A Phase III, Open-label, Randomized, Controlled, Multi-country Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co-administered With Herpes Zoster Recombinant Subunit (HZ/su) Vaccine in Adults Aged 50 Years and Older
Phase: PHASE3
Conditions: Respiratory Syncytial Viruses, Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

 
 
TITLE PAGE 
Protocol Title:  
A Phase III, open-label, randomized, controlled, multi-country study to evaluate the immune response, 
safety and reactogenicity of RSVPreF3 OA investigational vaccine when co-administered with Herpes 
Zoster recombinant subunit (HZ/su) vaccine in adults aged 50 years and older. 
Protocol Number: 219331 
Compound: RSVPreF3 OA 
Study Phase: III 
Sponsor: GlaxoSmithKline Biologicals S.A. 
Legal Registered Address: Rue De L’Institut 89, 1330 Rixensart, Belgium 
Date of Original Protocol: 17 April 2023
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PROTOCOL SUMMARY OF CHANGES TABLE 
 
DOCUMENT HISTORY 
 
 
Document 
Date 
Substantial 
Region 
Original Protocol v2.0 
17-April-2023 
No 
Global 
Original Protocol 
21-March-2023 
- 
- 
 
Original Protocol v2.0 (17-April-2023) 
 
This protocol update 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 Protocol Update: 
 
The Original Protocol is updated to version 2.0 to add the Day 8 remote contact visit to the 
tables describing the timeframe for collecting and reporting safety information and to correct 
the participant age range in one instance of this document.   
 
(Added text is bold italic, deleted text is strikethrough) 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities 
Edited footnote of 
Table 1 Schedule of Activities for 
the Co-administration Group 11At 
Visits 1 and 3 (Co-ad group), 
pregnancy information must be 
recorded prior to study 
intervention administration. 
Pregnancies will be followed as 
described in Section 10.4.3. 
and Table 2 Schedule of Activities 
for the Control Group 12At Visits 1, 
2, and 3 (Control group), 
pregnancy information must be 
recorded prior to study 
intervention administration. 
Pregnancies will be followed as 
described in Section 10.4.3. 
Clarification 
8.3.1 Time Period and 
Frequency for Collecting 
AE, SAE, and Other 
Safety Information 
 
Added Day 8 visit column to  
Table 13 Timeframes for 
Collecting and Reporting of Safety 
Information for the Co-ad Group, 
and Table 14 Timeframes for 
Collecting and Reporting of Safety 
Information for the Control Group 
Clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
 
Edited Recording of pregnancies 
row in Tables 13 and 14 to show 
visits in which pregnancy 
information is recorded. 
9.3.1 Primary 
Endpoints/Estimands 
Analysis 
Deleted text: 
*The model will include the 
treatment group and the age 
category (age at vaccination: 50 to 
59, 60 to 69, or ≥70 to 79) as fixed 
effects, and the pre-vaccination 
log10-transformed titer as 
covariate. 
Correction 
Summary of Changes 
Summary of Changes table was 
added to document updates to 
Original Protocol. 
Version control 
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PROTOCOL INVESTIGATOR AGREEMENT 
I agree: 
• To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• To assume responsibility for the proper conduct of the study at this site. 
• That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• That I will comply with the terms of the site agreement. 
• To ensure that all individuals assisting me with the study are adequately informed 
about the GSK study intervention and other study-related duties and functions as 
described in the protocol. 
• To supervise any individual or party to whom I have delegated study-related duties and 
functions conducted at the study site. 
• To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality Assurance 
procedure manual. 
• To ensure that no clinical samples (including blood and serum samples) are retained 
onsite or elsewhere without the approval of GSK and the express written informed 
consent of the participant. 
• To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 
Hence, I: 
• Agree to supply GSK with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children). 
• Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
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• Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 
 
Investigator name:  
__________________________________________ 
 
Signature: 
 
 
__________________________________________ 
 
Date:  
 
 
__________________________________________ 
 
 
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TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY ........................................................................................ 13
1.1
Synopsis .......................................................................................................... 13
1.2
Schema ............................................................................................................ 16
1.3
Schedule of Activities .................................................................................... 17
2.0 
INTRODUCTION ..................................................................................................... 25
2.1
Study Rationale .............................................................................................. 25
2.2
Background .................................................................................................... 25
2.3
Benefit/Risk Assessment................................................................................ 26
2.3.1 
Risk Assessment................................................................................ 26
2.3.2 
Benefit Assessment ........................................................................... 28
2.3.3 
Overall Benefit Risk Conclusion ...................................................... 29
3.0 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................... 30
4.0 
STUDY DESIGN ....................................................................................................... 32
4.1
Overall Design ................................................................................................ 32
4.1.1 
Overview of Recruitment Plan .......................................................... 32
4.1.2 
Enrollment Rules ............................................................................... 33
4.2
Scientific Rationale for Study Design .......................................................... 33
4.3
Justification for Dose of RSVPreF3 OA Investigational Vaccine ............. 34
4.4
End of Study Definition ................................................................................. 34
4.5
Study Holding Rules ...................................................................................... 35
4.6
Participant Input into Design ....................................................................... 37
5.0 
STUDY POPULATION ............................................................................................ 38
5.1
Inclusion Criteria ........................................................................................... 38
5.2
Exclusion Criteria .......................................................................................... 39
5.2.1
Medical conditions ............................................................................ 39
5.2.2
Prior and Concomitant Therapy ........................................................ 40
5.2.3
Prior/Concurrent clinical study experience ....................................... 41
5.2.4
Other exclusions ................................................................................ 41
5.3
Lifestyle Considerations ................................................................................ 41
5.4
Caregiver Support ......................................................................................... 41
5.5
Screen Failures ............................................................................................... 42
5.6
Criteria for Temporarily Delaying .............................................................. 42
6.0 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .................... 44
6.1
Study Intervention(s) Administered ............................................................ 44
6.1.1 
Medical Devices ................................................................................ 45
6.2
Preparation, Handling, Storage, and Accountability ................................. 45
6.3
Measures to Minimize Bias: Randomization and Blinding ....................... 45
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6.3.1 
Participation Identification ................................................................ 45 
6.3.2 
Randomization to Study Intervention ............................................... 46 
6.3.3 
Intervention Allocation to the Participant ......................................... 46 
6.3.4 
Allocation of Participants to Assay Subsets...................................... 46 
6.3.5 
Blinding and Unblinding ................................................................... 46 
6.4 
Study Intervention Compliance ................................................................... 47 
6.5 
Dose Modification .......................................................................................... 47 
6.6 
Treatment of Overdose ................................................................................. 47 
6.7 
Concomitant Therapy ................................................................................... 47 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 49 
7.1 
Discontinuation of Study Intervention ........................................................ 49 
7.1.1 
Contraindications to Subsequent Study Intervention 
Administration................................................................................... 50 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................... 50 
7.3 
Lost to Follow-up ........................................................................................... 51 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 53 
8.1 
Immunogenicity Assessments ....................................................................... 54 
8.1.1 
Biological Samples............................................................................ 54 
8.1.2 
Laboratory Assays ............................................................................. 55 
8.1.3 
Immunological Read-Outs ................................................................ 56 
8.1.4 
Immunological Correlates of Protection ........................................... 56 
8.2 
Safety Assessments ........................................................................................ 56 
8.2.1 
Pre-Vaccination Procedures .............................................................. 57 
8.2.2 
Safety Contact at 6 Months Post-Last Vaccination ........................... 58 
8.2.3 
Clinical Safety Laboratory Tests ....................................................... 59 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 59 
8.3.1 
Time Period and Frequency for Collecting AE, SAE, and 
Other Safety Information .................................................................. 59 
8.3.2 
Method of Detecting AEs, SAEs, Pregnancies, and Other 
Events ................................................................................................ 65 
8.3.3 
Follow-up of AEs, SAEs, pIMDs, and Pregnancies ......................... 65 
8.3.4 
Regulatory Reporting Requirements for SAEs, pIMDs, 
Pregnancies, and Other Events .......................................................... 65 
8.3.5 
Treatment of Adverse Events ............................................................ 66 
8.3.6 
Medical Device Deficiencies ............................................................ 66 
8.3.7 
Pregnancy .......................................................................................... 68 
8.3.8 
Adverse Events of Special Interest ................................................... 68 
8.4 
Participant Card ............................................................................................ 69 
8.5 
Pharmacokinetics .......................................................................................... 69 
8.6 
Pharmacodynamics ....................................................................................... 69 
8.7 
Genetics .......................................................................................................... 69 
8.8 
Biomarkers ..................................................................................................... 69 
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8.9 
Immunogenicity Assessments ....................................................................... 69 
8.10 
Health Economics .......................................................................................... 69 
9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 70 
9.1 
Statistical Hypotheses .................................................................................... 70 
9.2 
Populations for Analysis ............................................................................... 71 
9.2.1 
Criteria for Elimination ..................................................................... 72 
9.3 
Statistical Analyses ........................................................................................ 72 
9.3.1 
Primary Endpoints/Estimands Analysis ............................................ 72 
9.3.2 
Secondary Endpoints/Estimands Analysis ........................................ 74 
9.4 
Interim Analysis ............................................................................................. 75 
9.4.1 
Sequence of Analyses ....................................................................... 75 
9.5 
Sample Size Determination ........................................................................... 76 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 77 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 77 
10.1.1 
Regulatory and Ethical Considerations ............................................. 77 
10.1.2 
Adequate Resources .......................................................................... 78 
10.1.3 
Financial Disclosure .......................................................................... 78 
10.1.4 
Recruitment Arrangements and Informed Consent Process ............. 78 
10.1.5 
Data Protection .................................................................................. 79 
10.1.6 
Safety Review Team Structure .......................................................... 80 
10.1.7 
Dissemination of Clinical Study Data ............................................... 80 
10.1.8 
Data Quality Assurance ..................................................................... 80 
10.1.9 
Source Documents ............................................................................ 81 
10.1.10 Study and Site Start and Closure ....................................................... 82 
10.1.11 Publication Policy ............................................................................. 83 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 84 
10.3 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention .................................................................................................... 85 
10.3.1 
Definition of AE ................................................................................ 85 
10.3.2 
Definition of SAE and Serious Adverse Device Effect 
(SADE) .............................................................................................. 88 
10.3.3 
Adverse Events of Special Interest ................................................... 89 
10.3.4 
Clinical Laboratory Parameters and Other Abnormal 
Assessments Qualifying as AEs or SAEs ....................................... 100 
10.3.5 
Recording and Follow-Up of AE, SAE, pIMD, Pregnancy, 
and Device Deficiencies .................................................................. 100 
10.3.6 
Reporting of SAEs, pIMDs, Pregnancy, and Medical 
Device SAEs ................................................................................... 106 
10.4 
Appendix 4: Contraceptive and Barrier Guidance and 
Collection of Pregnancy Information ........................................................ 108 
10.4.1 
Definitions ....................................................................................... 108 
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10.4.2 
Contraception Guidance .................................................................. 108 
10.4.3 
Collection of Pregnancy Information .............................................. 109 
11.0 
APPENDIX 5: ABBREVIATIONS AND GLOSSARY OF TERMS ................. 111 
12.0 
REFERENCES ........................................................................................................ 116 
 
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LIST OF FIGURES 
Figure 1 
Study Schema ................................................................................................... 16 
Figure 2 
Evaluations Based on 27 Participants in the Co-administration Group. Risk    
Assessment Curve Based on the Proposed Safety Holding Rules ................... 37 
 
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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title:  
A Phase III, open-label, randomized, controlled, multi-country study to evaluate the immune 
response, safety and reactogenicity of RSVPreF3 OA investigational vaccine when 
co-administered with Herpes Zoster recombinant subunit (HZ/su) vaccine in adults aged 
50 years and older. 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial 
virus (RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) 
adjuvanted with liposome-based AS01E system, against RSV-associated (subtypes A and B) 
disease. In a large phase III vaccine clinical trial in adults aged 60 years and above, the 
vaccine candidate demonstrated overall vaccine efficacy of 82.6% (96.95% Confidence 
Interval [CI], 57.9–94.1) against RSV lower respiratory tract disease (RSV-LRTD). The 
vaccine was well tolerated with a favorable safety profile. The study is still ongoing to assess 
other endpoints. GSK is aiming to expand the label indication to include a population of 50 to 
59 years of age. A study to evaluate immune response and safety of RSVPreF3 OA 
investigational vaccine in adults 50 to 59 YOA, versus adults ≥60 YOA is ongoing. 
GSK’s herpes zoster (HZ) vaccine is a non-live, recombinant subunit (su) vaccine (Shingrix, 
hereby referred to as HZ/su vaccine) and consists of the varicella zoster virus (VZV) 
glycoprotein E (gE) as an active ingredient, together with the liposome-based adjuvant system 
AS01B. Earlier studies have established that HZ/su vaccine is highly efficacious and induces 
strong cellular and humoral immune responses with a clinically acceptable safety profile in 
adults ≥50 YOA.  
The HZ/su vaccine is indicated for use in adults ≥50 YOA in USA, Canada, and UK 
(proposed study countries). Since both the vaccines will be indicated for use in individuals of 
overlapping age groups, evaluation of the co-administration of the RSVPreF3 OA and HZ/su 
vaccines is of interest.  
The present study will assess the immunogenicity, safety and reactogenicity of the RSVPreF3 
OA investigational vaccine when co-administered with HZ/su vaccine in adults ≥50 YOA, as 
compared to when the RSVPreF3 OA investigational vaccine and the HZ/su vaccine are 
administered separately. 
Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints 
Primary* 
To demonstrate non-inferiority of the humoral 
immune response to two doses of HZ/su 
vaccine when the first dose of HZ/su vaccine is 
co-administered with RSVPreF3 OA 
investigational vaccine, compared to two doses 
of HZ/su vaccine administered alone. 
• 
Anti-gE antibody concentrations expressed as 
group GMC ratio between the Control group and 
the Co-ad group, 1-month after the second dose of 
HZ/su vaccine. 
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Objectives 
Endpoints 
To demonstrate the non-inferiority of 
RSVPreF3 OA investigational vaccine when 
co-administered with the first dose of HZ/su 
vaccine, compared to RSVPreF3 OA 
investigational vaccine administered alone. 
• 
RSV-A neutralizing titers expressed as group 
GMT ratio between the Control group and the 
Co-ad group, 1-month after the RSVPreF3 OA 
investigational vaccine dose. 
• 
RSV-B neutralizing titers expressed as group 
GMT ratio between the Control group and the 
Co-ad group, 1-month after the RSVPreF3 OA 
investigational vaccine dose. 
Secondary 
To evaluate the anti-gE humoral immune 
response to two doses of HZ/su vaccine, when 
the first dose of HZ/su vaccine is 
co-administered with RSVPreF3 OA 
investigational vaccine or administered alone. 
• 
Anti-gE antibody concentrations expressed as 
seropositivity rate with exact 95% CI at pre 
vaccination and at 1-month post-second dose of 
HZ/su vaccine. 
• 
Anti-gE antibody concentrations expressed as 
GMC with 95% CI at pre-vaccination and at 
1-month post-second dose of HZ/su vaccine. 
• 
Anti-gE antibody concentrations expressed as MGI 
with 95% CI from pre-vaccination to 1-month 
post-second dose of HZ/su vaccine. 
• 
Vaccine response rate with exact 95% CIs at 
1-month post-second dose of HZ/su vaccine. 
To evaluate the humoral immune response to 
RSVPreF3 OA investigational vaccine when 
co-administered with the first dose of HZ/su 
vaccine or administered alone. 
• 
RSV-A neutralizing titers expressed as GMT at 
pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
• 
RSV-A neutralizing titers expressed as MGI at 
1-month after the RSVPreF3 OA investigational 
vaccine dose. 
• 
RSV-B neutralizing titers expressed as GMT at 
pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
• 
RSV-B neutralizing titers expressed as MGI at 
1-month after the RSVPreF3 OA investigational 
vaccine dose. 
To evaluate the safety and reactogenicity 
following administration of the RSVPreF3 OA 
investigational vaccine and the HZ/su vaccine, 
co-administered or administered alone. 
• 
Percentage of participants reporting each solicited 
administration site and systemic event with onset 
within 7 days after vaccine administration (i.e., the 
day of vaccination and 6 subsequent days). 
• 
Percentage of participants reporting unsolicited 
AEs with onset within 30 days after vaccine 
administration (i.e., the day of vaccination and 
29 subsequent days). 
• 
Percentage of participants reporting all SAEs after 
vaccine administration (Day 1) up to study end 
(6 months after last vaccination). 
• 
Percentage of participants reporting all pIMDs 
after vaccine administration (Day 1) up to study 
end (6 months after last vaccination). 
 
 
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Abbreviations: AE=adverse event; CI=confidence interval; gE=glycoprotein E; GMC=geometric mean 
concentration; GMT=geometric mean titer; HZ/su=herpes zoster recombinant subunit; MGI=mean geometric 
increase; OA=older adult; pIMD=potential immune-mediated disease; RSV=respiratory syncytial virus; 
SAE=serious adverse event. 
* Zoster and RSV-A related endpoints will be assessed as co-primary. RSV-B related endpoints will be assessed 
as sequential to the success of Zoster and RSV-A. 
 
Overall Design: 
Experimental design: Phase III, open-label, randomized, controlled, multi-country study with 
2 parallel groups.  
Study groups and Randomization: Approximately 530 eligible participants will be 
randomly (1:1) assigned to 2 study groups (approximately 265 participants each) using a 
centralized randomization system on internet at Visit 1 (Day 1). The randomization algorithm 
will use a minimization procedure accounting for age (50 to 59, 60 to 69, or ≥70 years) and 
center. Minimization factors will have equal weight in the minimization algorithm. 
Overall, participants will be enrolled in three age categories with a balance between males and 
females. It is intended to enroll: 
Approximately 30% of participants 50 to 59 YOA, approximately 30% of participants 60 to 
69 YOA, approximately 25% of participants ≥70 YOA. The remaining 15% can be distributed 
freely across the three age categories. The enrollment of participants as per the age categories, 
and percentage of participants in each age category, if any, will be guided by the feasibility 
assessment. 
Approximately 40% of participants from each sex; the remaining 20% can be distributed 
freely between the two sexes. 
Duration of study: The total duration of the study, per participant, will be approximately 
8 months.  
• Co-administration (Co-ad) group: Study interventions will be administered on Visit 1 
(Day 1) in which participants will receive both HZ/su vaccine and RSV PreF3 OA 
investigational vaccine; and on Visit 3 (Day 61) in which the second dose of HZ/su 
vaccine will be administered. A total of four site visits (Visit 1 [Day 1], Visit 2 [Day 31], 
Visit 3 [Day 61] and Visit 4 [Day 91]) and a remote contact 6 months post-last vaccination 
are needed.  
• Control group: Study interventions will be administered on Visit 1 (Day 1) in which 
participants will receive HZ/su vaccine; Visit 2 (Day 31) in which participants will receive 
RSV PreF3 OA investigational vaccine; and Visit 3 (Day 61) in which participants will 
receive the second dose of HZ/su vaccine. A total of four site visits (Visit 1 [Day 1], Visit 
2 [Day 31], Visit 3 [Day 61] and Visit 4 [Day 91]) and a remote contact 6 months post-last 
vaccination are needed. 
Safety monitoring: The study will be conducted with oversight by the project Safety Review 
Team. 
 
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1.2 
Schema 
Figure 1 
Study Schema 
 
Abbreviations: AE=Adverse Event; Co-ad group=Co-administration group; D=Day; Hz/su=herpes zoster 
recombinant subunit; GSK=GlaxoSmithKline; N=Number of participants; pIMD=potential Immune-Mediated 
Disease; RSV=RSVPreF3 OA investigational vaccine; SAE=Serious Adverse Event; SRT=Safety Review 
Team. 
 
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11At Visits 1 and 3 (Co-ad group), pregnancy information must be recorded prior to study intervention administration. Pregnancies will be followed as described 
in Section 10.4.3. 
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11SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to study vaccine 
administration) up to study end. 
12At Visits 1, 2, and 3 (Control group), pregnancy information must be recorded prior to study intervention administration. Pregnancies will be followed as 
described in Section 10.4.3. 
 
Table 3 
Interval Between Study Visits (Co-ad Group) 
Interval 
Planned visit interval 
Allowed interval range* 
Visit 1 (Day 1)→Remote Contact (Day 8)** 
8 days 
- 
Visit 1 (Day 1)→Visit 2 (Day 31) 
30 days 
30-42 days 
Visit 1 (Day 1)→Visit 3 (Day 61) 
60 days 
60-84 days 
Visit 3 (Day 61)→Visit 4 (Day 91) 
30 days 
30-42 days 
Visit 3 (Day 61)→Phone contact 
180 days 
180-210 days 
*Participants may not be eligible for the HZ/su and RSV Per Protocol Set (PPS) if the visits happen beyond this interval. Intervals between visits and phone 
contact do not affect HZ/su and RSV PPS eligibility. 
**Day 8 Remote Contact is applicable to the sentinel group only. 
 
Table 4 
Interval Between Study Visits (Control Group) 
Interval 
Planned visit interval 
Allowed interval range* 
Visit 1 (Day 1)→Remote Contact (Day 8)** 
8 days 
- 
Visit 1 (Day 1)→Visit 2 (Day 31) 
30 days 
30-42 days 
Visit 2 (Day 31)→Visit 3 (Day 61) 
30 days 
30-42 days 
Visit 3 (Day 61)→Visit 4 (Day 91) 
30 days 
30-42 days 
Visit 3 (Day 61)→Phone contact 
180 days 
180-210 days 
*Participants may not be eligible for the HZ/su and RSV Per Protocol Set (PPS) if the visits happen beyond this interval. Intervals between visits and phone 
contact do not affect HZ/su and RSV PPS eligibility. 
**Day 8 Remote Contact is applicable to the sentinel group only.
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2.0 INTRODUCTION 
2.1 
Study Rationale 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial 
virus (RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) 
adjuvanted with liposome-based AS01E system, against RSV-associated (subtypes A and B) 
disease. In a large phase III vaccine clinical trial in adults aged 60 years and above, the 
vaccine candidate demonstrated overall vaccine efficacy of 82.6% (96.95% Confidence 
Interval [CI], 57.9 – 94.1) against RSV lower respiratory tract disease (RSV-LRTD).1 The 
vaccine was well tolerated with a favorable safety profile. The study is still ongoing to assess 
other endpoints.  
The present study will assess the immunogenicity, safety and reactogenicity of the 
RSVPreF3 OA investigational vaccine when co-administered with Herpes Zoster recombinant 
subunit (HZ/su) vaccine in adults ≥50 YOA, as compared to when the RSVPreF3 OA 
investigational vaccine and the HZ/su vaccine are administered alone. 
2.2 
Background 
Respiratory syncytial virus can cause severe lower respiratory tract infection in older adults 
and adults with chronic medical conditions including cardiopulmonary and 
immunocompromising conditions.  
Based on epidemiological data collected prospectively in 2008-2010 in 14 countries 
worldwide (including North America, Europe, and East Asia), the average percentage of 
documented RSV infection in older adults with influenza-like illness is 7.4%, with values 
between 0% and 17.1% across countries.2 In 2015, an estimated 1.5 million episodes of RSV 
related acute respiratory illness occurred in older adults in industrialized countries; 
approximately 14.5% of these episodes involved a hospital admission.3 Further information on 
RSV incidence and disease burden can be found in the Investigator’s Brochure (IB). 
GSK’s herpes zoster (HZ) vaccine is a non-live, recombinant subunit (su) vaccine (Shingrix, 
hereby referred to as HZ/su vaccine) and consists of the varicella zoster virus (VZV) 
glycoprotein E (gE) as an active ingredient, together with the liposome-based adjuvant system 
AS01B. Earlier studies have established that HZ/su vaccine is highly efficacious, and induces 
strong cellular and humoral immune responses with a clinically acceptable safety profile in 
adults ≥50 YOA.4,5,6  
The HZ/su vaccine is indicated for use in healthy adults ≥50 YOA in United States (US), 
Canada, and United Kingdom (UK).7,8,9 Since both vaccines will be indicated for use in 
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individuals of overlapping age groups, evaluation of the co-administration of the RSVPreF3 
OA and HZ/su vaccines is of interest.  
2.3 
Benefit/Risk Assessment 
2.3.1 
Risk Assessment 
Detailed information about the known and expected benefits and potential risks and 
reasonably expected adverse events (AEs) of the RSVPreF3 OA investigational vaccine can 
be found in the Investigator’s Brochure (IB).  
Study participants must be observed closely for at least 30 minutes after the administration of 
the study interventions. The duration of the observation period can be extended at the 
investigator’s discretion. Appropriate medical treatment must be readily available during the 
observation period in case of anaphylaxis and/or syncope.  
Table 5 
Potential/Identified Risk and Mitigation Strategy 
Important Potential/Identified Risk 
Mitigation Strategy 
RSV Investigational Vaccine 
Potential immune-mediated diseases are considered a 
potential risk, as for all vaccines containing an 
adjuvant system. 
Refer to Section 10.3.3 for details 
Syncope and hypersensitivity reactions (including 
anaphylaxis). 
 
Participants with a history of hypersensitivity or 
severe allergic reaction to any component of the 
vaccine are excluded from study enrollment. 
All participants will remain under observation at the 
clinical center for at least 30 minutes after 
vaccination. 
Appropriate medical care must be readily available 
during this period 
HZ/su Vaccine 
Guillain-Barré Syndrome  
Close monitoring of GBS will be conducted per study 
protocol and analysis of safety data generated through 
clinical trials and other sources as part of pIMDs 
(including GBS). 
The potential risk of events of possible autoimmune 
etiology to occur is mentioned in the ICF. In addition, 
the ICF advises participants to contact the study 
doctor or study staff immediately, should any 
symptoms be considered of concern.  
All pIMDs (including GBS) will be collected up to 
end of study.  
Potential immune-mediated diseases are considered a 
potential risk, as for all vaccines containing an 
adjuvant system. 
Refer to Section 10.3.3 for details. 
Syncope and hypersensitivity reactions (including 
Participants with a history of hypersensitivity or 
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anaphylaxis). 
severe allergic reaction to any component of the 
vaccine are excluded from study enrollment. 
 
All participants will remain under observation at the 
clinical center for at least 30 minutes after 
vaccination. 
Appropriate medical care must be readily available 
during this period 
Study Procedures 
Intramuscular vaccination commonly precipitates a 
transient and self-limiting administration site 
inflammatory reaction. This may typically include 
pain at injection site, erythema/redness, and swelling. 
As a mitigation strategy, physicians can implement 
the measures that they consider necessary. 
Pain and bruising may occur at the site where blood 
is drawn. 
As a mitigation strategy, physicians can implement 
the measures that they consider necessary. 
Syncope (fainting) can occur following or even 
before any blood draw as a psychogenic response to 
the needle insertion. 
Blood samples will be obtained in seated or supine 
position by a trained professional and medical 
assistance will be available. 
Participants who mention experiencing previous 
episodes of fainting or dizziness before, during or 
after a blood draw, will remain under observation at 
the clinical center until deemed necessary by site 
personnel.  
Appropriate medical care must be readily available 
during this period. 
Abbreviations: GBS=Guillain-Barré Syndrome; ICF=informed consent form; pIMD=potential immune-mediated 
disease; RSV=respiratory syncytial virus. 
 
In this study women of childbearing potential of 50-59 years of age can be included.  
On 25 February 2022, GSK decided to stop enrollment and vaccination in RSV maternal 
vaccine studies involving pregnant women. This decision was taken because of an observed 
imbalance in the proportions of both preterm births (PTB) and neonatal deaths (death of an 
infant within the first 28 days of life) in the treatment group vs. the placebo group in the 
RSV-MAT-009 study. Subsequently, the enrollment and vaccination in all studies of the RSV 
maternal vaccine candidate involving women of childbearing potential have also been 
stopped.  
Following Day 43 post-birth interim analysis (DLP 04 October 2022) of RSV MAT-009 
study, GSK agreed that preterm birth is an identified risk for the pregnant women population, 
for the RSV maternal vaccine candidate. The observed numerical imbalance in neonatal 
deaths is not an independent safety signal but a consequence of the imbalance in preterm birth. 
GSK has discontinued the further development on this RSV maternal candidate vaccine. 
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The safety concern is specific to women who received the RSV maternal vaccine candidate 
during the late second or third trimester of pregnancy. To date, analyses of the available safety 
data have not established what caused the imbalances that were observed. Further analysis of 
the data to better understand the safety concerns is ongoing.  
The vaccine candidate for older adults (OA) contains the same RSV antigen as the RSV 
maternal candidate vaccine but RSV OA vaccine is combined with GSK’s established AS01E 
adjuvant to boost the immune response in the older adult population.  
The Older Adult RSV vaccine trials in participants 60 years of age and older are closely 
monitored for safety with all available safety data reviewed internally. In addition, the 
phase III RSV OA=ADJ-006 clinical study is monitored by an IDMC on an ongoing basis. 
The IDMC met most recently on 1 December 2022 and did not raise any concerns in the older 
adult population. The RSV OA vaccine has not been studied in pregnant women to date. 
In the current study the inclusion of all participants will be restricted to those 50 years of age 
and above. This age cut-off has been chosen since there is a recommendation for use of 
Shingrix as of 50 YOA. For women, the incidence of spontaneous pregnancies is 4 in 100,000 
in this age group.10 As a precautionary measure, all women of childbearing potential will be 
required to use adequate contraception and have a negative pregnancy test prior to 
vaccination. 
2.3.2 
Benefit Assessment 
The participants may have the benefit of being protected against RSV infection during the 
active season. In a large Phase III vaccine clinical trial in adults aged 60 years and older, the 
RSVPreF3 investigational vaccine candidate demonstrated overall vaccine efficacy of 82.6% 
(96.95% confidence interval [CI], 57.9 to 94.1) against RSV lower respiratory tract disease 
(RSV-LRTD). The vaccine was well tolerated with a favorable safety profile.  
All participants in this study will also receive herpes zoster recombinant subunit (HZ/su) 
vaccine as part of this study which is indicated for the prevention of herpes zoster among 
healthy adults ≥50 YOA.  
An indirect benefit is that the information obtained in this study will generate more knowledge 
about the RSV vaccine and the possibility to be co-administered with HZ/su vaccine. Another 
benefit for all study participants may include gaining information about their general health 
status through the recurrent medical evaluations/assessments associated with this study (i.e., 
physical examination). 
2.3.3 
Overall Benefit Risk Conclusion 
Considering the measures taken to minimize risk to participants participating in this study, the 
potential or recognized risks identified in association with the study vaccines and study 
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2.3.3 
Overall Benefit Risk Conclusion 
Considering the measures taken to minimize risk to participants participating in this study, the 
potential or recognized risks identified in association with the study vaccines and study 
procedures are justified by the potential benefits that may be afforded to the participants 
receiving these vaccines and by the value of the information to be gained. 
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3.0 OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
 
Table 6 
Objectives, Endpoints, and Estimands 
Objectives 
Endpoints 
Primary* 
To demonstrate non-inferiority of the humoral 
immune response to two doses of HZ/su vaccine 
when the first dose of HZ/su vaccine is 
co-administered with RSVPreF3 OA investigational 
vaccine, compared to two doses of HZ/su vaccine 
administered alone. 
• 
Anti-gE antibody concentrations expressed 
as group GMC ratio between the Control 
group and the Co-ad group, 1-month after the 
second dose of HZ/su vaccine. 
To demonstrate the non-inferiority of RSVPreF3 OA 
investigational vaccine when co-administered with 
the first dose of HZ/su vaccine, compared to 
RSVPreF3 OA investigational vaccine administered 
alone. 
• 
RSV-A neutralizing titers expressed as group 
GMT ratio between the Control group and 
the Co-ad group, 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
• 
RSV-B neutralizing titers expressed as group 
GMT ratio between the Control group and 
the Co-ad group, 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
Secondary 
To evaluate the anti-gE humoral immune response to 
two doses of HZ/su vaccine, when the first dose of 
HZ/su vaccine is co-administered with RSVPreF3 
OA investigational vaccine or administered alone. 
• 
Anti-gE antibody concentrations expressed 
as seropositivity rate with exact 95% CI at 
pre vaccination and at 1-month post-second 
dose of HZ/su vaccine. 
• 
Anti-gE antibody concentrations expressed 
as GMC with 95% CI at pre-vaccination and 
at 1-month post-second dose of HZ/su 
vaccine. 
• 
Anti-gE antibody concentrations expressed 
as MGI with 95% CI from pre-vaccination to 
1-month post-second dose of HZ/su vaccine. 
• 
Vaccine response rate with exact 95% CIs at 
1-month post-second dose of HZ/su vaccine. 
To evaluate the humoral immune response to 
RSVPreF3 OA investigational vaccine when 
co-administered with the first dose of HZ/su vaccine 
or administered alone. 
• 
RSV-A neutralizing titers expressed as GMT 
at pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
• 
RSV-A neutralizing titers expressed as MGI 
at 1-month after the RSVPreF3 OA 
investigational vaccine dose. 
• 
RSV-B neutralizing titers expressed as GMT 
at pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose. 
• 
RSV-B neutralizing titers expressed as MGI 
at 1-month after the RSVPreF3 OA 
investigational vaccine dose. 
To evaluate the safety and reactogenicity following 
administration of the RSVPreF3 OA investigational 
• 
Percentage of participants reporting each 
solicited administration site and systemic 
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Objectives 
Endpoints 
vaccine and the HZ/su vaccine, co-administered or 
administered alone. 
event with onset within 7 days after vaccine 
administration (i.e., the day of vaccination 
and 6 subsequent days). 
• 
Percentage of participants reporting 
unsolicited AEs with onset within 30 days 
after vaccine administration (i.e., the day of 
vaccination and 29 subsequent days). 
• 
Percentage of participants reporting all SAEs 
after vaccine administration (Day 1) up to 
study end (6 months after last vaccination). 
• 
Percentage of participants reporting all 
pIMDs after vaccine administration (Day 1) 
up to study end (6 months after last 
vaccination). 
Abbreviations: AE=adverse event; CI=confidence interval; gE=glycoprotein E; GMC=geometric mean 
concentration; GMT=geometric mean titer; HZ/su=herpes zoster recombinant subunit; MGI=mean geometric 
increase; OA=older adult; pIMD=potential immune-mediated disease; RSV=respiratory syncytial virus; 
SAE=serious adverse event. 
* Zoster and RSV-A related endpoints will be assessed as co-primary. RSV-B related endpoints will be assessed 
as sequential to the success of Zoster and RSV-A. 
 
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4.0 STUDY DESIGN 
4.1 
Overall Design 
The study design diagram is provided in Figure 1. 
Experimental design: Phase III, open-label, randomized, controlled, multi-country study with 
2 parallel groups.  
Study groups and Randomization: Approximately 530 eligible participants will be 
randomly (1:1) assigned to 2 study groups (approximately 265 participants each) using a 
centralized randomization system on internet at Visit 1 (Day 1). The randomization algorithm 
will use a minimization procedure accounting for age (50 to 59. 60 to 69, or 70 years) and 
center. Minimization factors will have equal weight in the minimization algorithm. 
• Enrollment rules are described in Section 4.1.2. 
Duration of study: The total duration of the study, per participant, will be approximately 
8 months.  
• Co-administration (Co-ad) group: Study interventions will be administered on Visit 1 
(Day 1) in which participants will receive both HZ/su vaccine and RSVPreF3 OA 
investigational vaccine; and on Visit 3 (Day 61) in which the second dose of HZ/su 
vaccine will be administered. A total of four site visits (Visit 1 [Day 1], Visit 2 [Day 31], 
Visit 3 [Day 61] and Visit 4 [Day 91]) and a remote contact 6 months post-last vaccination 
are needed.  
• Control group: Study interventions will be administered on Visit 1 (Day 1) in which 
participants will receive HZ/su vaccine; Visit 2 (Day 31) in which participants will receive 
RSVPreF3 OA investigational vaccine; and Visit 3 (Day 61) in which participants will 
receive the second dose of HZ/su vaccine. A total of four site visits (Visit 1 [Day 1], Visit 
2 [Day 31], Visit 3 [Day 61] and Visit 4 [Day 91]) and a remote contact 6 months post-last 
vaccination are needed. 
The description of the vaccine(s)/product is presented in Table 8. 
4.1.1 
Overview of Recruitment Plan  
No separate screening visit is planned for this study. The study is planned to be conducted at 
sites in multiple countries. The recruitment plan will be defined by each participating site. 
The recruitment plan may be adapted based on the actual number of participants enrolled in 
each country. In case a site would fall behind in participant recruitment, a redistribution of the 
enrollment target per site in the participating countries may be made. This would allow the 
other participating sites to enroll additional participants to ensure full and timely enrollment of 
the overall targeted number of participants specified in this protocol. 
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Randomization will be put on pause while the Safety Review Team (SRT, Section 10.1.6) 
reviews the 7-day safety data for the sentinel group (10% of total sample size, 27 participants 
in the co-administration group and 27 participants in the control group) and will resume if the 
recommendation of the SRT is to continue with randomization. 
The procedures for participants identification/recruitment must be approved by the 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) together with the 
material intended for participants identification/recruitment and participants use. 
4.1.2 
Enrollment Rules 
Overall, participants will be enrolled in three age categories reflecting an approximate age 
distribution and disease burden in the general population with a balance between males and 
females. It is therefore intended to enroll: 
• Approximately 30% participants 50 to 59 YOA, approximately 30% of participants 60 to 
69 YOA, and approximately 25% of participants ≥70 YOA. The remaining 15% can be 
distributed freely across the three age categories. The enrollment of participants as per the 
age categories, and percentage of participants in each age category, if any, will be guided 
by the feasibility assessment. 
• Approximately 40% of participants from each sex; the remaining 20% can be distributed 
freely between the two sexes. 
4.2 
Scientific Rationale for Study Design 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial virus 
(RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) against 
RSV-associated (subtypes A and B) disease. The vaccine development is currently in Phase 
III, and immunogenicity, safety, and reactogenicity of the candidate vaccine when 
co-administered with other vaccines are being investigated. 
Shingrix is a vaccine indicated for active immunization for the prevention of shingles and its 
complications among healthy from 50 years and above.  
Both RSVPreF3 OA investigational vaccine and HZ/su vaccine will be available for 
individuals with overlapping age groups. The current study is designed to provide 
reactogenicity, safety, and immunogenicity data when RSV PreF3 OA vaccine is 
co-administered with HZ/su vaccine or when administered with a gap of 4 weeks. These data 
are expected to help public health authorities provide more evidence-based guidance and 
health care providers to make decisions on such vaccine co-administrations. 
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4.3 
Justification for Dose of RSVPreF3 OA Investigational Vaccine 
Based on the results up to 1-month post-dose 2 from study RSV OA=ADJ-002, a single dose 
regimen (0.5 mL) and the 120 µg RSVPreF3/AS01E formulation were selected for further 
evaluation in the Phase 3 clinical program.6 The RSV OA=ADJ-002 study was designed to 
assess the immunogenicity of a 2-dose AS01-adjuvanted or unadjuvanted vaccine 
administered according to a 0-, 2-month schedule with the aim to maximize the immune 
response against RSV and vaccine efficacy over several seasons. Based on the data from 
clinical development programs for AS01-adjuvanted protein antigen vaccines in OA, such as 
Shingrix and the chronic obstructive pulmonary disease (COPD) investigational vaccine, it 
was expected that immunological responses would reach higher levels 1-month post dose 2 as 
compared with 1-month post dose 1. However, the RSV OA=ADJ-002 results demonstrated 
that the second dose given 2 months after the first dose had no added value in terms of 
humoral and/or cellular immune responses. The humoral response, both in terms of RSV-A 
neutralizing geometric mean titers (GMTs) and RSVPreF3 IgG geometric mean 
concentrations (GMCs), peaked 1-month after the first dose, and the second dose did not 
increase the level observed after first dose. 
The results from study RSV OA=ADJ-002 demonstrated statistically significant superiority of 
the 120 µg formulations in terms of RSV-A neutralizing titers over at least one of the 30 µg 
and 60 µg formulations with the same adjuvant content or unadjuvanted. The data 
demonstrated an immunologic benefit of any AS01E or AS01B formulations over 
unadjuvanted formulations in terms of frequency of RSVPreF3-specific CD4+ T cells 
expressing at least 2 markers. Importantly, despite lower baseline observed in OA, the AS01 
containing formulations induced CD4+ T cells frequencies at a close or similar level as in 
young adults, that is not observed with the unadjuvanted formulations. 
There was no safety concern detected in unadjuvanted groups to be linked to the RSVPreF3 
antigen assessed for the first time in OA. The acceptable safety/reactogenicity profile in all 
120 µg groups, together with the immunological benefit demonstrated for the 120 µg antigen 
dose, supports the selection of a 120 µg based formulation. The results also showed that all the 
AS01-adjuvanted formulations evaluated are considered to have a clinically acceptable safety 
profile. The AS01-adjuvanted formulation with the lowest reactogenicity profile, i.e., the 
AS01E-based formulation, was selected. The immunological response observed after 
1 vaccine dose of the AS01E-based formulation is considered adequate for a RSVPreF3 OA 
candidate vaccine. 
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she returns for the last visit as 
described in the protocol. 
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End of Study is the last subject last visit (LSLV) (contact at 6 months post-last dose). 
4.5 
Study Holding Rules 
Vaccine administration in this study will be staggered: first, a sentinel group of participants 
(10% of total sample size, 27 participants in the co-administration group and 27 participants in 
control group) will be vaccinated and followed-up for 7 days after Visit 1. Randomization will 
be paused after participants in the sentinel group have received Visit 1 vaccinations. All 
cumulative safety data from the 7 days following Visit 1 vaccinations from the sentinel group 
participants of both study groups will be reviewed at the predefined scheduled SRT (Figure 1 
and Section 10.1.6) as per study protocol.  
The holding rules will be applicable for the cumulative safety data from the 27 participants of 
co-administration group. The holding rules are defined in the Table 7. If SRT judges that no 
safety concerns have been identified based on cumulative safety data assessment, then 
randomization pause can be lifted and remaining 90% of participants can be randomized and 
vaccinated. 
If the Investigator, site staff, any study team member from IQVIA, or GSK identify that any of 
the holding rule criteria or other safety concerns are met at any time during the recruitment of 
the sentinel group, randomization shall be temporarily put on pause and an ad hoc SRT review 
will be performed to review all cumulative safety data. Randomization shall also be 
temporarily put on pause and an ad hoc SRT review be performed if any safety concern is 
seen at any time during the study. Randomization can only be resumed following SRT 
recommendation. Any potential safety concern related to conduct of the study will be 
managed as per internal GSK process. The decision on whether to continue with 
randomization as planned or otherwise (including but not limited to, modification of the study 
conduct/study protocol or stopping the study) will be communicated to the study sites. The 
investigator is not permitted to restart randomization until the receipt of favorable written 
documentation of safety evaluation. 
No formal assessment of holding rules will be observed after the predefined scheduled SRT 
review.  
Table 7 
Study Holding Rules  
Holding rule 
Event 
Number or percentage 
of participants 
1a 
Death or any life-threatening SAE that cannot be 
reasonably attributed to a cause other than 
vaccination as per Investigator or Sponsor 
assessment 
1/27 participants 
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1b 
Any non-life-threatening SAE that cannot be 
reasonably attributed to a cause other than 
vaccination as per Investigator or Sponsor 
assessment 
3/27 participants 
1c 
Any withdrawal from the study (by investigator or 
subject request) following a Grade 3 AE that 
cannot be reasonably attributed to a cause other 
than vaccination as per Investigator or Sponsor 
assessment 
3/27 participants 
1d 
Any solicited systemic AE leading to 
hospitalization within the 7-day (Days 1-7) 
post-vaccination period 
2/27 participants 
2a 
Any Grade 3 solicited systemic AE (lasting 
48 hours or more) within the 7-day (Day 1-7) 
post-vaccination period 
6/27 participants 
2b 
Any Grade 3 unsolicited AE, that can be 
reasonably attributed to the vaccination as per 
Investigator or Sponsor assessment, within the 
7-day (Day 1-7) post-vaccination period 
3/27 participants 
Abbreviations: AE=adverse events; SAE=serious adverse events.  
 
Risk assessment for study holding rules 
Figure 1 illustrates that, with 27 participants in the co-administration group in the 
pre-specified scheduled SRT review: 
• Holding rule 1a has more than 76% chance of not being met for vaccination with a true 
incidence rate of 1% and has more than 94% chance of being met for vaccination with a 
true incidence rate above 10%. 
• Holding rule 1d has more than 61% chance of not being met for vaccination with a true 
incidence rate of 5% and has more than 93% chance of being met for vaccination with a 
true incidence rate above 15%. 
• Each holding rule 1b, 1c and 2b has more than 48% chance of not being met for 
vaccination with a true incidence rate below 10% and more than 79% chance of being met 
for vaccination with a true incidence rate above 15%. 
• Holding rule 2a has more than 79% chance of not being met for vaccination with a true 
incidence rate below 15% and more than 70% chance of being met for vaccination with a 
true incidence rate above 25%.  
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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: 
All participants must satisfy ALL the following criteria at study entry: 
• A male or female participant 50 YOA at the time of the first study intervention 
administration. 
• Female participants of non-childbearing potential may be enrolled in the study. Non 
childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral 
salpingectomy or post-menopause. Refer to Section 10.4.1 for definitions of women not 
considered as women of childbearing potential, and menopause. 
• Female participants of childbearing potential may be enrolled in the study, if the 
participant: 
o has practiced adequate contraception from 1 month prior to study intervention 
administration. 
o has a negative pregnancy test on the day of and prior to study intervention 
administration. 
o has agreed to continue effective contraception until the end of the study. 
o Refer to Section 10.4 for definitions of woman of childbearing potential and adequate 
contraception. 
• Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g., completion of the electronic diary [eDiary], return for 
follow-up visits, ability to access and utilize a phone or other electronic communications). 
Note: In case of physical incapacity that would preclude the self-completion of the eDiary, 
either site staff can assist the participant (for activities performed during site visits) or the 
participant may assign a caregiver* to assist him/her with this activity (for activities 
performed at home). However, at no time will the site staff or caregiver* evaluate the 
participant’s health status while answering eDiaries or make decisions on behalf of the 
participant. 
*A ‘caregiver’ is a person who has a continuous caring role for a participant or may be a person having 
substantial periods of contact with a participant and/or is engaged in his/her daily health care (e.g., a 
relative of the participant including family members or friends). 
• Written or witnessed informed consent obtained from the participant prior to any study 
specific procedure being performed. 
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• Participants living in the general community or in an assisted-living facility that provides 
minimal assistance, such that the participant is primarily responsible for self-care and 
activities of daily living. 
• Participants who are medically stable in the opinion of the investigator at the time of first 
study intervention administration. Participants with chronic stable medical conditions with 
or without specific treatment, such as diabetes mellitus, hypertension, or cardiac disease, 
are allowed to participate in this study if considered by the investigator as medically 
stable. 
 
5.2 
Exclusion Criteria  
The following criteria should be checked at the time of study entry. The potential participant 
MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1 
Medical conditions 
• Pregnant or lactating female. 
• Female planning to become pregnant or planning to discontinue contraceptive precautions. 
• Any confirmed or suspected autoimmune disorders, immunosuppressive or 
immunodeficient condition resulting from disease (e.g., current malignancy, human 
immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used 
during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), 
based on medical history and physical examination (no laboratory testing required). 
• History of any reaction or hypersensitivity (e.g., anaphylaxis) likely to be exacerbated by 
any component of the study interventions, in particular any history of severe allergic 
reaction to any vaccine component. 
• History of Guillain-Barré syndrome. 
• Any history of dementia or any medical condition that moderately or severely impairs 
cognition. 
Note: If deemed necessary for clinical evaluation, the investigator can use tools such as 
Mini-Mental State Examination (MMSE), Mini-Cog or Montreal Cognitive Assessment 
(MoCA) to determine cognition levels of the participant. 
• Recurrent or uncontrolled neurological disorders or seizures. Participants with 
medically-controlled chronic neurological diseases can be enrolled in the study as per 
investigator assessment, provided that their condition will allow them to comply with the 
requirements of the protocol (e.g., completion of the eDiary, attend regular phone 
calls/study site visits). 
• Significant underlying illness that in the opinion of the investigator would be expected to 
prevent completion of the study (e.g., life-threatening disease likely to limit survival up to 
study end). 
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• Any medical condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• Clinically suspected or polymerase chain reaction (PCR)-confirmed ongoing episode of 
herpes zoster. 
5.2.2 
Prior and Concomitant Therapy 
• History of previous vaccination with any licensed or investigational recombinant 
adjuvanted zoster vaccine (HZ/su vaccine; Shingrix) before the study start or planned 
receipt through study participation. 
• History of previous vaccination with any licensed or investigational live herpes zoster 
vaccine (Zostavax) in the last 2 years from enrollment11, or planned receipt through study 
participation. 
• Previous vaccination with licensed or investigational RSV vaccine. 
• 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 first dose 
of study interventions, or their planned use during the study period. 
• Planned or actual administration of a vaccine not foreseen by the study protocol in the 
period starting 30 days before the first study intervention administration and ending 
30 days after the last study intervention administration.  
o In the case of COVID-19 and inactivated/subunit/split influenza vaccines, this time 
window can be decreased to 14 days before and after each study intervention 
administration provided COVID-19 vaccine use is in line with local governmental 
recommendations. 
Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g., 
a pandemic) is recommended and/or organized by the 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 governmental 
recommendations and that the Sponsor is notified accordingly.  
• Planned or actual administration of adjuvanted quadrivalent influenza vaccine influenza 
vaccine not foreseen by the study protocol in the period starting 30 days before the first 
study intervention administration and ending 30 days after the last study intervention 
administration. 
• Administration of long-acting immune-modifying drugs during the period starting 
180 days before the administration of first dose of study interventions or planned 
administration at any time during the study period (e.g., infliximab). 
• Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 90 days before the administration of first dose of study 
interventions or planned administration during the study period. 
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• Chronic administration (defined as more than 14 consecutive days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 90 days 
prior to the first study intervention dose or planned administration during the study period. 
For corticosteroids, this will mean prednisone 20 mg/day, or equivalent. Inhaled, topical 
or intra-articular steroids are allowed. 
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 vaccine/product (IMP) (drug or invasive medical device). 
Note: European Economic Community (EEC) directive 93/42/EEC defines an invasive 
medical device as ‘A device which, in whole or in part, penetrates inside the body, either 
through a body orifice or through the surface of the body’. 
5.2.4 
Other exclusions 
• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator 
to render the potential participant unable/unlikely to provide accurate safety reports or 
comply with study procedures. 
• Bedridden participants. 
• Planned move during the study conduct that prohibits participation until study end. 
• Participation of any study personnel or their immediate dependents, family, or household 
members. 
 
5.3 
Lifestyle Considerations 
Meals and Dietary Restrictions 
No meal or dietary restrictions are required for study participation. No lifestyle restrictions are 
applicable for this study. 
5.4 
Caregiver Support 
Study participants may decide to assign a caregiver to help them fulfill the study procedures. 
Please refer to the Glossary of Terms for the definition of a caregiver. 
A caregiver can be appointed by the participant at any time during the study, when the 
participant feels it is necessary. Each caregiver should receive the caregiver information letter 
before providing support to the study participant. Ideally, a single caregiver should be 
appointed by the participant but, in some situations, it may happen that several caregivers will 
support a study participant throughout the conduct of the study. This should be recorded in the 
source documents. However, every effort should be done to ensure that only one caregiver 
enters the data into the eDiary to allow for timely completion. 
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Caregivers may help the study participants with performing some practical study procedures 
such as receiving or making phone calls to site staff, planning study visits, transcribing 
responses to diaries, transportation to and from the study site etc. However, at no time, the 
caregiver should evaluate the participant’s health status while answering diaries or make 
decisions on behalf of the participant. At the first study visit (Visit 1 [Day 1]) the site staff 
should inform the participant of the possibility to appoint a caregiver. Then at subsequent 
study visit(s), the site staff should check again with the participant if he/she wishes to appoint 
a caregiver or if there were or will be changes of caregiver. 
5.5 
Screen Failures 
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently randomized to study intervention/entered in the study. 
Limited data for screening failures (including reason for screening failure and any serious 
adverse events (SAEs) related to study participation, or to a concurrent GSK 
medication/vaccine from the time of consent obtained) will be collected and reported in the 
electronic case report form (eCRF). 
Individuals who do not meet the criteria for participation in this study (screen failure) but at 
some point, in the future are expected to meet the eligibility criteria may be rescreened. 
Individuals who are rescreened will be assigned a new participant number and will undergo 
the informed consent process, and then restart a new screening phase. 
5.6 
Criteria for Temporarily Delaying  
Study intervention administration may be postponed within the permitted time interval as 
deemed appropriate by the investigator until transient conditions cited below are resolved and 
prior to the EoS enrollment period:  
• Acute disease and/or fever at the time of study intervention administration. Refer to 
Section 1.3 (Schedule of Activities [SoA]) for definition of fever and location for 
measuring body temperature in this study.  
• Participants with a minor illness (such as mild diarrhea) without fever may be dosed at the 
discretion of the investigator.  
• 
Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-19) 
infection (e.g., fever, cough, etc.). The return of the participant to the site will follow the 
specific guidance from local public health and other competent authorities (e.g., free of 
symptoms, COVID-19 negative testing, etc.). 
• Participants with known contact with COVID-19 positive individual may be vaccinated at 
least 14 days after the exposure, provided that the participant remains symptom-free, and 
at the discretion of the investigator.  
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• In case of administration of inactivated, subunit or split influenza vaccines or COVID-19 
vaccines (fully licensed or with Emergency Use Authorization [EUA]): postponement of 
study intervention administration within given protocol timelines and prior to the end of 
the study enrollment period, to allow respect of at least 14 days interval between 
abovementioned influenza/COVID-19 vaccination and study intervention administration. 
• Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 
• Other issues (e.g., technical or administrative) preventing dose administration on day of 
visit. 
In case of delayed enrollment, all visit activities will be repeated when the participant is able 
to return for the visit.  
For Visit 1, if the planned study intervention administration is delayed, blood sampling does 
not need to be repeated if it was obtained during enrollment visit. The following procedures 
must be repeated prior to the delayed study intervention administration: 
• Urine pregnancy test 
• Body temperature 
• Re-check contraindications, warnings, and precautions to study intervention 
• Re-check inclusion/exclusion criteria 
Visit window for Visit 2 starts from day of first study intervention administration. 
For delay in the study intervention administration during Visit 2 (control group), and Visit 3 
(co-administration and control groups) the following procedures must be repeated: 
• Urine pregnancy test 
• Body temperature  
• Re-check contraindications, warnings, precautions to study intervention 
• Re-check inclusion/exclusion criteria 
 
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6.0 STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol. 
6.1 
Study Intervention(s) Administered 
Table 8 
Study Intervention(s) Administered 
Study Treatment 
Name: 
RSVPreF3 OA Investigational 
Vaccine 
Shingrix 
Vaccines/ product 
formulation 
RSVPreF3 
(120 µg) 
AS01E: QS-21* 
(25 µg), 
MPL (25 µg), 
liposomes; Water 
for injections  
VZV gE (50 µg) 
AS01B: QS-21* 
(50 µg), MPL 
(50 µg), liposomes; 
Water for injections 
Presentation 
Vial; powder for 
suspension for 
injection 
Vial; suspension for 
suspension for 
injection 
Vial; powder for 
suspension for 
injection 
Vial; suspension for 
suspension for 
injection 
Route of 
Administration 
Intramuscular use 
Intramuscular use 
Product category 
Biologic 
Biologic 
Type 
Study 
Study 
Administration site 
 
Location 
Deltoid 
Deltoid 
Laterality 
Co-ad group: Dominant 
Control group: Non-dominant 
Co-ad group: Non-dominant 
Control group: Non-dominant 
Number of doses to 
be administered 
1 
2 
Dose Volume** 
0.5 mL 
0.5 mL 
Packaging, 
labeling*** 
Refer to Pharmacy Manual for details 
Refer to Pharmacy Manual for details 
Manufacturer 
GSK 
GSK 
Abbreviations: AS01E/AS01B=adjuvant system 01; MPL=monophosphoryl lipid A; QS-21=Quillaja saponaria 
Molina, fraction 21; RSV=respiratory syncytial virus.  
*Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of Agenus Inc., a Delaware, USA 
corporation. 
**Refer to the Pharmacy Manual for the volume after reconstitution. 
*** Labeling is compliant with the requirements of applicable regulatory agencies. 
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6.1.1 
Medical Devices 
There are no GSK manufactured medical devices (or devices manufactured for GSK by a third 
party) provided for use in this study. Other medical devices (not manufactured by or for GSK) 
provided for use in this study are: thermometer, syringe, and needle. All medical devices are 
CE marked and will be used for their intended use. Instructions for medical device use are 
provided in the package insert. 
All device deficiencies (including malfunction, use error and inadequate labeling) shall be 
documented and reported by the investigator throughout the clinical investigation (see 
Sections 8.3.6 and 10.3) and appropriately managed by GSK.  
6.2 
Preparation, Handling, Storage, and Accountability 
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 may receive study intervention, and only authorized 
study site staff may 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 storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
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 site staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study interventions 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. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Participation Identification 
Participant identification numbers (IDs) will be assigned sequentially to the participants who 
have consented to participate in the study, according to the range of participant IDs allocated 
to each study center. The participant IDs will be documented in the eCRF. 
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The eligibility of the participant will be determined based on the inclusion and exclusion 
criteria listed in Section 5.0. The participant ID will be the participant’s unique identification 
number for all eCRFs and associated study documentation that will be used for duration of the 
study. If the participant is terminated from the study, their participant ID cannot be 
re-assigned. 
6.3.2 
Randomization to Study Intervention 
All eligible participants will be centrally randomized to the co-administration group and 
control group at a 1:1 ratio using Interactive Web Response System (IWRS) randomization 
(refer to Glossary of Terms for a definition of IWRS).  
The participants will receive a unique intervention number (refer to Glossary of Terms for a 
definition of a treatment number). Once a treatment number has been assigned, it cannot be 
re-assigned. 
6.3.3 
Intervention Allocation to the Participant 
Approximately 530 eligible participants will be randomly (1:1) assigned to 2 study groups 
using a centralized randomization system on internet at Visit 1 (Day 1). The randomization 
algorithm will use a minimization procedure accounting for age (50 to 59, 60 to 69, ≥70 years) 
and center. Minimization factors will have equal weight in the minimization algorithm. 
After obtaining the signed and dated Informed Consent Form (ICF) from the participant and if 
the participant is eligible, the delegated clinical trial staff will access IWRS. Upon entering the 
participant ID and age, the randomization system will determine the treatment group and 
provide the treatment number to be used for the trial intervention. The treatment number(s) to 
be used for subsequent dose administration(s) will be provided by the same IWRS. 
Instructions related to instances when IWRS is not available will be provide to the site. 
Refer to the IWRS user manual for additional information related to the treatment number 
allocation. 
6.3.4 
Allocation of Participants to Assay Subsets 
Immunogenicity assessments are planned as outlined in Section 8.1.  
Refer to Section 9.2 for descriptions of analysis populations. 
6.3.5 
Blinding and Unblinding 
This is an open-label study. The participant and principal investigator (PI) will not be blind to 
the intervention administered.  
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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 to be tested in 
the laboratory. There will be no link between the study intervention and the identity of the 
participant. 
6.4 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The mode of administration (i.e., 
intramuscularly), laterality, as well as the date and time of each dose administered in the clinic 
will be recorded in the source documents. See Section 6.1 for details in intervention 
administration. 
6.5 
Dose Modification 
Dose modifications are not planned or allowed in this study. 
6.6 
Treatment of Overdose 
Any dose of any study vaccine greater than the one required per protocol is considered an 
overdose. All cases of vaccine overdose should be reported as protocol deviations. Any signs 
or symptoms resulting from an overdose should be reported as AEs, or SAEs if SAE criteria 
are met; overdose per se should not be reported as an AE/SAE. GSK does not recommend 
specific treatment for an overdose; however, any resulting adverse reaction should be treated 
symptomatically. 
6.7 
Concomitant Therapy 
At each study visit/contact, the investigator or his/her delegate should question the participant 
and/or the participant’s caregiver 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 medications ongoing at screening, and all concomitant medications 
including vaccines, administered after the first dose of study intervention (Visit 1 [Day 1] 
to EoS), except vitamins and dietary supplements. 
• All concomitant medications leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (Refer to Section 5.2.2 and 
Section 9.2.1). 
• All concomitant medication which may explain/cause/be used to treat an SAE/pIMD 
including vaccines/products, as defined in Sections 8.3.1 and 10.3.6. These must also be 
recorded in the Expedited Adverse Event report. 
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• Any prophylactic medication (e.g., analgesics, antipyretics) administered on the day of 
study vaccination in the absence of any symptom and in anticipation of a reaction to the 
vaccination. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
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7.0 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific study sites or of the study as a whole are detailed in 
Section 10.1.10. 
7.1 
Discontinuation of Study Intervention 
Discontinuation of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention may 
continue other planned study procedures (e.g., safety or immunogenicity) described in the 
study protocol, at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
Table 9 
Reasons for Premature Discontinuation of Study Intervention 
Reasons 
Additional items/Sub-reasons 
AE 
Unsolicited AE  
Solicited AE 
SAEs / pIMDs  
Lost to follow-up 
- 
Withdrawal by Participant 
- 
Investigator Decision 
Specify 
Protocol Deviation 
Specify 
Site Terminated by Sponsor 
- 
Study Terminated by Sponsor 
- 
Death 
- 
Pregnancy 
- 
Other 
Specify 
 
If a participant who does not meet enrollment criteria is inadvertently enrolled, that participant 
must be discontinued from study intervention and IQVIA must be contacted. 
Participants who discontinue study intervention will not be replaced. 
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7.1.1 
Contraindications to Subsequent Study Intervention Administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose.  
Participants who meet any of the criteria listed below or criteria listed in Sections 5.2.1 and 
5.2.2 should not receive additional doses of study intervention. Such participants should be 
encouraged to continue other study procedures, at the investigator’s discretion (Section 10.3). 
All relevant criteria for discontinuation of study intervention administration must be recorded 
in the eCRF.  
• Participants who experience any SAE judged to be possibly or probably related to the 
previously administered study intervention (HZ/su vaccine or RSV investigational 
vaccine) and that, in the opinion of the investigator, may pose additional risk to the 
participant if he/she receives the subsequent study intervention (HZ/su vaccine or RSV 
investigational vaccine).  
• Participants who develop any new condition which, in the opinion of the investigator, may 
pose additional risk to the participant if he/she continues to participate in the study. 
• Anaphylaxis following the administration of study intervention(s) from Visit 1 onwards. 
• Any condition that in the judgment of the investigator would make intramuscular injection 
unsafe. 
• Pregnancy 
• Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the opinion of 
the investigator, expose the participant to unacceptable risk from subsequent vaccination. 
In such cases, the investigator should use their clinical judgment prior to administering the 
next dose of the study intervention(s). Refer to Section 10.3.3.1 for the definition of 
pIMD. 
• Participants who develop any new condition that may impair their ability to adhere to 
required study procedures. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons. This is expected to be uncommon. 
A participant is considered to have withdrawn from the study if no new study procedure has 
been performed or no new information has been collected for him/her since the date of 
withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not return 
for the concluding visit/was not available for the concluding contact planned in the protocol.  
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Investigators/site designee will attempt to contact participants who do not return for scheduled 
visits or follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact with 
the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the list 
below: 
• AEs requiring expedited reporting to IQVIA (see Appendix 3 for details regarding such 
events) 
• Unsolicited nonserious AEs 
• Solicited event 
• Withdrawal by participant, not due to an AE* 
• Migrated/Moved from the study area 
• Lost to follow-up 
• Sponsor study termination 
• Other (specify) 
*If a participant is withdrawn from the study because he/she/the participant’s caregiver(s) has 
withdrawn consent and the reason for withdrawal was provided, the investigator must 
document this reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow-up with participants who are withdrawn from the study due to an AE/SAE until the 
event is resolved (see Appendix 3 for details regarding follow-up AEs). 
7.3 
Lost to Follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled visits 
and cannot be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The study site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
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equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
• Study site personnel, or an independent third party, will attempt to collect the vital status 
of the participant within legal and ethical boundaries for all participants randomized, 
including those who did not get study intervention. Public sources may be searched for 
vital status information. If vital status is determined as deceased, this will be documented, 
and the participant will not be considered lost to follow-up. Sponsor personnel will not be 
involved in any attempts to collect vital status information. 
If the participant indicates he/she does not want to continue with the study, he/she will be 
contacted for a final assessment for safety reasons; he/she will be withdrawn from the study 
with reason of “withdrawal of consent”.  
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8.0 STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management of 
immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with IQVIA as soon as they occur or when the 
study team becomes aware of them. The purpose of this communication is to determine if the 
participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3).  
Adherence to the study design requirements, including those specified in Section 1.3, is 
essential and required for study conduct. 
All screening evaluations must be completed, and the results reviewed before confirming that 
potential participants meet all eligibility criteria. Participants who have signed informed 
consent but are not eligible to proceed should be recorded in the eCRF with a status of ‘screen 
failure’ (Section 5.4). 
If local regulations allow and quality of study procedures is maintained, participants can be 
offered remote visits (e.g., telemedicine, home visits) for the collection of biological samples 
and/or safety data/safety assessment(s). These remote visits must be performed by qualified 
study staff/healthcare professionals (HCPs). 
Following procedures can be performed remotely/virtually (refer to the Glossary of Terms for 
the definitions of telemedicine, remote and virtual visits): 
• Safety follow-up may be performed by telemedicine which will use secure video 
conferences, phone calls, and a web portal and/or mobile application (or eDiary) as a way 
of communicating with the participant and monitoring the participant’s progress. In 
addition, qualified study staff/HCPs may also identify AEs and report them to the 
investigator for evaluation.  
• Biological samples may be collected remotely by qualified study staff/HCPs. Biological 
samples should be collected only if they can be processed in a timely manner and 
appropriately stored until the intended use. 
• In exceptional situations (e.g., pandemic), the following approach may be considered: 
o If despite best efforts it is not possible to administer the dose of study intervention 
as defined in the protocol, additional 30 days may be added to the Visit 2 interval 
(only for RSV investigational vaccine administration in the Control group). 
Impact on the per protocol set (PPS) for immunogenicity will be determined on a case-by-case 
basis. 
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For information on the role of a caregiver in study assessments and procedures, please refer to 
Section 5.3. 
Procedures conducted as part of routine clinical management (e.g., hematologic profiles), and 
obtained before the participant/participant’s caregiver signed the ICF, may be used for 
screening and/or for establishing a clinical baseline (provided the procedure met protocol 
specified criteria and was performed within the time frame defined in the SoA [Section 1.3]). 
8.1 
Immunogenicity Assessments 
Biological samples will be used for research planned in the protocol and for purposes related 
to the improvement, development and quality assurance of the laboratory tests described in 
this protocol.  
Findings in this or future studies may make it desirable to use samples acquired in this study 
for research not planned in this protocol. In this case, all participants in countries where this is 
allowed will be asked to give consent to allow GSK or a contracted partner, to use the samples 
for further research. The further research will be subject to prior IEC/IRB approval, if required 
by local legislation. 
Information on further research and its rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant/participant’s caregiver.  
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 or designee.  
8.1.1 
Biological Samples 
An overall volume of approximately 30 mL of blood from each participant in the co-ad group 
and approximately 40 mL of blood from each participant in the Control group, will be 
collected during the entire study period. Refer to Table 10 for information on volumes 
collected for different assessments. 
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Table 10 
Biological Samples 
Sample type 
Quantity 
Unit 
Timepoint 
Group 
Blood for humoral response 
~10 per visit 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 4 (Day 91) 
All participants in the  
Co-ad group  
Blood for humoral response 
~10 per visit 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 3 (Day 61) 
Visit 4 (Day 91) 
All participants in the 
Control group 
Urine pregnancy test 
- 
- 
Visit 1 (Day 1) 
Visit 3 (Day 61) 
WOCBP in the Co-ad 
group 
Urine pregnancy test 
- 
- 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 3 (Day 61) 
WOCBP in the Control 
group 
Abbreviations: Co-ad=co-administration group; WOCBP=women of childbearing potential. 
8.1.2 
Laboratory Assays 
All laboratory testing will be performed at a GSK laboratory or in a laboratory designated by 
GSK. 
Table 11 
Laboratory Assays 
Assay Type 
System 
Component 
Method 
Laboratory 
Humoral 
immunity   
Serum 
RSV-A   
Neutralization 
GSK* 
RSV-B   
Neutralization 
HZ/su Anti-gE Ab 
ELISA 
Abbreviations: Ab=antibody; ELISA=enzyme linked immunosorbent assay; gE=glycoprotein E; HZ/su=herpes 
zoster/subunit; RSV-A=respiratory syncytial virus subtype A; RSV-B=respiratory syncytial virus subtype B. 
*GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. CLS 
may delegate testing to a contracted Research Organization.  
 
Refer to Section 10.2 for a brief description of the assays performed in the study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol.  
GSK clinical laboratories have established a Quality System supported by procedures. The 
activities of GSK clinical laboratories are audited regularly for quality assessment by an 
internal (Sponsor-dependent) but laboratory-independent Quality Department. 
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8.2.1 
Pre-Vaccination Procedures 
8.2.1.1 
Pregnancy Test 
Before every vaccination in this study, female participants of childbearing potential must 
perform a urine pregnancy test on the day of and before the administration of any dose of 
study intervention. Pregnancy testing must be done even if the participant is menstruating at 
the time of the study visit. The study intervention may only be administered if the pregnancy 
test is negative.  
8.2.1.2 
Collection of Demographic Data 
Record demographic data according to local regulations such as year of birth, sex, race*, and 
ethnicity* will be collected on the eCRF. Collection of sex, race and ethnicity data is 
necessary to assess and monitor the diversity of the trial participants. 
*Differences in the safety and efficacy of certain medical products, including vaccines, have 
been observed in racially and ethnically distinct subgroups.12,13,14 These differences may be 
attributable to intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., 
diet, environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 
8.2.1.3 
Medical History 
Obtain the participant’s medical history by interviewing the participant and/or review of the 
participant’s medical records. Record any relevant preexisting conditions, signs and/or 
symptoms present prior to the study intervention in the eCRF, and concomitant medications. 
8.2.1.4 
Vaccination History 
Obtain the participant’s vaccination history by interviewing the participant and/or review of 
the participant’s vaccination records. 
History of following vaccine administration should be recorded in eCRF: 
• Any vaccine administered up to 1 year before study vaccine administration (if 
possible, with the date of vaccination) 
• Live Zoster vaccine administration (if possible, with the date of vaccination) 
• COVID-19 vaccine administration (if possible, with the date of vaccination; this 
information should be collected even if administration was >1 year) 
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8.2.1.5 
Targeted Physical Examinations 
History directed/targeted physical examination will be performed for each participant on 
Visit 1 (Day 1). If the investigator determines that the participant’s health on the day of study 
intervention administration temporarily precludes dosing, the visit will be rescheduled. Refer 
to the Section 5.6 for the list of criteria for temporary delay of study intervention 
administration. 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate health 
care provider. 
Physical examination at each study visit after the study intervention administration visit, will 
be performed only if the participant/participant’s caregiver indicates during questioning that 
there might be some underlying pathology(ies) or if deemed necessary by the investigator or 
delegate. 
8.2.1.6 
Body Temperature 
The body temperature of each participant needs to be measured prior to any study intervention 
administration and recorded in the eCRF. The route for measuring temperature can be oral or 
axillary. If the participant has fever (fever is defined as temperature ≥38.0°C (100.4°F) 
regardless the location of measurement) on the day of vaccination, the vaccination visit will be 
rescheduled within the allowed interval for this visit.  
8.2.2 
Safety Contact at 6 Months Post-Last Vaccination 
Six months after the last dose of study vaccine (i.e., Month 8), each participant should be 
contacted to check if he/she has experienced any SAEs or any pIMDs since last study 
intervention administration, and to collect information on concomitant 
medications/vaccinations and pregnancy information. 
Multiple formats can be proposed by the site staff to organize these contacts. This contact may 
be done via email, text message, fax, or phone call for example. The most appropriate format 
should be agreed between site staff and the study participant. 
Text messages, email, and fax may be used as a screening to check if the participant has 
anything to report. If the participant answers "Yes" for at least one of the items of interest, a 
phone call must be done to get the details on the event(s).  
Data collected via phone calls and text messages will have to be recorded in source 
documents. E-mails and faxes can be archived in source documents. Receipt of the message 
must be confirmed by the participant or caregiver, as applicable. 
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8.2.3 
Clinical Safety Laboratory Tests 
No clinical safety laboratory tests are scheduled for this study. 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
Solicited and unsolicited AEs, SAEs and other safety reporting (pIMDs and pregnancy) are to 
be reported as indicated in this protocol; Refer to Table 1 (Co-ad group) and Table 2 (Control 
group). The administration site solicited AEs that will be collected are erythema, pain, and 
swelling. The systemic solicited AEs that will be collected are arthralgia, fatigue, fever, 
headache, myalgia, shivering/chills and gastrointestinal symptoms (nausea, vomiting, diarrhea 
and/or abdominal pain). 
Safety monitoring is specified in Figure 1 and in the endpoints (Section 3.0). 
The definitions of AEs and SAEs can be found in Appendix 3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up on AEs that are serious, considered related to the study intervention or study 
procedures, or that caused the participant to discontinue the study/study intervention (see 
Section 7.0). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
8.3.1 
Time Period and Frequency for Collecting AE, SAE, and Other Safety 
Information 
All SAEs and pIMDs will be collected from the start of study intervention until 6 months after 
the last administration of study interventions at the time points specified in the SoA 
(Section 1.3). All pregnancies beginning after the administration of the first study intervention 
until end of study will be collected at the time points specified in the SoA (Section 1.3).  
SAEs assessed as related to study participation (e.g., study intervention, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK product 
(non-investigational medicinal product) will be recorded from the time a participant consents 
to participate in the study until EoS. 
All AEs/SAEs/pIMDs/pregnancies leading to withdrawal from the study will be collected and 
recorded from the time of the first receipt of study intervention until EoS. 
All AEs will be collected in the timeframe showed in Table 13 and Table 14. 
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The investigator or designee will record and immediately report all SAEs to IQVIA via the 
Expedited AE Reporting Form. Reporting should, under no circumstances, occur later than 
24 hours after the investigator becomes aware of an SAE, as indicated in Appendix 3. The 
investigator will submit any updated SAE data to IQVIA within 24 hours of it being available.
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3Six months after the last study vaccination. 
4At Visits 1 and 3 (Co-ad group), pregnancy information must be recorded prior to study intervention administration. Pregnancies that occur post first study 
intervention will be followed as described in Section 10.4.3. 
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4 At Visits 1, 2, and 3 (Control group), pregnancy information must be recorded prior to study intervention administration. Pregnancies that occur post first study 
intervention will be followed as described in Section 10.4.3. 
 
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A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
periods defined in Table 13 and Table 14. Investigators are not obligated to actively seek 
information on AEs or SAEs after conclusion of the study participation. However, if the 
investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and he/she considers the event/cause of death to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify 
IQVIA.  
8.3.2 
Method of Detecting AEs, SAEs, Pregnancies, and Other Events 
Detecting and recording of AE/SAE/pIMDs/pregnancies are detailed in Appendix 3. 
The method of recording, evaluating, assessing intensity and causality, and outcomes of AE 
and SAE and the procedures for completing and transmitting safety reports are provided in 
Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of participants is the preferred method of acquiring 
information related to an AE/SAE/pIMD/pregnancy. 
8.3.3 
Follow-up of AEs, SAEs, pIMDs, and Pregnancies 
After the initial AE/SAE, pIMD, or pregnancy is reported, the investigator is required to 
proactively follow each participant at subsequent visits/contacts. All SAEs and pIMDs as 
defined in Section 10.3.3.1 will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is provided in Section 10.3.5. 
8.3.4 
Regulatory Reporting Requirements for SAEs, pIMDs, Pregnancies, and 
Other Events 
Once an investigator (or designee) becomes aware that a study participant has experienced an 
SAE/pIMD/pregnancy, it must be reported to IQVIA using the required documentation and 
within the timeframes mentioned in Table 15. This is essential for meeting GSK legal 
obligations and ethical responsibilities for participant safety and the safety of a study 
intervention under clinical investigation. 
For SAEs/pIMDs, the investigator must always provide an assessment of causality at the time 
of the initial report, as defined in the Appendix 3. 
Local regulatory requirements and Sponsor policy for preparation of an investigator safety 
report of Suspected Unexpected Serious Adverse Reactions (SUSAR) must be followed. 
These reports will be forwarded to investigators as necessary. 
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GSK has the legal responsibility to notify local authorities/regulatory agencies about the 
safety of an investigational study intervention. GSK will comply with country-specific 
regulatory requirements related to safety reporting to the regulatory authority, IRB/IEC, and 
investigators. 
Refer to Appendix 3 for further details regarding the reporting of SAEs/pIMDs/pregnancies. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from GSK will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Table 15 
Timeframes for Submitting SAE and Other Event Reports to IQVIA 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours*, ‡‡ 
Electronic‡ Expedited 
Adverse Events Report 
24 hours* 
Electronic‡ Expedited Adverse 
Events Report 
pIMDs 
24 hours**, ‡‡  
Electronic‡ Expedited 
Adverse Events Report 
24 hours* 
Electronic‡ Expedited Adverse 
Events Report 
Pregnancies  
24 hours**, ‡‡ 
Electronic‡ Expedited 
Adverse Events Report 
24 hours* 
 Electronic pregnancy report 
Abbreviations: pIMD=potential immune-mediated disease; SAE=serious adverse events.  
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡ Paper Expedited Adverse Events Report may be submitted in the case that the electronic Expedited Adverse 
Report system is not functioning. The paper form will be dated and signed by the investigator (or designee). 
‡‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box 
in the electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD. 
 
8.3.5 
Treatment of Adverse Events 
Any medication, vaccine or products which may explain/cause/be used to treat an SAE/pIMD 
should be recorded in the Expedited Adverse Event Report of the participant’s eCRF. 
8.3.6 
Medical Device Deficiencies 
Medical devices are being provided for use in this study as the study intervention. To fulfill 
regulatory reporting obligations worldwide, the investigator is responsible for the detection 
and documentation of events meeting the definitions of device deficiency that occur during the 
study with such devices. 
The definition of a medical device deficiency can be found in Appendix 3. 
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NOTE: Device deficiencies that lead to an AE/SAE will be reported as an AE/SAE following 
the processes outlined in Appendix 3 of the protocol.  
8.3.6.1 
Time Period for Detecting Medical Device Deficiencies 
Medical device deficiencies will be detected, documented, and reported during all periods of 
the study in which the medical device is used. 
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such a device deficiency might have led to an SAE if 
appropriate action had not been taken, intervention had not occurred, or circumstances had 
been less fortunate, the investigator will promptly notify IQVIA. 
The method of documenting medical device deficiencies is provided in Appendix 3. 
8.3.6.2 
Follow-up of Medical Device Deficiencies 
Follow-up applies to all participants, including those who discontinue study intervention. 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator. 
8.3.6.3 
Prompt Reporting of Device Deficiencies to the Sponsor 
Device deficiencies will be reported to the Sponsor or designee within 24 hours after the 
investigator determines that the event meets the protocol definition of a medical device 
deficiency. 
The medical device deficiency report form will be sent to GSK as described in Appendix 3.  
GSK will be the contact for the receipt of device deficiency reports. 
8.3.6.4 
Regulatory Reporting Requirements for Device Deficiencies 
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the Sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies. 
The investigator, or responsible person according to local requirements (e.g., the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/IEC. 
 
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8.3.7 
Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until EoS. 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor or designee within 24 hours of learning of the 
female participant pregnancy and should follow the procedures outlined in Section 10.3. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication (of 
the mother and/or neonate) or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth, or neonatal death)] the investigator will report according to the SAE 
reporting procedures described in Section 10.3. 
The participant will be followed to determine the outcome of the pregnancy (e.g., until 
delivery of baby or for longevity). The investigator will collect follow-up information on the 
participant and the neonate, and the information will be forwarded to the Sponsor or designee. 
See Table 15 for reporting timeframes. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the Sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, the investigator must report any SAE occurring as a result of a post-study 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention, to IQVIA and GSK as described in the Section 10.3.5. 
Female participants who become pregnant after the first study intervention dose must not 
receive any subsequent study interventions but may continue other study procedures at the 
discretion of the investigator. 
8.3.8 
Adverse Events of Special Interest 
Potential immune-mediated diseases are the only adverse events of special interest (AESI) 
collected during this study. See Section 10.3.3. 
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8.4 
Participant Card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to always 
keep the participant card in his/her/their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician/caregiver/family 
member that the participant is in a clinical study and that relevant information may be 
obtained by contacting the investigator or his/her backup. 
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. 
8.9 
Immunogenicity Assessments 
Immunogenicity assessments are described in Section 8.1. 
8.10 Health Economics 
Health economics parameters are not evaluated in this study. 
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9.2 
Populations for Analysis 
Populations for analyses in this study are defined in Table 17. 
Table 17 
Analysis Sets 
Analysis Set 
Description 
Screened set 
All participants who were screened for eligibility 
Enrolled set[1] 
All participants who entered the study who were randomized or received study 
intervention or underwent a post-screening study procedure.  
Exposed set  
All participants who received at least one study intervention.  
Analysis per group is based on the study intervention administered. 
RSV PPS[2] 
All eligible participants:  
• 
Who received RSV vaccine as per-protocol in the control group and received 
all the study interventions in the Co-ad group  
• 
Who had immunogenicity results pre and post-dose for RSV neutralizing 
titers  
• 
Who comply with the blood draw intervals for RSV samples 
• 
Without intercurrent medical conditions that may interfere with 
immunogenicity and without prohibited concomitant medication/vaccination 
up to blood sample post RSV vaccination for control group and blood sample 
post HZ/su vaccine dose 2 vaccination for Co-ad group 
• 
Who do not meet any of the criteria for elimination up to blood sample post 
RSV vaccination for control group and blood sample post HZ/su vaccine dose 
2 vaccination for Co-ad group 
HZ/su PPS[2] 
All eligible participants:  
• 
Who received two doses of HZ/su vaccine as per-protocol in the control 
group and all study interventions in the Co-ad group  
• 
Who had immunogenicity results pre and post-dose for anti-gE antibody 
concentrations 
• 
Who comply with the blood draw intervals for zoster samples 
• 
Without intercurrent medical conditions that may interfere with 
immunogenicity and without prohibited concomitant medication/vaccination 
up to blood sample post HZ/su vaccine dose 2 vaccination 
• 
Who do not meet any of the criteria for elimination up to blood sample post 
HZ/su vaccine dose 2 vaccination 
Abbreviations: C-ad=co-administration group; HZ/su=herpes zoster/subunit; PPS=per protocol set; 
RSV=respiratory syncytial virus. 
[1] Screen failures (who never passed screening even if rescreened) and participants screened but never enrolled 
into the study (met eligibility but not needed to reach the target enrollment) are excluded from the Enrolled 
Set as they did not enter the study 
[2] Contribution of participants to PPS will be defined by timepoint  
 
 
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9.2.1 
Criteria for Elimination 
If the participant meets one of the criteria mentioned below or any listed in the Section 7.1.1, 
(contraindication to subsequent vaccination) or Section 5.2.1 (medical conditions) or 
Section 5.2.2 (prior and concomitant therapy), he/she may be eliminated from per protocol 
analysis. 
In case of unplanned administration of any medication mentioned in Section 5.2.2 during the 
study, this will be considered as a protocol deviation and the participant may be eliminated 
from the applicable Per Protocol set (PPS). 
Participants may be eliminated from the PPS for immunogenicity if, during the study, they 
incur a condition that has the capability of altering their immune response (intercurrent 
medical condition) or are confirmed to have an alteration of their initial immune status. Refer 
to Glossary of Terms for the definition of intercurrent medical conditions. 
9.3 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and finalized before First Subject First 
Visit (FSFV). This section is a summary of the planned statistical analyses of the primary and 
secondary immunogenicity endpoints. Supportive analyses, safety and demography 
summaries will be described in the SAP. 
9.3.1 
Primary Endpoints/Estimands Analysis 
The primary endpoints are described in Section 3.0. The confirmatory analyses of 
non-inferiority will be based on the Per-Protocol set (PPS). 
• Method for non-inferiority of the HZ/su vaccine in terms of enzyme linked 
immunosorbent assay (ELISA) Ab GMC between group ratio for gE at 1-month after the 
second HZ/su vaccination (i.e., at Day 91 for both Co-ad and Control groups): 
The least square point estimate and its 2-sided 95% CI for Group GMC ratio between the 
Control group over Co-ad group will be derived from an ANCOVA model* on log10 
transformed concentrations. 
• Method for non-inferiority of RSV investigational vaccine in terms of RSV-A neutralizing 
GMT between group ratio at 1-month after the RSVPreF3 OA investigational vaccine dose 
(i.e., at Day 31 for Co-ad group, and at Day 61 for Control group): 
The least square point estimate and its 2-sided 95% CI for Group GMT ratio between 
Control group over Co-ad group will be derived from an ANCOVA model* on log10 
transformed titer. 
• Method for non-inferiority of RSV investigational vaccine in terms of RSV-B neutralizing 
GMT between group ratio at 1-month after the RSVPreF3 OA investigational vaccine dose 
(i.e., at Day 31 for Co-ad group, and at Day 61 for Control group): 
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The least square point estimate and its 2-sided 95% CI for Group GMT ratio between 
Control group over Co-ad group will be derived from an ANCOVA model* on log10 
transformed titer. 
*The model will include the treatment group and the age category (age at vaccination: 
50 to 59, 60 to 69, or 70) as fixed effects, and the pre-vaccination log10-transformed titer 
as covariate. Missing data will not be replaced. Titers below the assay cut-off will be 
replaced by half the assay cut-off; titers above the upper limit of quantification (ULOQ) 
will be replaced by the ULOQ. 
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9.3.1.1 
Success Criteria for Non-inferiority, and Testing Sequence 
The following testing sequence will be used: 
First sequence: 
• The upper limit of the 2 sided 95% CI of the GMC ratio between the Control group (at 
Day 91) versus Co-ad group (at Day 91) for anti-gE Ab 1-month after the second HZ/su 
vaccine dose is ≤1.5. 
AND 
• The upper limit of the 2 sided 95% CI of the GMT ratio between the Control group (at 
Day 61) versus Co-ad group (at Day 31) for RSV-A neutralizing titer 1-month after the 
RSVPreF3 OA investigational vaccine dose is ≤1.5. 
Second sequence: 
• The upper limit of the 2 sided 95% CI of the GMT ratio between the Control group (at 
Day 61) versus Co-ad group (at Day 31) for RSV-B neutralizing titer 1-month after the 
RSVPreF3 OA investigational vaccine dose is ≤1.5. 
Testing will progress in the second sequence only if the first sequence is a success, so that no 
further adjustment of alpha is required. 
9.3.2 
Secondary Endpoints/Estimands Analysis 
Method for evaluation of anti-gE humoral response to HZ/su vaccine when co-administered 
with RSVPreF3 OA investigational vaccine or administered separately: 
• Anti-gE antibody concentrations expressed as seropositivity rate with exact 95% CI at 
pre-vaccination and at 1-month post-second dose of HZ/su vaccine 
• Anti-gE antibody concentrations expressed as Geometric Mean Concentration (GMC) 
with 95% CI at pre-vaccination and at 1-month post-second dose of HZ/su vaccine 
• Anti-gE antibody concentrations expressed as Mean Geometric Increase (MGI) with 95% 
CI at pre-vaccination and at 1-month post-second dose of HZ/su vaccine. Definition for 
MGI is included in Table 18. 
• Vaccine response rate (VRR) with exact 95% CIs at 1-month post-second dose of HZ/su 
vaccine. Definition for VRR is included in Table 18. 
 
Method for evaluation of humoral immune response to RSVPreF3 OA investigational vaccine 
when co-administered with the first dose of HZ/su vaccine or administered separately: 
• RSV-A neutralizing titers expressed as GMT at pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose 
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• MGI for within participants ratios of the post-dose titer (at 1-month after the RSVPreF3 
OA investigational vaccine dose) over the pre-dose titer (at baseline) for RSV-A 
neutralizing titers  
• RSV-B neutralizing titers expressed as GMT at pre-vaccination and at 1-month after the 
RSVPreF3 OA investigational vaccine dose 
• MGI for within participants ratios of the post-dose titer (at 1-month after the RSVPreF3 
OA investigational vaccine dose) over the pre-dose titer (at baseline) for RSV-B 
neutralizing titers 
 
The other secondary endpoints are described in Section 3.0. Descriptive analyses of 
demography, immunogenicity, and safety will be detailed in the SAP. 
Table 18 
Definitions of Mean Geometric Increase, Vaccine Response Rate, Seropositivity 
Abbreviation/Term 
Definition 
MGI 
The geometric mean of the within participant ratios of the post-vaccination titer 
over the pre-vaccination titer. 
VRR 
For anti-gE post-second dose, is defined as the percentage of participants who 
have at least: 
A 4-fold increase post-vaccination anti-gE antibody concentration as compared 
to (over) the pre-vaccination anti-gE antibody concentration, for participants 
who are seropositive at pre-vaccination, or, 
A 4-fold increase post-vaccination anti-gE antibody concentration as compared 
to (over) the anti-gE antibody cut-off value for seropositivity (97 mIU/mL), for 
participants who are seronegative at pre-vaccination. 
Seropositivity 
Seropositivity is defined as the percentage of participants whose antibody 
concentration is greater than or equal to the assay cut-off value (97 mIU/mL). 
Abbreviations: gE=glycoprotein E; MGI=mean geometric increase; mIU/mL=milli international units per 
milliliter; VRR=vaccine response rate. 
9.4 
Interim Analysis 
9.4.1 
Sequence of Analyses 
The analyses will be performed in a stepwise manner.  
• A first analysis will be performed on all immunogenicity, reactogenicity and safety data 
available and as clean as possible, when data for at least primary and secondary endpoints 
up to and including Visit 4 (Day 91) are available for all participants. This analysis will be 
considered as final for those endpoints.  
• An EoS analysis will be performed when all data up to the contact at 6 months post-last 
vaccination will be available for all participants.  
• Any data that may become available at a later stage will be presented in additional 
analyses. 
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9.5 
Sample Size Determination 
The primary objective analysis will be performed on the PPS.  
The target enrollment will be approximately 530 participants (approximately 265 in the Co-ad 
group and approximately 265 in the Control group) to obtain approximately 450 evaluable 
participants (approximately 225 in the Co-ad group and approximately 225 in Control group) 
for the evaluation of the primary objectives, assuming that approximately 15% of the enrolled 
participants will not be evaluable (participants withdrawn or excluded from the PPS). See 
Table 19. 
Each objective will be evaluated with a nominal type I error of 2.5. 
Table 19 
Overall Power to Demonstrate Primary Non-Inferiority Objectives: Assuming 
225 Evaluable Subjects in Each Group 
Endpoint 
Standard 
deviation of 
log10 
concentration 
Reference 
ratio 
Non 
inferiority 
margin 
Type II 
error 
Power 
HZ/su vaccine Non-inferiority* (1-sided test with alpha=2.5%)  
GMCs Anti-gE 
ELISA Ab 
0.35 
1.05 
1.5 
0.3% 
99.7% 
RSVPreF3 OA investigational vaccine Non-inferiority* (1-sided test with alpha = 2.5%)  
GMTs RSV-A 
neutralizing titer  
0.45 
1.05 
1.5 
4.6% 
95.4% 
GMTs RSV-B 
neutralizing titer 
0.45 
1.05 
1.5 
4.6% 
95.4% 
Global Power and Global Type II error 
9.5% 
90.5% 
Abbreviations: Ab=antibody; ELISA=enzyme linked immunosorbent assay; gE=varicella zoster virus -
glycoprotein E; GMC=geometric mean concentration; GMT=geometric mean titer; HZ/su=herpes 
zoster/subunit; RSV-A=respiratory syncytial virus subtype A; RSV-B=respiratory syncytial virus subtype B. 
*Pass 2019 alpha = 2.5%, Two-Sample T-Tests for Non-Inferiority Assuming Equal Variance and Equal mean, 
Power = 100-the Type II error (Beta). The Global Type II error (Beta) has been adjusted using Bonferroni’s 
method (Global Type II error = sum of the individual Type II errors). 
For RSVPreF3 OA investigational vaccine: non-inferiority limit = 1.5 (log10[1.5] = 0.176) 
For HZ/su vaccine: non-inferiority limit = 1.5 (log10[1.5] = 0.176) 
Reference Ratio= 1.05 (log10[1.05] = 0.021) 
Considering a slight interference of 1.05 for the reference ratio in favor of the control group 
versus Co-ad group with a common population standard deviation of 0.45 for the log10 
transformed RSV-A/RSV-B neutralizing titer and 0.35 for the log10 transformed HZ/su 
anti-gE Ab GMC, the study has at least 90.5% power to meet the primary objectives. 
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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 International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
guidelines 
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, 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, device deficiency, 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 Sponsor or representative. 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 the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.4 
Recruitment Arrangements and Informed Consent 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’ and/or caregiver’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.  
Informed Consent Process 
• The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participants and answer all questions regarding the 
study. 
• Potential participants must be informed that their participation is voluntary. They will be 
required to physically sign a statement of informed consent that meets the requirements of 
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. 
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• The medical record must include a statement that physical informed consent was obtained 
before the participant was enrolled in the study and the date the consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A physical copy of the ICF(s) must be provided to the participant and/or their caregiver(s). 
• The participant must provide consent by signing an ICF, which summarizes the study, 
includes a consent statement and provides documentation that the participant agrees to 
continue participating in the study.  
• Participants who are rescreened are required to sign a new ICF. 
10.1.5 
Data Protection 
Participants will be assigned a unique identifier (Section 6.3.1) by the investigator. Any 
participant records or datasets transferred to GSK will contain only the identifier. Name and 
any other information which would identify the participant will not be transferred.  
GSK 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 participant/participant’s caregiver(s) must be informed that their personal 
study-related data will be used by GSK in accordance with local data protection law. The 
level of disclosure must also be explained to the caregiver(s), that the participant’s data 
will be used as described in the informed consent. 
• The participant/participant’s caregiver(s) must be informed that their medical records may 
be examined by Clinical Quality Assurance auditors or other authorized personnel 
appointed by GSK, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• 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 trusted third parties working on behalf of GSK and/or institutions working with 
GSK for the purposes of this study are contractually bound to protect participant coded 
data. GSK will protect participant coded data and will only share it as described in the 
ICF. 
The participants must be notified about their rights regarding the use of their personal data in 
accordance with the data privacy section of the ICF. 
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10.1.6 
Safety Review Team Structure 
Safety oversight will be provided by a SRT composed of GSK RSV OA project team 
members. An SRT is in place for each GSK product. It comprises of a global cross-functional 
team responsible for the ongoing assessment of benefit-risk for a product. The SRT 
contributes to the continual assessment of incoming new efficacy and safety information.  
GSK will obtain favorable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. This includes IRBs/IECs for review and approval of the 
protocol and subsequent amendments, ICF and any other documentation. 
10.1.7 
Dissemination of Clinical Study Data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with applicable 
regulations/GSK policy. GSK will aim to register 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 trial 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, including a summary of trial results understandable to 
laypersons. The investigator is encouraged to share the plain language summary results with 
the study participants, as appropriate. The full study report will be made available upon 
request, after decision on marketing authorization by regulatory authorities. 
GSK will provide the investigator with the randomization codes and participant-level line 
listings for their site only after completion of the full statistical analysis. 
GSK intends to make anonymized patient-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding. 
10.1.8 
Data Quality Assurance 
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 
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verifying that data entries are accurate and correct by physically or electronically signing 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.  
GSK or designee is responsible for the data management of this study including quality 
checking of the source data (see Glossary of Terms for the exact definition of source data).  
GSK assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations). 
Quality tolerance limits (QTLs) will be predefined in the state location(s) to identify 
systematic issues that can impact participant safety and/or the reliability of study results. 
These predefined parameters will be monitored during the study. Important deviations from 
the QTLs and remedial actions taken will be summarized in the Clinical Study Report (CSR). 
Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring, involvement of central reading 
mechanism) methods, responsibilities, and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or onsite monitoring) are 
provided in the monitoring plan. 
The Sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
Records and source documents pertaining to the conduct of this study, including signed ICFs, 
must be retained by the investigator for 25 years from issuance of the final CSR/equivalent 
summary unless local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of GSK. No 
records may be transferred to another location or party without written notification to GSK. 
10.1.9 
Source Documents 
The investigator/institution should maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study site’s participants. 
Source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, should not obscure the original entry, 
and should be explained if necessary (e.g., via an audit trail).  
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
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Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records. Also, current 
medical records must be available. 
Definition of what constitutes source data and its origin can be found in Glossary of Terms.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized study site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.10 
Study and Site Start and Closure 
First Act of Recruitment 
The start of study and the first act of recruitment are defined as first subject first visit (first 
ICF signature date) at a country-level.  
Study/Site Termination 
GSK or its designee reserves the right to close the study site or terminate the study at any time 
for any reason at its sole discretion, provided there is sufficient notice given to account for all 
participants safe exit from study.  
Regular closure of study sites will occur upon study completion. A study site is considered 
closed when all required data/documents and study supplies have been collected and a study 
site closure visit has been performed.  
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by GSK or investigator may include but are not 
limited to: 
For study termination: 
• Discontinuation of further study intervention development. 
For study site termination: 
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• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, GSK’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the investigator 
• Discontinuation of further study intervention development 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, GSK shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any Contract Research 
Organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The investigator shall promptly inform the participant 
and should assure appropriate participant therapy and/or follow-up. 
10.1.11 
Publication Policy 
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The Sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and as 
per the Sponsor’s internal policy. Authorship will be determined by mutual agreement and in 
line with International Committee of Medical Journal Editors authorship requirements. 
 
 
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10.2 Appendix 2: Clinical Laboratory Tests 
The neutralization assay is a functional assay that measures the ability of serum to neutralize 
RSV entry and replication in a host cell line. 
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of the 
test serum. The serum-virus mixture is then transferred onto a Vero cells culture (African 
Green Monkey, kidney, Cercopitheus aethiops, ATCC CCL 81) and incubated for 2 days to 
allow infection of the Vero cells by non-neutralized virus and the formation of plaques in the 
cell layer. Following a fixation step, RSV-infected cells are detected using a primary antibody 
directed against RSV (Polyclonal anti-RSV-A/B IgG) and a secondary antibody conjugated to 
horse-radish peroxidase (HRP), allowing the visualization of plaques after coloration with 
TrueBlue peroxidase substrate. 
Viral plaques are counted using an automated microscope coupled to an image analyzer 
(Scanlab system with a Reading software or equivalent). For each serum dilution, a ratio, 
expressed as a percentage, is calculated between the number of plaques at each serum dilution 
and the number of plaques in the virus control wells (no serum added). The serum neutralizing  
titer is expressed in Estimated Dilution 60 (ED60) and corresponds to the inverse of the 
interpolated serum dilution that yields a 60% reduction in the number of plaques compared to 
the virus control wells, as described by others.15,16 For the testing of Phase III studies, 
secondary standards calibrated against the international reference will be included in every run 
to allow conversion into international units.17,18 
Anti-gE ELISA is a two-step ELISA based on the antibody and antigen interaction, which 
allows the detection and the quantification of specific 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. After a washing step, goat antibodies directed against human 
IgG antibodies and conjugated to HRP (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 concentration is 
expressed in mIU/mL. 
 
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participant/participant’s caregiver(s) will be instructed to contact the study site as soon as 
possible to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant/participant’s caregiver(s) concern. Detailed 
information about reported unsolicited AEs will be collected by qualified study site 
personnel and documented in the participant’s records. 
•
Unsolicited AEs that are not medically attended nor perceived as a concern by the
participant/participant’s caregiver(s) will be collected during an interview with the
participant/participant’s caregiver(s) and by review of available medical records at the next
visit.
•
Solicited events are predefined administration site events and systemic events for which the
participant/participant’s caregiver(s) is especially questioned, and which are noted by the
participant/participant’s caregiver(s) in their eDiary. See Table 20 and Table 21 for list of
solicited site events and solicited systemic events.
o
Solicited administration site events:
Table 20 
Solicited Administration Site Events 
Pain 
Erythema/redness 
Swelling 
o
Solicited systemic events:
Table 21 
Solicited Systemic Events 
Arthralgia 
Fatigue 
Fever 
Headache 
 Myalgia 
Shivering/Chills 
Gastrointestinal symptoms: 
Nausea 
Vomiting 
Diarrhea  
Abdominal pain 
Note: participants will be instructed to measure and record their body temperature every day any 
time after 12 PM. The route for temperature measurement can be oral or axillary. If additional 
temperature measurements are taken at other times of the day, participants will be instructed to 
record their highest body temperature in the eDiary. 
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 
Medical or scientific judgment should be exercised by the investigator in deciding whether SAE 
reporting is appropriate in other situations such as significant medical events that may 
jeopardize the participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These events should usually be considered serious. 
o 
Examples of such events include invasive or malignant cancers, intensive treatment for 
allergic bronchospasm, blood dyscrasias, convulsions or development of intervention 
dependency or intervention abuse. 
SADE Definition 
 
A SADE is defined as an adverse device effect that has resulted in any of the consequences 
characteristic of an SAE. 
 
Any device deficiency that might have led to an SAE if appropriate action had not been taken, 
intervention had not occurred, or circumstances had been less fortunate. 
10.3.3 
Adverse Events of Special Interest 
Potential immune-mediated diseases are the only adverse events of special interest (AESIs) 
collected during this study. 
10.3.3.1 
Potential Immune-Mediated Diseases 
Potential immune-mediated disease is a subset of AESIs that include autoimmune diseases 
and other inflammatory and/or neurologic disorders of interest which may or may not have an 
autoimmune etiology. AEs that need to be recorded and reported as pIMDs include those 
listed in the Table 22. Please refer to Section 10.3.6 for reporting details. 
The investigator must exercise his/her medical/scientific judgment to determine whether other 
diseases have an autoimmune origin (i.e., pathophysiology involving systemic or 
organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. In addition, 
the investigator should categorize each pIMD either as a new onset condition (if it started 
following vaccination) or as an exacerbation of a preexisting chronic condition (if it 
exacerbated following vaccination) in the eCRF. In order to facilitate the documentation of 
pIMDs in the eCRF, a pIMD standard questionnaire and a list of preferred terms (PTs) and PT 
codes corresponding to the above diagnoses will be available to investigators at study start. 
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Medical Concept 
Additional Notes 
Multisystem inflammatory syndromes 
Including but not limited to: 
• 
Kawasaki’s disease 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
Includes Loefgren syndrome 
Susac's syndrome 
 
 
 
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•
Any unreturned eDiary will be sought from the participant/caregiver(s) through telephone
call(s) or any other convenient procedure.
•
Data on solicited events reported in the eDiary will be electronically transferred to the eDiary
vendor, where it can be monitored by appropriately qualified site staff and Sponsor staff
through a web-based portal. Appropriately qualified site staff should monitor eDiary data
online at frequent intervals for subject compliance and reported events that were of concern
to the subject.
•
Refer to the eDiary Manual for more information regarding the use of eDiary.
•
For device deficiencies, it is very important that the investigator describes any corrective or
remedial actions taken to prevent recurrence of the deficiency.
•
A remedial action is any action other than routine maintenance or servicing of a
medical device where such action is necessary to prevent recurrence of a device
deficiency. This includes any amendment to the device design to prevent recurrence.
•
If the site during the course of the study becomes aware of any serious, nonserious incident
(including device deficiencies and malfunctions) related to any GSK non-IMP product they
will report these events to GSK or to the concerned competent authority via the national
spontaneous reporting system.
10.3.5.1 
Time Period for Collecting and Recording AEs, SAEs, pIMDs, Pregnancies 
Time Period for Collecting and Recording AEs, SAEs, and pIMDs 
•
All solicited events that occur during 7 days following administration of the dose of study
intervention (Day 1 to Day 7) must be recorded into the eDiary, irrespective of intensity. All
other AEs occurring within this time frame should be recorded onto/into the appropriate
section of the eCRF, irrespective of their intensity or whether or not they are considered
related to the study intervention.
•
All unsolicited AEs that occur during 30 days following administration of each dose/the dose
of study intervention must be recorded onto/into the appropriate section of the eCRF,
irrespective of their intensity or whether or not they are considered related to the study
intervention.
•
SAEs related to study participation or concurrent GSK medication/vaccine will be collected
from the time a participant consents to participate in the study until the participant is
discharged from the study.
•
All other SAEs and pIMDs will be collected from the start of study intervention until
6 months after the last administration of study interventions at the time points specified in the
SoA (Section 1.3).
•
Pregnancies will be collected from the first administration of study intervention until end of
study as described in Section 10.4.3.
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activity 
 
3 
Severe: Shivering that prevents normal activity 
Gastrointestinal symptoms 
0 
None 
 
1 
Mild: Gastrointestinal symptom that is easily 
tolerated 
 
2 
Moderate: Gastrointestinal symptom that interferes 
with normal activity 
 
3 
Severe: Gastrointestinal symptom that prevents 
normal activity 
 
*Refer to the SoA (Section 1.3) for the definition of fever and the location for temperature measurement. 
The maximum intensity of injection administration site erythema/swelling and fever will be scored by 
investigator as follows: 
 
Erythema/swelling 
Fever 
0: 
≤20 mm 
<38.0 °C 
<100.4 °F 
1: 
> 20 - ≤50 mm 
≥38.0 °C (100.4 °F) - ≤38.5 °C (101.3 °F) 
2: 
> 50 - ≤100 mm 
>38.5 °C (101.3 °F) - ≤39.0 °C (102.2 °F) 
3: 
>100 mm 
>39.0 °C (102.2 °F) 
The intensity of an AE is an estimate of the relative severity of the event made by the investigator 
based on his or her clinical experience and familiarity with the literature. The following definitions 
are to be used to rate the severity of an AE: 
 
1 (Mild): A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of daily 
living. 
 
2 (Moderate): A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort but 
poses no significant or permanent risk of harm to the research participant. 
 
3 (Severe): A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
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 1 of the predefined outcomes as described in 
the Section 10.3.2. 
The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an AE (e.g., 
rated as mild, moderate, or severe, or according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events [NCI CTCAE]); the event itself may be of relatively minor 
medical significance (such as severe headache without any further findings). Severity and 
seriousness need to be independently assessed for each AE recorded on the eCRF. 
 
 
 
 
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10.4 Appendix 4: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information 
This section defines what is considered to be a woman of childbearing potential as well as 
guidance on what is considered to be adequate contraception. 
10.4.1 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal
2. Premenopausal female with 1 of the following:
a) Documented hysterectomy.
b) Documented bilateral salpingectomy.
c) Documented bilateral oophorectomy.
NOTE: Documentation can come from the study site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female:
a) A postmenopausal state is defined as no menses for 12 months without an alternative
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal
range may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy (HRT). However, in the absence of
12 months of amenorrhea, a single FSH measurement is insufficient.
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of
the non-estrogen hormonal highly effective contraception methods if they wish to
continue their HRT during the study. Otherwise, they must discontinue HRT to allow
confirmation of postmenopausal status before study enrollment.
Contraception Guidance 
10.4.2 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. 
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Table 24 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependenta  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationb  
 
Oral. 
 
Intravaginal. 
 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
 
Oral (only if allowed by local regulations or if part of standard medical practice in the country). 
 
Injectable.  
Highly Effective Methods That Are User Independenta  
Implantable progestogen only hormonal contraception associated with inhibition of ovulationb 
 
Intrauterine device. 
 
Intrauterine hormone-releasing system. 
 
Bilateral tubal occlusion. 
Vasectomized partner  
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used.  
Male partner sterilization 
Male partner sterilization prior to the female participant’s entry into the study, and this male is the sole partner 
for that participant, 
(The information on the male sterility can come from the site personnel’s review of the participant’s medical 
records; medical examination and/or semen analysis, or medical history interview provided by her or her 
partner). 
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the participant.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. 
 
See Section 8.2.1.1 for pregnancy testing information. 
10.4.3 
Collection of Pregnancy Information 
Female Participants who become pregnant  
 The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on the 
appropriate form and submitted to the Sponsor or designee within 24 hours of learning of a 
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participant’s pregnancy. The participant will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant and the 
neonate and the information will be forwarded to the Sponsor or designee. Generally, 
follow-up will not be required for longer than 6 to 8 weeks beyond the estimated delivery 
date. Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
 While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
will be reported as an AE or SAE. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (i.e., spontaneous abortion, stillbirth, neonatal death, 
or congenital anomaly [including that in an aborted fetus, stillbirth, or neonatal death]), the 
investigator will report according to the SAE reporting procedures described in 
Appendix 3. 
 Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the Sponsor or designee as described in 
Section 10.3. While the investigator is not obligated to actively seek this information in 
former participants, he or she may learn of an SAE through spontaneous reporting.  
 Any female participant who becomes pregnant after the first study intervention was 
administered must not receive any subsequent intervention (vaccinations) of any study 
intervention but may continue other study procedures at the discretion of the investigator. 
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11.0 APPENDIX 5: ABBREVIATIONS AND GLOSSARY OF 
TERMS 
Abbreviation 
Definition 
Ab 
Antibody 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANCOVA 
Analysis of Covariance 
C 
Celsius 
CBER 
Center for Biologics Evaluation and Research 
CD4 
Cluster of Differentiation 4 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMI 
Cell-mediated immunity 
Co-ad 
Co-administration group 
COVID-19 
Coronavirus disease 2019 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Regulation 
eCRF 
Electronic case report form 
DTaP 
Diphtheria-tetanus-pertussis 
EEC 
European Economic Community 
eG 
Glycoprotein E 
EoS 
End of Study 
EU 
European Union 
EUA 
Emergency use authorization 
F 
Fahrenheit 
FSFV 
First subject first visit 
GCP 
Good Clinical Practice 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline 
HCP 
Health care professional 
HZ/su 
Herpes zoster/subunit 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
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Abbreviation 
Definition 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ID 
Identification 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
LSLV 
Last subject last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGI 
Mean geometric increase 
MMSE 
Mini-Mental State Examination 
MoCA 
Montreal Cognitive Assessment 
MOPA 
Multiplexed Opsonophagocytosis 
OA 
Older adult 
pIMD 
Potential Immune-Medicated Disease 
PPS 
Per Protocol Set 
RSV 
Respiratory syncytial virus 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of activities 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
ST 
Serotype 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
UL 
Upper limit 
YOA 
Years of age 
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Table 25 
Glossary of Terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the use 
of a medicinal product, whether or not considered related to 
the medicinal product.  
An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, 
or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal 
products, this also includes failure to produce expected 
benefits (i.e., lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial 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 trial, and only 
when the data are cleaned to an acceptable level of quality 
will appropriate personnel be unblinded or when required in 
case of a serious AEs  
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned.  
Caregiver: 
A ‘caregiver’ is a person who has a continuous caring role 
for a participant or may be a person having substantial 
periods of contact with a participant and/or is engaged in 
his/her daily health care (e.g., a relative of the participant 
including family members or friends).  
In the context of this study, a caregiver can be appointed by 
the participant to oversee and support the participant’s 
compliance with protocol-specific procedures (such as 
transcribing responses to diaries, receiving phone calls, 
planning study visits, etc.). However, at no time, the 
caregiver should evaluate the participant’s health status 
while answering diaries or make decisions on behalf of the 
participant. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant: 
‘Enrolled’ means a participant’s agreement to participate in 
a clinical study following completion of the informed 
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consent process. Potential participants who are screened for 
determining eligibility for the study, but do not participate 
in the study, are not considered enrolled, unless otherwise 
specified by the protocol.  
Refer to the Section 9.2 of the protocol for the definition of 
‘enrolled set’ applicable to the study.  
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, included 
in the per-protocol analysis. 
Immunological correlate of 
protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intercurrent medical 
condition: 
A condition that has the capability of altering the immune 
response to the study vaccine or is confirmed to have an 
alteration of the participant’s initial immune status. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
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: 
A pharmaceutical form of an active ingredient being tested 
in a clinical trial, 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.  
Synonym: Investigational Medicinal Product. 
Investigator: 
A person responsible for the conduct of the clinical trial at a 
trial site. If a trial is conducted by a team of individuals at a 
trial site, the investigator is the responsible leader of the 
team and may be called the principal investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified individual 
or party to perform those trial-related duties and functions. 
Participant: 
Term used throughout the protocol to denote an individual 
who has been contacted to participate or who participates in 
the clinical study as a recipient of the study intervention 
(vaccine(s)/product(s)/control). 
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Synonym: subject. 
Randomization: 
Process of random attribution of intervention to participants 
to reduce selection bias. 
Remote visit 
This term refers to the visit conducted in the place other 
than the study site. 
Source data: 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction 
and evaluation of the trial. 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, 
laboratories and at medico-technical departments involved 
in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Telemedicine 
The use of electronic information and telecommunications 
technologies (both video-based and audio-only) to facilitate 
remote health care delivery, participant and professional 
health-related education, public health and health 
administration. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse event. 
Virtual visit 
This term refers to study visits conducted using multimedia 
or technological platforms. 
 
 
 
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12.0 REFERENCES 
 
1. GSK’s older adult respiratory syncytial virus (RSV) vaccine candidate shows 94.1% 
reduction in severe RSV disease and overall vaccine efficacy of 82.6% in pivotal trial. 
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adult-respiratory-syncytial-virus-rsv-vaccine-candidate/ 
2. Falsey AR, McElhaney JE, Beran J, et al. Respiratory syncytial virus and other 
respiratory viral infections in older adults with moderate to severe influenza-like 
illness. J Infect Dis. 2014 Jun 15;209(12):1873-81. doi: 10.1093/infdis/jit839. Epub 
2014 Jan 29. PMID: 24482398; PMCID: PMC4038137. 
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Estimates of Respiratory Syncytial Virus-Associated Acute Respiratory Infection in 
Older Adults in 2015: A Systematic Review and Meta-Analysis. J Infect Dis. 2020 Oct 
7;222(Suppl 7):S577-S583. doi: 10.1093/infdis/jiz059. PMID: 30880339. 
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Vaccine in Adults 70 Years of Age or Older. N Engl J Med. 2016; 375(11):1019-32. 
5. Cunningham AL, Heineman TC, Lal H, et al. Immune Responses to a Recombinant 
Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older. J Infect Dis. 
2018; 217(11):1750-60.  
6. López-Fauqued M, Campora L, Delannois F, et al. Safety profile of the adjuvanted 
recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. 
Vaccine. 2019; 37(18):2482-93. 
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Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory 
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Wkly Rep 2022;71:80–84. 
8. Updated Recommendations on the Use of Herpes Zoster Vaccines. National Advisory 
Committee on Immunization (NACI). Updated 27 August 2018. Accessed 07 
November 2022. https://www.canada.ca/en/services/health/publications/healthy-
living/updated-recommendations-use-herpes-zoster-vaccines.html 
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(recombinant, adjuvanted). Electronic medicines compendium (emc). Updated 16 June 
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11. Levin MJ, Oxman MN, Zhang JH, et al. Varicella-zoster virus-specific immune 
responses in elderly recipients of a herpes zoster vaccine. J Infect Dis. 2008; 
197(6):825-35. 
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12. Borchers AT, Chang C, Gershwin ME, et al. Respiratory syncytial virus – a 
comprehensive review. Clin Rev Allergy Immunol. 2013;45:331-79. 
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Vaccine Adjuvants. Front Immunol. 2013; 4:81. 
15. Barbas CF, Crowe JE, Cababa D, et al. Human monoclonal Fab fragments derived 
from a combinatorial library bind to respiratory syncytial virus F glycoprotein and 
neutralize infectivity. Proc Natl Acad Sci USA. 1992; 89(21):10164-8. 
16. Bates JT, Keefer CJ, Slaughter JC, et al. Escape from neutralization by the respiratory 
syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by 
changes in on-rate of binding to the fusion protein. Virology. 2014; 454-455: 139-44. 
17. McDonald JU, Rigsby P, Dougall T, et al. Establishment of the first WHO 
International Standard for antiserum to Respiratory Syncytical Virus: Report of an 
International collaborative study. Vaccine.2018; 36: 7641-7649.  
18. McDonald JU, Rigsby P, Atkinson E, et al. Expansion of the 1st WHO international 
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against RSV subtype B: An international collaborative study. Vaccine. 2020; 38: 
800-807. 
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Signature of Investigator 
PROTOCOL TITLE: A Phase III, open-label, randomized, controlled, multi-country study to 
evaluate the immune response, safety and reactogenicity of RSVPreF3 OA investigational 
vaccine when co-administered with Herpes Zoster recombinant subunit (HZ/su) vaccine in 
adults aged 50 years and older. 
PROTOCOL NO: 
219331 (RSV OA=ADJ-020) 
VERSION:  
 
Original Protocol 
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 
Sponsor. 
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:               
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________ 
 
 
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