug 
b. device 
c. 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 parent(s)’/LAR(s)’ agreement to 
participate in a clinical study following completion of the informed 
consent process. Potential participants who are screened for 
determining eligibility for the study, but do not participate in the 
study, are not considered enrolled. 
Essential documents: Documents which individually and collectively permit evaluation of 
the conduct of a study and the quality of the data produced. 
Evaluable: 
Meeting all eligibility criteria, complying with the procedures 
defined in the protocol, and, therefore, included in the per protocol 
analysis. 

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Immunological 
correlate of 
protection: 
A correlate of risk that has been validated to predict a certain level 
of protection from the targeted endpoint. 
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. 
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. 
Legally acceptable 
representative: 
An individual or juridical or other body authorized under applicable 
law to consent, on behalf of a prospective participant, to the 
participant's participation in the clinical trial. The terms legal 
representative and legally authorized representative are used in some 
settings. 
Medical Monitor
 
 
IQVIA’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: 
An individual whose parent(s)/LAR(s) has been contacted to 
participate or participates in the clinical trial, either as a recipient of 
the vaccine(s)/product or as a control. 
Participant ID: 
A unique identification number assigned to each participant who 
consents to participate in the study. 

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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. For this study, the 
team is responsible for reviewing observed safety concerns based on 
blinded 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 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 IQVIA (see the study administrative 
structure in Appendix 1 [Table 12]) 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. 

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Unsolicited event: 
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. 
 
 

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11.0 REFERENCES 
Advisory Committee on Immunization Practices (ACIP). Prevention of varicella: 
recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for 
Disease Control, Atlanta, GA. MMWR. 2007;56 (No. RR-4). 
CDC Morbidity and Mortality Weekly Report (MMWR). Use of Combination Measles, 
Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on 
Immunization Practices (ACIP). 2010; 59(RR03):1-12. Accessed 23 May 2022 
 
 
 

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Signature of Investigator 
PROTOCOL TITLE: A Phase II, single-blind, randomized, controlled study to evaluate the 
immunogenicity and safety of a measles, mumps, rubella, varicella vaccine compared with 
ProQuad, administered in healthy children 4 to 6 years of age 
PROTOCOL NO: 
217715 (MMRVNS 20-001) 
Date of protocol:  
15 March 2023 
This protocol is a confidential communication of GSK. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from the GSK. 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy to IQVIA. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
Signature of Investigator:  
 __________________________  
Date: ________________ 
Printed Name:  
 
___________________________ 
Investigator Title:  
 
___________________________ 
 
Name/Address of Center:  
 
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________