A Phase 1, Observer-blind, Randomized, Placebo-Controlled Study to Evaluate Reactogenicity, Safety and Immune Response of an HSV-targeted Immunotherapy in HSV-2 Seronegative Japanese Participants Aged 18-40 Years
Phase: PHASE1
Conditions: Herpes Simplex
Sponsor: GlaxoSmithKline

 

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218459 (TH HSV REC-004) 
Protocol Final 
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1 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut, 89 
1330 Rixensart, Belgium
Primary study intervention 
GSK investigational HSV-targeted immunotherapy 
(GSK3943104A) 
Other study intervention 
Placebo (sodium chloride) 
Study number and 
abbreviated title 
218459 (TH HSV REC-004) 
Date of protocol 
Final: 16 March 2023 
Title 
A Phase 1, observer-blind, randomized, 
placebo‑controlled study to evaluate reactogenicity, 
safety and immune response of an HSV-targeted 
immunotherapy in HSV-2 seronegative Japanese 
participants aged 18-40 years. 
Brief title 
A study on the reactogenicity, safety and immune 
response of a targeted immunotherapy against HSV 
in healthy Japanese participants aged 18-40 years. 
Sponsor signatory 
Lan Lin, 
Clinical Project Lead, 
Vaccines Clinical Science 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.3 
©2023 GSK group of companies or its licensor. 

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

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

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Study number and 
abbreviated title 
218459 (TH HSV REC-004) 
Date of protocol 
Final: 16 March 2023 
Title 
A Phase 1, observer-blind, randomized, 
placebo‑controlled study to evaluate reactogenicity, 
safety and immune response of an HSV-targeted 
immunotherapy in HSV-2 seronegative Japanese 
participants aged 18-40 years. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
GSK Japan study 
representative, function and 
title 
 
, Clinical Development (Vaccine), Vaccine 
Medical and Development, Japan Medical & 
Development, GlaxoSmithKline K. K. 
 
 
Signature 
 
 
 
Date of signature 
 
 
 
PPD
PPD

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218459 (TH HSV REC-004) 
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16 March 2023 
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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to the local study contact information document. 
4. Sponsor study contact for reporting of SAEs 
GSK central back-up study contact for reporting SAEs: refer to Section 8.3.3.1.  
Study contact for reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for emergency unblinding 
Refer to Section 6.3.4.1. 
 

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 5 
1. 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1. 
Synopsis ..................................................................................................... 13 
1.2. 
Schema ...................................................................................................... 14 
1.3. 
Schedule of Activities .................................................................................. 15 
2. 
INTRODUCTION .................................................................................................... 18 
2.1. 
Background ................................................................................................ 18 
2.2. 
Study rationale ............................................................................................ 19 
2.3. 
Benefit/Risk Assessment ............................................................................ 19 
2.3.1. 
Risk assessment .......................................................................... 20 
2.3.2. 
Benefit assessment ..................................................................... 21 
2.3.3. 
Overall benefit/risk assessment ................................................... 21 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ................................................... 22 
4. 
STUDY DESIGN .................................................................................................... 23 
4.1. 
Overall design ............................................................................................. 23 
4.2. 
Scientific rationale for study design ............................................................. 25 
4.3. 
Justification for dose ................................................................................... 25 
4.4. 
End of Study definition ................................................................................ 25 
5. 
STUDY POPULATION ........................................................................................... 25 
5.1. 
Inclusion criteria .......................................................................................... 25 
5.2. 
Exclusion criteria ......................................................................................... 26 
5.2.1. 
Medical conditions ....................................................................... 26 
5.2.2. 
Prior/Concomitant therapy ........................................................... 27 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 28 
5.2.4. 
Other exclusions .......................................................................... 28 
5.3. 
Lifestyle considerations ............................................................................... 28 
5.4. 
Screening failures ....................................................................................... 28 
5.5. 
Criteria for temporarily delaying enrolment/study intervention 
administration ............................................................................................. 28 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 29 
6.1. 
Study interventions administered ................................................................ 30 
6.2. 
Preparation, handling, storage, and accountability ...................................... 31 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 31 
6.3.1. 
Participant identification ............................................................... 31 
6.3.2. 
Randomization to study intervention ............................................ 31 
6.3.3. 
Intervention allocation to the participant ....................................... 31 
6.3.4. 
Blinding and unblinding ................................................................ 32 
6.3.4.1. 
Emergency unblinding ................................................ 32 
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs ......... 33 
6.4. 
Study intervention compliance .................................................................... 33 
6.5. 
Dose modification ....................................................................................... 33 
6.6. 
Continued access to study intervention after the end of the study ............... 33 
6.7. 
Treatment of overdose ................................................................................ 33 

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6.8. 
Concomitant therapy ................................................................................... 33 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 34 
7.1. 
Discontinuation of study intervention ........................................................... 34 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 34 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 35 
7.3. 
Lost to follow-up .......................................................................................... 36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 36 
8.1. 
Immunogenicity assessments ..................................................................... 37 
8.1.1. 
Biological samples ....................................................................... 38 
8.1.2. 
Laboratory assays ....................................................................... 38 
8.1.3. 
Immunological read-outs .............................................................. 39 
8.1.4. 
Immunological correlates of protection ......................................... 40 
8.2. 
Safety assessments .................................................................................... 40 
8.2.1. 
Pre-intervention administration procedures .................................. 40 
8.2.1.1. 
Collection of demographic data .................................. 40 
8.2.1.2. 
Measure and record height and weight ....................... 40 
8.2.1.3. 
Medical and vaccination history .................................. 40 
8.2.1.4. 
Perform physical examination ..................................... 40 
8.2.1.5. 
Perform pregnancy test .............................................. 41 
8.2.2. 
Clinical safety laboratory tests ..................................................... 41 
8.2.3. 
Study holding rules and safety monitoring .................................... 41 
8.2.3.1. 
Study Holding Rules ................................................... 42 
8.2.3.2. 
Outcome of Safety Evaluation .................................... 44 
8.3. 
Adverse Events, Serious Adverse Events and other safety reporting .......... 46 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 46 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 47 
8.3.2.1. 
Clinically significant abnormal laboratory 
findings ....................................................................... 47 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies 
and other events .......................................................................... 47 
8.3.3.1. 
Contact information for reporting SAEs, pIMDs, 
pregnancies and study holding rules .......................... 49 
8.3.4. 
Treatment of expedited adverse events (SAE/pIMD) ................... 49 
8.3.5. 
Participant card ............................................................................ 49 
8.3.6. 
Safety follow-up call ..................................................................... 49 
8.4. 
Pharmacokinetics ....................................................................................... 49 
8.5. 
Genetics ..................................................................................................... 50 
8.6. 
Biomarkers ................................................................................................. 50 
8.7. 
Immunogenicity assessments ..................................................................... 50 
8.8. 
Health outcomes ......................................................................................... 50 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 50 
9.1. 
Statistical hypotheses ................................................................................. 50 
9.2. 
Analysis sets ............................................................................................... 51 
...................................... 51 
9.3. 
Statistical analyses ..................................................................................... 51 
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9.3.1. 
Participants Disposition ................................................................ 52 
9.3.2. 
Demography and Baseline Characteristics Analyses ................... 52 
9.3.3. 
Primary Endpoints/Estimands Analyses ....................................... 53 
9.3.4. 
Secondary Endpoints/Estimands Analyses .................................. 54 
9.3.5. 
Tertiary Endpoints/Estimands Analyses ....................................... 55 
9.4. 
Sequence of analyses ................................................................................. 55 
9.5. 
................................................................. 55 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 56 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 56 
10.1.1. 
Regulatory and ethical considerations ......................................... 56 
10.1.2. 
Financial disclosure ..................................................................... 57 
10.1.3. 
Informed consent process ............................................................ 57 
10.1.4. 
Data protection ............................................................................ 58 
10.1.5. 
Committees structure ................................................................... 58 
10.1.6. 
Dissemination of clinical study data ............................................. 59 
10.1.7. 
Data quality assurance ................................................................ 59 
10.1.8. 
Source documents ....................................................................... 60 
10.1.9. 
Study and site start and closure ................................................... 60 
10.1.10. Publication policy ......................................................................... 61 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 62 
10.2.1. 
Laboratory Assays Description .................................................... 62 
10.2.2. 
Protocol required safety laboratory assessments ......................... 65 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 66 
10.3.1. 
Definition of an adverse event (AE) .............................................. 66 
10.3.1.1. Events Meeting the AE Definition ............................... 66 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 66 
10.3.2. 
Definition of an SAE ..................................................................... 67 
10.3.3. 
Solicited events ............................................................................ 68 
10.3.4. 
Unsolicited AEs ............................................................................ 68 
10.3.5. 
SAEs related to Study Participation ............................................. 69 
10.3.6. 
Adverse events of special interest ................................................ 69 
10.3.6.1. Potential immune-mediated diseases ......................... 69 
10.3.7. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 75 
10.3.8. 
Events or outcomes not qualifying as AEs or SAEs ..................... 75 
10.3.8.1. Pregnancy .................................................................. 75 
10.3.9. 
Recording and follow-up of AEs, SAEs, pIMDs and 
pregnancies ................................................................................. 75 
10.3.9.1. Time period for collecting and recording AEs, 
SAEs, pIMDs and pregnancies ................................... 76 
10.3.9.2. Follow-up of AEs, SAEs, pIMDs, pregnancies 
or any other events of interest .................................... 77 
10.3.9.2.1. Follow-up during the study ...................... 77 
10.3.9.2.2. Follow-up after the participant is 
discharged from the study....................... 77 
10.3.9.2.3. Follow-up of pregnancies ........................ 77 
10.3.9.3. Updating of SAE, pIMD and pregnancy 
information after removal of write access to the 
participant’s eCRF ...................................................... 78 
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10.3.10. Assessment of intensity and causality .......................................... 78 
10.3.10.1. Assessment of intensity .............................................. 78 
10.3.10.2. Assessment of causality ............................................. 79 
10.3.10.3. Medically attended visits ............................................. 80 
10.3.10.4. Assessment of outcomes ............................................ 81 
10.3.11. Reporting of SAEs, pIMDs, pregnancies and other events ........... 81 
10.3.11.1. Events requiring expedited reporting to GSK .............. 81 
10.3.11.2. Back-up system in case the electronic reporting 
system does not work ................................................. 81 
10.4. 
Appendix 4: Contraceptive guidance and collection of pregnancy 
information .................................................................................................. 82 
10.4.1. 
Definitions .................................................................................... 82 
10.4.1.1. Woman of childbearing potential ................................. 82 
10.4.1.1.1. Women not considered as women 
of childbearing potential .......................... 82 
10.4.2. 
Contraception guidance ............................................................... 82 
10.4.3. 
Collection of pregnancy information ............................................. 83 
10.4.3.1. Female participants who become pregnant ................ 83 
10.5. 
Appendix 5: Genetics .................................................................................. 83 
10.6. 
Appendix 6: Definition of medical device AE, adverse device effect, 
serious adverse device effect and unanticipated SADE .............................. 84 
10.7. 
Appendix 7: Country-specific requirements ................................................. 84 
10.7.1. 
Regulatory and ethical considerations ......................................... 84 
10.7.2. 
Study administrative structure ...................................................... 84 
10.7.3. 
Unapproved medical device ......................................................... 84 
10.8. 
Appendix 8: Abbreviations and glossary of terms ........................................ 85 
10.8.1. 
List of abbreviations ..................................................................... 85 
10.8.2. 
Glossary of terms ......................................................................... 88 
11. REFERENCES ....................................................................................................... 93 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 15 
Table 2 
Intervals Between Study Visits ............................................................... 17 
Table 3 
Study objectives, endpoints and estimands ............................................ 22 
Table 4 
Study groups, intervention and blinding .................................................. 25 
Table 5 
Study interventions administered ........................................................... 30 
Table 6 
Contact information for emergency unblinding ....................................... 33 
Table 7 
Biological samples ................................................................................. 38 
Table 8 
Laboratory assays .................................................................................. 38 
Table 9 
Immunological read-outs ........................................................................ 39 
Table 10 
Study Holding Rules ............................................................................... 43 
Table 11 
Timeframes for collecting and reporting of safety information ................. 46 
Table 12 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 48 
Table 13 
Contact information for reporting SAEs, AESIs, pregnancies and 
study holding rules ................................................................................. 49 
Table 14 
Analysis sets .......................................................................................... 51 
.... 55 
.... 56 
Table 17 
Hematology and Biochemistry Read-Outs .............................................. 65 
Table 18 
Toxicity Grading Scales for Hematology and Biochemistry 
Parameters Applicable for this Study ...................................................... 65 
Table 19 
Solicited administration site events ......................................................... 68 
Table 20 
Solicited systemic events ....................................................................... 68 
Table 21 
List of potential immune-mediated diseases (pIMDs) ............................. 69 
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Table 22 
Intensity scales for solicited events ........................................................ 78 
Table 23 
Intensity Scales for Unsolicited AEs ....................................................... 79 
Table 24 
Highly effective contraceptive methods .................................................. 83 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 24 
Figure 2 
Risk Assessment Curves for Study Holding Rules ................................. 44 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale:  
Infections caused by HSV types 1 and 2 (HSV-1 and HSV-2) are frequent and affect 
people of every race, sex, age, and social status [Berger, 2008; Looker, 2008]. Using a 
pooled analysis, James et al. estimated that approximately 491.5 million people 
worldwide aged 15 to 49 years were infected with HSV-2 (which is equivalent to a global 
prevalence of 13.2% in this age population) and an estimated 23.9 million are new 
infections each year (which is equivalent to a global incidence of 0.6%) [James, 2020]. 
More women are infected than men, probably due to their greater biological susceptibility 
to HSV-2. Prevalence increases also with age, as infection is lifelong [Wald, 2004]. In the 
Fukuoka prefecture, the sera of 1244 subjects (574 men and 670 women) in the general 
population were screened for IgG antibodies against HSV by ELISA [Doi, 2009]. The 
seroprevalence of HSV-1 and HSV-2 were 59.7% and 8.4%, respectively. By sex, the 
seroprevalence of HSV-1 and HSV-2 was 55.4% and 7.4% in men and 63.3% and 9.3% 
in women, respectively. Of note, the study was conducted on a geographically limited 
population and may not be representative of the entire Japanese population. An 
international comparison of HSV-1 and HSV-2 seroprevalences revealed that the 
seroprevalence of HSV-1 in Japan is similar to those reported in other industrialized 
countries; whilst the seroprevalence of HSV-2 in Japan (4.4-11.1%) was comparable with 
the one reported in some European countries (4%–14%), but lower than in the United 
States (22%) [Doi, 2009]. 
HSV-1 and HSV-2 infections manifest in various forms, from asymptomatic to clinical 
presentations such as oral herpes or herpes labialis (‘cold sores’) and genital herpes. Both 
viruses infect epithelial cells at skin or mucosal surfaces (e.g., orolabial mucosa, genital 
mucosa) and then infect nerve endings, traveling via retrograde transport to the nerve 
axon, where they establish persistent infection in the trigeminal or lumbosacral ganglia. 
Reactivation can occur throughout a person’s life: the virus returns to epithelial surfaces 
via the axon to cause either oral or genital ulcers/lesions or asymptomatic viral shedding 
[Belshe, 2012]. In addition, it is known that infections with HSV-1 and HSV-2 may result 
in blindness, encephalitis and neonatal infections. The ability of the virus to be 
transmitted in the absence of symptoms, or when lesions are unnoticed, contributes to the 
spread throughout the population. 
With the burden of the disease as described above and the limitations of antiviral 
therapies (e.g., daily intake in case of suppressive therapy, antiviral resistance in 
immunocompromised patients, limited impact on transmission [Corey, 2004] and no 
benefit in terms of the risk of acquisition or transmission of HIV-1 [Freeman, 2006]), 
there is still a high medical need globally for an improved treatment. HSV-2 infections 
are lifelong, incurable, stigmatizing and no existing interventions can effectively prevent 
them at population level [Gottlieb, 2019]. 
 
 
 
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GSK is developing a new investigational HSVTI 
 
. In the ongoing Phase 1/2 study (TH HSV 
REC-003), 2 formulations have been selected based on the safety, reactogenicity and 
immunogenicity data 1 month post-Dose 2 for proof-of-concept evaluation.  
The purpose of the current study is to assess the safety, reactogenicity and 
immunogenicity of the 2 selected formulations in ethnic Japanese adults aged 18-40 
years. 
 
 
Objectives, endpoints and estimands: 
Refer to Table 3. 
 
1.2. 
Schema 
Refer to Figure 1. 
 
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1.3. 
Schedule of Activities 
Table 1 
Schedule of Activities 
Type of Contact 
Screening Study Intervention Administration Phase 
Follow-up 
Phase 
Screening* 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Phone call 
Timepoints 
Day -56 
Day 1 
Day 8 
Day 29 
Day 36 
Day 57 
Day 209 
Obtain informed consent (Section 10.1.3) 
● 
 
 
 
 
 
 
Check inclusion/exclusion criteria (Sections 5.1 and 5.2) 
● 
● 
 
 
 
 
 
Collect demographic data (Section 8.2.1.1) 
● 
 
 
 
 
 
 
Measure and record height and weight (Section 8.2.1.2) 
● 
 
 
 
 
 
 
Record medical and vaccination history (Section 8.2.1.3) 
● 
 
 
 
 
 
 
Perform physical examination (Section 8.2.1.4) 
● 
● 
○ 
● 
○ 
○ 
 
Perform pregnancy test (Section 8.2.1.5) 
● 
●** 
 
●** 
 
 
 
Record pre-study intervention administration body temperature*** 
 
● 
 
● 
 
 
 
Study group randomization (Section 6.3.2) 
 
○ 
 
 
 
 
 
Study intervention number allocation (Section 6.3.3) 
 
● 
 
● 
 
 
 
Check contraindications to subsequent study intervention administration (Section 
7.1.1) 
 
 
 
● 
 
 
 
Study intervention administration and recording of administered study intervention 
number (Section 6.1) 
 
● 
 
● 
 
 
 
Blood sampling for HSV testing (3.5 mL) (Section 8.1.1) 
○ 
 
 
 
 
 
 
Blood sampling for hematology analysis (2.0 mL) (Section 8.1.1) 
● 
●** 
● 
●** 
● 
● 
 
Blood sampling for biochemical analysis (3.5 mL) (Section 8.1.1) 
● 
●** 
● 
●** 
● 
● 
 
Blood sampling for antibody determination (humoral immune response) (8.5 mL) 
(Section 8.1.1) 
 
○** 
 
○** 
 
○ 
 
Blood sampling (PBMC) for CMI response analysis (30.0 mL) (see Section 8.1.1) 
 
○** 
 
○** 
 
○ 
 
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Type of Contact 
Screening Study Intervention Administration Phase 
Follow-up 
Phase 
Screening* 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Phone call 
Timepoints 
Day -56 
Day 1 
Day 8 
Day 29 
Day 36 
Day 57 
Day 209 
Distribution of ‘Participant card’ (Section 8.3.5) 
○ 
 
 
 
 
 
 
Distribution of paper diary cards (Section 10.3.9) 
 
○ 
 
○ 
 
 
 
Return of paper diary cards (Section 10.3.9) 
 
 
○ 
○ 
○ 
○ 
 
Diary card transcription by investigator or delegate (Section 10.3.9) 
 
 
● 
● 
● 
● 
 
Record any concomitant medications/vaccinations (Section 6.8) 
● 
● 
● 
● 
● 
● 
● 
Record intercurrent medical conditions leading to elimination from analysis (Section 
9.2.1) 
● 
● 
● 
● 
● 
● 
● 
Recording of solicited AEs (Days 1 to 7 post-each study intervention administration) 
(Section 10.3.9) 
 
● 
● 
● 
● 
 
 
Recording of unsolicited AEs (Days 1 to 28 post-each study intervention 
administration) (Section 10.3.9) 
 
● 
● 
● 
● 
● 
 
Recording of MAEs (Section 8.3) 
 
● 
● 
● 
● 
● 
● 
Recording of SAEs (Section 8.3) 
 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study participation or to a concurrent GSK 
medication/vaccine (Section 8.3) 
● 
● 
● 
● 
● 
● 
● 
Recording of pIMDs (Section 8.3) 
 
● 
● 
● 
● 
● 
● 
Recording of AEs leading to withdrawal from the study intervention or withdrawal from 
study (Section 7) 
 
● 
● 
● 
● 
● 
● 
Recording of pregnancies and pregnancy outcome (Section 8.3) 
 
● 
● 
● 
● 
● 
● 
Study conclusion (Section 4.4) 
 
 
 
 
 
 
● 
AE: adverse event; CMI: cell-mediated immunity;
 MAE: medically attended event; PBMC: peripheral blood 
mononuclear cell; pIMD: potential immune-mediated disease; SAE: serious adverse event. 
Note: The double-line borders indicate the analyses which will be performed on all data obtained up to these timepoints (refer to Section 9.3.5). 
● is used to indicate a study procedure that requires documentation in the individual electronic Case Report Form (eCRF). 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
* Screening evaluations may be completed up to 56 days before Visit 1 (Day 1). Study staff should allow sufficient time between the Screening visit and Visit 1 to receive and review 
HSV testing results, and hematology/biochemical results. If deemed necessary by the investigator, re-testing can be performed within the allowed interval. Only data from the re-
sampling testing, if done, will be taken into consideration. 
** Blood sampling and pregnancy test to be performed before each study intervention administration. 
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*** The preferred location for measuring temperature will be the oral cavity. Study intervention administration should not occur in case of fever (defined as temperature≥ 38.0°C, 
regardless of the location of measurement). 
# Optional blood sampling. A separate informed consent form (ICF) will be signed by participants who agree to give their blood sample for this optional blood sampling. 
Table 2 
Intervals Between Study Visits 
Interval 
Reference Visits 
Planned Visit Interval 
Allowed Interval Range 
Screening (Day -56) → Visit 1 (Day 1) 
Screening visit 
Up to 56 days* 
Visit 1 (Day 1) → Visit 2 (Day 8) 
Study intervention administration 
Dose 1 
7 days 
7 – 9 days 
Visit 1 (Day 1) → Visit 3 (Day 29) 
 
28 days 
28 – 33 days** 
Visit 3 (Day 29) → Visit 4 (Day 36) 
Study intervention administration 
Dose 2 
7 days 
7 – 9 days 
Visit 3 (Day 29) → Visit 5 (Day 57) 
 
28 days 
28 – 33 days** 
Visit 3 (Day 29) → Phone call (Day 209) 
 
180 days 
173 – 187 days 
* Screening evaluations may be completed up to 56 days before Visit 1 (Day 1). Study staff should allow sufficient time between the Screening visit and Visit 1 to receive and review 
HSV testing results and hematology/biochemical results. 
** Visits out of the allowed interval can lead to elimination from the Per Protocol set for analysis of immunogenicity. 
 

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2. 
INTRODUCTION 
2.1. 
Background 
Infections caused by HSV types 1 and 2 (HSV-1 and HSV-2) are frequent and affect 
people of every race, sex, age, and social status [Berger, 2008; Looker, 2008]. Using a 
pooled analysis, James et al. estimated that approximately 491.5 million people 
worldwide aged 15 to 49 years were infected with HSV-2 (which is equivalent to a global 
prevalence of 13.2% in this age population) and an estimated 23.9 million are new 
infections each year (which is equivalent to a global incidence of 0.6%) [James, 2020]. 
More women are infected than men, probably due to their greater biological susceptibility 
to HSV-2. Prevalence increases also with age, as infection is lifelong [Wald, 2004]. In the 
Fukuoka prefecture, the sera of 1244 subjects (574 men and 670 women) in the general 
population were screened for IgG antibodies against HSV by ELISA [Doi, 2009]. The 
seroprevalence of HSV-1 and HSV-2 were 59.7% and 8.4%, respectively. By sex, the 
seroprevalence of HSV-1 and HSV-2 was 55.4% and 7.4% in men and 63.3% and 9.3% 
in women, respectively. Of note, the study was conducted on a geographically limited 
population and may not be representative of the entire Japanese population. An 
international comparison of HSV-1 and HSV-2 seroprevalences revealed that the 
seroprevalence of HSV-1 in Japan is similar to those reported in other industrialized 
countries; whilst the seroprevalence of HSV-2 in Japan (4.4-11.1%) was comparable with 
the one reported in some European countries (4%–14%), but lower than in the United 
States (22%) [Doi, 2009]. 
HSV-1 and HSV-2 infections manifest in various forms, from asymptomatic to clinical 
presentations such as oral herpes or herpes labialis (‘cold sores’) and genital herpes. Both 
viruses infect epithelial cells at skin or mucosal surfaces (e.g., orolabial mucosa, genital 
mucosa) and then infect nerve endings, traveling via retrograde transport to the nerve 
axon, where they establish persistent infection in the trigeminal or lumbosacral ganglia. 
Reactivation can occur throughout a person’s life: the virus returns to epithelial surfaces 
via the axon to cause either oral or genital ulcers/lesions or asymptomatic viral shedding 
[Belshe, 2012]. In addition, it is known that infections with HSV-1 and HSV-2 may result 
in blindness, encephalitis and neonatal infections. The ability of the virus to be 
transmitted in the absence of symptoms, or when lesions are unnoticed, contributes to the 
spread throughout the population. 
The affected age groups and severity of infection are influenced by the infecting virus 
type, the site of infection, host immune status, and whether the infection is initial or 
recurrent. Most recurrent genital herpes are caused by HSV-2, while HSV-1 infections 
are typically orolabial and acquired during childhood [Bradley, 2014; Johnston, 2016]. 
However, in industrialized countries, HSV-1 genital infections appear to be the leading 
cause of primary episode genital herpes among young adults [Roberts, 2003; Ryder, 
2009; Bernstein, 2013; Johnston, 2016]. 
With the burden of the disease as described above and the limitations of antiviral 
therapies (e.g., daily intake in case of suppressive therapy, antiviral resistance in 
immunocompromised patients, limited impact on transmission [Corey, 2004] and no 
benefit in terms of the risk of acquisition or transmission of HIV-1 [Freeman, 2006]), 

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there is still a high medical need globally for an improved treatment. HSV-2 infections 
are lifelong, incurable, stigmatizing and no existing interventions can effectively prevent 
them at population level [Gottlieb, 2019]. 
 
 
 
GSK is developing a new investigational HSVTI 
 
 In the ongoing Phase 1/2 study (TH 
HSV REC-003), 2 formulations have been selected based on the safety, reactogenicity 
and immunogenicity data 1 month post-Dose 2 for proof-of-concept evaluation.  
The purpose of the current study is to assess the safety, reactogenicity and 
immunogenicity of the 2 selected formulations in ethnic Japanese adults aged 18-40 
years. 
 
. 
2.2. 
Study rationale 
Please refer to the current IB for information regarding pre-clinical, clinical and studies 
of the HSVTI. 
The intention of this study is to enable Japanese population to participate in the global 
Phase 3 study. The purpose of this study in Japan is to evaluate the safety, reactogenicity, 
and immunogenicity of 2 formulations of HSVTI (
) in HSV-2 seronegative 
ethnic Japanese adults aged 18-40 years. 
2.3. 
Benefit/Risk Assessment 
Detailed information about the known and expected benefits and risks, and expected AEs 
of 
 can be found in the IB. 
 
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2.3.1. 
Risk assessment 
The risk assessment and mitigation strategy for this study are outlined in the table below: 
Important / Potential / Identified / 
Risk of Clinical Significance 
Summary of Data / Rationale for Risk 
Mitigation Strategy 
  
Hypersensitivity including allergic 
reaction such as anaphylaxis 
Acute allergic reactions such as a rare case of anaphylactic 
event may occur with any vaccine administration. These are 
serious, but rare occurrences are estimated in the range of 1 to 
10 cases per million of vaccinations, depending on the vaccine 
studied [Ruggerberg, 2007]. 
Participants with known hypersensitivity to any component of the study 
intervention are excluded from enrolment. The onset of study 
intervention-related allergic symptoms occurs shortly after study 
intervention administration. In order to treat participants with a serious 
allergic reaction to study intervention, all participants will need to remain 
under observation (i.e., visibly followed, no specific procedure) at the 
study site for at least 60 minutes after study intervention administration. 
Potential immune-mediated 
diseases 
pIMDs are a theoretical concern with adjuvanted vaccines 
[Tavares, 2013]. 
During the informed consent process, participants will be informed of this 
theoretical risk and asked to report any AEs that they consider 
serious/significant and/or for which they received medical attention at 
any point during the study. 
A pIMD is an AE of special interest and occurrence of pIMDs will be 
captured and described. All pIMDs will be collected up to 6 months after 
administration of the last dose of study intervention. 
Study Procedures 
Pain and bruising 
Pain or bruising at the site where blood is drawn. 
Blood samples will be obtained by a trained professional and medical 
assistance will be available. 
Syncope 
Syncope (fainting) can occur following or even before any 
vaccination as a psychogenic response to the needle injection. 
All participants will remain under observation at the study site for at least 
60 minutes after study intervention administration. 
AE: adverse event; 
 pIMD: potential immune-mediated disease. 
 
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2.3.2. 
Benefit assessment 
Participants may gain information and medical advice about their general health status 
through medical evaluations/assessments associated with this study (i.e., physical 
examinations and blood testing [hematology and biochemistry data]). 
2.3.3. 
Overall benefit/risk assessment 
 is currently in a very early stage of clinical development and no efficacy has 
been demonstrated in humans yet. Considering the measures taken to minimize the risk to 
participants taking part in this study, the potential risks identified in association with the 
 are justified by the potential benefits linked to the development of the study 
intervention. 
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3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
Table 3 
Study objectives, endpoints and estimands  
Objectives 
Endpoints and estimands 
Primary 
To evaluate the reactogenicity and safety of the HSVTI. 
• 
Percentage of participants reporting each solicited 
administration site event (redness, pain, and swelling) 
within 7 days (Day 1-Day 7) post-each dose. 
• 
Percentage of participants reporting each solicited 
systemic event (fever, fatigue, headache, myalgia, 
arthralgia) within 7 days (Day 1-Day 7) post-each 
dose. 
• 
Percentage of participants reporting unsolicited AEs 
within 28 days (Day 1-Day 28) post-each dose. 
• 
Percentage of participants reporting MAEs from Dose 
1 (Day 1) up to 28 days post-Dose 2 (Day 57). 
• 
Percentage of participants reporting SAEs from Dose 
1 (Day 1) up to 28 days post-Dose 2 (Day 57). 
• 
Percentage of participants reporting newly diagnosed 
pIMDs from Dose 1 (Day 1) up to 28 days post-Dose 
2 (Day 57). 
• 
Percentage of participants reporting exacerbation of 
pre-existing pIMDs from Dose 1 (Day 1) up to 28 days 
post-Dose 2 (Day 57). 
• 
Percentage of participants reporting any 
hematological and biochemical laboratory 
abnormalities at pre-study intervention administration 
(Day 1), post-Dose 1 (Day 8 and Day 29), and post-
Dose 2 (Day 36 and Day 57). 
Secondary 
To evaluate the humoral immune response induced by the 
HSVTI.  
• 
 antibody GMC and seropositivity 
rate (assessed by ELISA) at pre-study intervention 
administration (Day 1), 28 days post-Dose 1 (Day 29), 
and 28 days post-Dose 2 (Day 57). 
To evaluate the cellular immune response induced by the 
HSVTI. 
• 
Geometric mean of 
 CD4+/CD8+ T-cells 
frequency expressing at least 2 activation markers 
(IFN-, TNF-, IL-2, IL-13, IL-17, 4-1BB and/or 
CD40L) and including at least one cytokine (assessed 
by CFC) at pre-study intervention administration (Day 
1), 28 days post-Dose 1 (Day 29) and 28 days post-
Dose 2 (Day 57). 
To evaluate the safety of the HSVTI up to the end of 
follow-up period.  
• 
Percentage of participants reporting MAEs from Dose 
1 (Day 1) up to study end (Day 209). 
• 
Percentage of participants reporting SAEs from Dose 
1 (Day 1) up to study end (Day 209). 
• 
Percentage of participants reporting newly diagnosed 
pIMDs from Dose 1 (Day 1) up to study end (Day 
209). 
• 
Percentage of participants reporting pre-existing 
pIMDs from Dose 1 (Day 1) up to study end (Day 
209). 
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Objectives 
Endpoints and estimands 
AE: adverse event; CD4+/CD8+ : cluster of differentiation 4/8; CD40L: cluster of differentiation 40 ligand; CFC: cell 
flow cytometry; ELISA: enzyme-linked immunosorbent assay; 
 GMC: geometric 
mean concentration; 
 HSVTI: HSV-targeted 
immunotherapy; IFN- : interferon-gamma; IL (IL-2, IL-13, IL-17) : interleukin; MAE: medically attended event; pIMD: 
potential immune-mediated disease; SAE: serious adverse event; TNF-: tumour necrosis factor-alpha. 
Details related to attributes of estimand covering intercurrent events, population and 
treatment definition are provided in the Section 9. 
4. 
STUDY DESIGN 
4.1. 
Overall design 
This is a Phase 1, randomized, placebo-controlled, observer-blind, single-country study 
with 3 parallel groups (refer to Figure 1): 
• 
HSVTI_F1group: approximately 20 HSV-2 seronegative participants aged 18 to 40 
years will receive 2 doses of HSVTI 
. 
• 
HSVTI_F2 group: approximately 20 HSV-2 seronegative participants aged 18 to 40 
years will receive 2 doses of HSVTI
. 
• 
Placebo group: approximately 10 HSV-2 seronegative participants aged 18 to 40 
years will receive 2 doses of placebo as control. 
The study will be overseen by an iSRC (refer to Section 8.2.3). 
Day 57 will be considered as the Primary Completion Date. 
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Figure 1 
Study design overview 
 
D: day; HSVTI: HSV-targeted immunotherapy iSRC: internal safety review committee; N: number of participants; PC: phone call; V: visit; PBMC: peripheral blood mononuclear cell 
# The iSRC evaluation will take place approximately once a month until all participants complete the Day 57 visit to review all accumulated safety data. Ad hoc iSRC evaluations can 
be triggered in case any safety concern is observed. 
* A first analysis will be performed on all data available and as clean as possible, when data for at least primary and secondary endpoints up to Day 57 are available 
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Table 4 
Study groups, intervention and blinding 
Study groups Number of 
participants 
Age 
(Min-Max) 
Study interventions 
Blinding 
Visit 1 → Visit 5 
(Observer-blind) 
Phone call 
(Observer-blind) 
HSVTI_F1 
group 
20 
18 - 40 years 
HSVTI 
X 
X 
HSVTI_F2 
group 
20 
18 - 40 years 
HSVTI 
X 
X 
Placebo group 
10 
18 - 40 years 
Placebo (saline) 
X 
X 
4.2. 
Scientific rationale for study design 
This study will provide reactogenicity, safety and immunogenicity data in HSV-2 
seronegative ethnic Japanese participants for 2 formulations of 
 
 
Randomization is used to reduce selection bias and the placebo group is included as a 
control for reactogenicity, safety and immunogenicity assessments since there are 
currently no other existing HSV interventions that could be used as control. The study 
will be observer-blind as the presentation of the study intervention and the placebo is 
different. 
4.3. 
Justification for dose 
The 2 HSVTI formulations used in the present study were selected based on the safety 
and immunogenicity data obtained in study TH HSV REC-003 (215336) PART I on 
HSV-2 seronegative men and women aged 18 to 40 years. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if the participant is available for 
the last scheduled contact (Day 209) as described in the protocol. 
EoS is defined as LSLV (Day 209) or Date of the last testing released of the Human 
Biological Samples, related to primary and secondary endpoints, whichever occurs later. 
EoS must be achieved no later than 8 months after LSLV. EoS cannot be before LSLV. 
5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardize the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
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• 
Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g., completion of the diary cards, return for follow-up 
visits). 
• 
Written informed consent obtained from the participant prior to performance of any 
study-specific procedure. 
• 
Healthy participants as established by medical history and physical examination, at 
the discretion of the investigator, before entering into the study. 
• 
Man or woman aged 18 to 40 years, included, at the time of screening. 
• 
Japanese ethnic origin (defined as having been born in Japan with 4 ethnic Japanese 
grandparents and able to speak Japanese). 
• 
Women of non-childbearing potential may be enrolled in the study. Refer to Section 
10.4.1 for definitions of women of childbearing potential, menarche and menopause. 
• 
Women of childbearing potential may be enrolled in the study, if the participant: 
− 
Has practiced highly effective contraception for 1 month prior to study 
intervention administration, and 
− 
Has a negative pregnancy test result at the Screening visit and on the day of each 
study intervention administration, and 
− 
Has agreed to continue highly effective contraception until Day 118, 
approximately 3 months post-Dose 2. 
Refer to Section 10.4.1.1 for definitions of woman of childbearing potential and 
Section 10.4.2 for highly effective contraception. 
Blood sample for simultaneous FSH and estradiol levels may be collected and tested 
locally at the discretion of the investigator to confirm non-reproductive potential 
according to local laboratory reference range. 
• 
Seronegative for HSV-2 as determined by Western blot performed at the Screening 
visit. 
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 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, endocrine, 
or renal functional abnormality, as determined by physical examination or laboratory 
screening tests. 
− 
Clinically significant abnormalities may include but are not limited to: evidence 
of cardiac damage, heart failure categorized as class II or greater according to 
the New York Heart Association functional classification, heart valve disease, 
pulmonary uncontrolled persistent asthma despite treatment, uncontrolled 

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diabetes, or disease or disorder that may put the participant at risk or influence 
study results. 
− 
Participants with a controlled underlying chronic co-morbidity may be enrolled, 
provided there have been no changes to their medication within 3 months prior 
to the Screening visit. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study or that would 
interfere with the immunogenicity assessments planned in this study. 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study intervention. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition or 
documented or suspected HIV infection, based on medical history and physical 
examination (no laboratory testing required). 
• 
Hypersensitivity to latex. 
• 
Recurrent history of or uncontrolled neurological disorders or seizures. 
• 
At the screening visit: hematological parameters (hemoglobin level, white blood cell, 
platelet) and/or biochemical parameters (ALT, AST, creatinine, blood urea nitrogen) 
outside the normal laboratory ranges, unless the laboratory abnormalities are 
considered not clinically significant by the investigator. 
• 
Body mass index ≤18 kg/m2 or ≥35 kg/m2. 
• 
History of any form of ocular HSV infection, HSV-related erythema multiforme, or 
HSV-related neurological complications (including meningitis, encephalitis, 
radiculopathy, myelitis). 
5.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or invasive 
medical device) other than the study intervention during the period beginning as of 
the Screening visit, or their planned use during the study period. 
• 
Planned administration or administration of a vaccine* in the period starting 15 
days* before each dose and ending 15 days* after each dose of study intervention 
administration**. 
* In case of adjuvanted and live-attenuated vaccines, this time window is to be 
increased to 30 days before and after each dose. 
** In case emergency mass vaccination for an unforeseen public health threat (e.g., a 
pandemic) is recommended and/or organized by public health authorities outside the 
routine immunization program, the time period described above can be reduced if, 
necessary for that vaccine, provided it is used according to the local governmental 
recommendations and that the Sponsor is notified accordingly. 
• 
Administration or planned administration of long-acting immune-modifying drugs at 
any time during the study period (e.g., infliximab). 

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• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study intervention or 
planned administration during the study period. 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 3 
months prior to the first study intervention dose. For corticosteroids, this will mean 
prednisone equivalent ≥20 mg/day for adult participants. Inhaled, intra-articular and 
topical steroids are allowed. 
• 
Prior receipt of a vaccine containing HSV antigens. 
5.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational intervention (drug or invasive medical device). 
5.2.4. 
Other exclusions 
• 
Pregnant or lactating woman. 
• 
Woman planning to become pregnant or planning to discontinue contraceptive 
precautions before Day 118 (approximately 3 months post-Dose 2). 
5.3. 
Lifestyle considerations 
Not applicable. 
5.4. 
Screening failures 
A screening failure is an individual who consents to participate in this study but is not 
randomized to a study intervention. Limited data for screening failures (at least informed 
consent date, demographic data, eligibility criteria check, reason for screening failure, 
and SAEs related to study participation or to a concurrent GSK medication/vaccine) will 
be collected and reported in the eCRF. 
5.5. 
Criteria for temporarily delaying enrolment/study 
intervention administration 
Study intervention administration (at Visit 1 [Day 1] and Visit 3 [Day 29]) may be 
postponed within the permitted time interval (see Table 2) until transient conditions cited 
below are resolved: 
• 
Participants with hematological/biochemical values out of normal range* which are 
expected to be temporary may be enrolled/may receive the study intervention at a 
later date within the allowed time interval. 
*Unless the laboratory abnormalities are considered not clinically significant by the 
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• 
Acute disease and/or fever. Refer to the Table 1 (schedule of activities) for definition 
of fever and preferred location for measuring temperature in this study.  
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or dosed at the discretion of the 
investigator.  
• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 
If the study intervention cannot be administered because of the special circumstance(s) 
(e.g., temporary hold of the study intervention administration as described in Section 
8.2.3) and cannot not be resolved within the permitted time interval (see Section 1.3), the 
time interval between Dose 1 and Dose 2 can be extended up to 90 days. 
Regarding participants with symptoms suggestive of Coronavirus disease 2019 (COVID-
19) or with a confirmed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) 
infection (as per WHO case definition [WHO, 2022]), and for whom a SARS-CoV-2 
polymerase chain reaction test has not been confirmed as negative, the return of the 
participant to the site will follow the specific guidance from local public health and other 
competent authorities. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to the Glossary of terms for the definition of study intervention. 
 

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6.1. 
Study interventions administered  
Table 5 
Study interventions administered 
Study intervention name: 
HSVTI_F1 
HSVTI_F2 
Placebo (saline) 
Study intervention formulation: 
NaCl (0.9%); Water for injections  
Dose form (presentation): 
Powder for suspension for 
injection (vial) 
Suspension for suspension for 
injection (vial) 
Powder for 
suspension for 
injection (vial) 
Suspension for 
suspension for 
injection (vial) 
Solution for injection (syringe) 
Type: 
Investigational 
Control 
Product category: 
Biologic 
Combination Product 
Route of administration: 
Intramuscular 
Administration site: 
• Location 
Deltoid 
• Directionality 
Not applicable 
• Laterality** 
Non-dominant arm 
Number of doses to be 
administered: 
2 
2 
2 
Volume to be administered*** 
Whole content 
Whole content 
At least 0.5 mL# 
Packaging and labeling: 
Refer to the Study Procedures Manual for further details 
Manufacturer: 
GSK 
GSK 
GSK 
  
* The HSVTI formulations used in the present study were selected based on the safety and immunogenicity data obtained in study TH HSV REC-003 (215336) PART I on HSV-2 
seronegative men and women aged 18 to 40 years. 
** The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the study intervention in the non-dominant arm, an injection in the dominant arm may 
be performed. 
*** Refer to the Study Procedures Manual for the volume after dilution. 
# The volume of the saline pre-filled syringe may be between 0.6 and 0.8 mL. The full volume is to be injected. 
 
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Study participants must be observed closely for at least 60 minutes after the 
administration of the study intervention. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope. 
All participants will be instructed to contact the study staff immediately should they 
manifest any signs or symptoms they perceive as severe or serious. 
6.2. 
Preparation, handling, storage, and accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s).  
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the SPM for more details on storage and handling of the study interventions. 
6.3. 
Measures to minimize bias: randomization and blinding  
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the individuals who 
have consented to participate in the study. The study center will be allocated a range of 
participant identification numbers. 
6.3.2. 
Randomization to study intervention 
The randomization of supplies within blocks will be performed at GSK, using MATerial 
EXcellence (MATEX), a program developed for use in SAS (Cary, North Carolina, US) 
by GSK. Entire blocks will be shipped to the study sites/warehouse. 
6.3.3. 
Intervention allocation to the participant 
Participants will be allocated individually numbered doses of the study intervention. 
Approximately 50 participants are targeted to be enrolled (20 in HSVTI_F1 group, 20 in 
HSVTI_F2 group and 10 in Placebo group). 
The randomization algorithm will use a minimization procedure accounting for HSV-1 
status (positive vs. negative) and sex (women vs. men). All minimization factors will 
have equal weighting. 
Allocation of the participant to a study group at the investigator site will be performed 
using a randomization system on internet. Refer to the SPM for additional information 
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After obtaining the signed and dated ICF from the participant and having checked and 
confirmed their eligibility, the study staff in charge of the study intervention 
administration will access the randomization system on internet.  
Once a participant is confirmed as a screen success, the randomization system will 
determine the study group and will provide the study intervention number to be used for 
the first dose. The study intervention number(s) to be used for subsequent dosing will be 
provided by the same automated randomization system on internet. 
The number of each study intervention administered must be recorded in the eCRF on the 
study intervention administration screen. 
When randomization system on internet is not available, please refer to the randomization 
system on internet user guide or SPM for specific instructions. 
6.3.4. 
Blinding and unblinding 
Data will be collected in an observer-blind manner. The participant, the site and sponsor 
personnel involved in the clinical evaluation of the participants are blinded, while other 
study personnel may be aware of the treatment assignment. To do so, study interventions 
will be prepared and administered by qualified study personnel who will not participate 
in data collection, evaluation, review or the entry of any study endpoint (i.e., safety). 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention groups and the identity of the participant. 
6.3.4.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
In case of emergency, the investigator can have unrestricted, immediate and direct access 
to the participant’s study intervention information via a randomization system on internet. 
The investigator may contact a GSK Helpdesk (refer to Table 6) if help is needed to 
access participant’s study intervention information (i.e., if the investigator is unable to 
access SBIR). 
A physician other than the investigator (e.g., an emergency room physician) or 
participant or family member may also request emergency access to the participant’s 
study intervention information either via the investigator (preferred option) or 
investigator’s back-up or via the GSK Helpdesk (back-up option). The participant card 
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Table 6 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Japan: 00 531 320 109 
Back-up: 00 800 4344 1111 
Fax: +32 2 401 25 75 
Email: rix.ugrdehelpdesk@gsk.com 
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs 
GSK Global Safety staff may unblind the intervention assignment for any participant 
with a SUSAR. GSK Global Safety is responsible for unblinding the study intervention 
assignment within the timeframes defined for expedited reporting of SAEs (refer to 
Section 10.3.11.1). For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. GSK policy 
requires unblinding of any unexpected SAE which is attributable/suspected to be 
attributable to the study interventions, prior to regulatory reporting. 
6.4. 
Study intervention compliance 
When the study intervention is administered at the study site, participants will receive it 
directly from the unblinded study staff, under medical supervision. The date of 
administration of each study intervention dose will be recorded in the source documents. 
6.5. 
Dose modification 
Not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
Not applicable. 
6.7. 
Treatment of overdose 
Not applicable. 
6.8. 
Concomitant therapy 
At each study visit/contact, the investigator(s) or their delegate(s) should question the 
participant about all medications/products taken, and vaccinations received by the 
participant. 

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The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medications, including vaccines/products, administered until Day 
57. 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (refer to Sections 5.2.2 
and 9.2.1 for further details). 
• 
All concomitant medication which may explain/cause/be used to treat an 
SAE/pIMDs including vaccines/products, as defined in Sections 8.3.1 and 10.3.9. 
These must also be recorded in the Expedited Adverse Event report. 
• 
All concomitant medications associated with MAEs, including vaccines/products, 
administered after the first dose of study intervention (Day 1) until study end (Day 
209). 
The LML should be contacted if there are any questions regarding concomitant or prior 
therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of the study intervention. A participant who discontinued the study 
intervention may continue other study procedures (e.g., safety or immunogenicity), 
planned in the study protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
AE requiring expedited reporting to GSK 
• 
Unsolicited non-serious AE  
• 
Solicited AE 
• 
Not willing to receive study intervention 
• 
Other (specify). 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose.  

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Participants who meet any of the criteria listed below should not receive additional doses 
of study intervention. Such participants should be encouraged to continue other study 
procedures, at the investigator’s discretion (Section 10.3.9.2). All relevant criteria for 
discontinuation of study intervention administration must be recorded in the eCRF.  
• 
Participants who experience any SAE judged to be related to study intervention or 
non-study concomitant vaccine/product. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participants if they continue to 
participate in the study. 
• 
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 his/her clinical 
judgment prior to administering the next dose of study intervention. Refer to Section 
10.3.6.1 for the definition of pIMDs. 
• 
Abnormal hematological and biochemical parameters, unless the laboratory 
abnormalities are considered temporary or not clinically significant by the 
investigator. 
• 
Occurrence of an AE assessed as related to the study intervention following the 
previous dose administration, which may place the participant at unreasonable or 
significant risk of injury or illness following repeat exposure to study intervention, 
based on the investigator’s judgment. 
• 
Anaphylaxis or other hypersensitivity reactions following the administration of study 
intervention. 
• 
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• 
Pregnant or lactating. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for them since the date of 
withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who was not 
available for the concluding contact planned in the protocol. 
Investigators 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: 

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• 
AEs requiring expedited reporting to GSK (refer to Section 10.3.11.1 for details)  
• 
Unsolicited non-serious AEs 
• 
Solicited AE 
• 
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 the participant has withdrawn 
consent and the reason for withdrawal was provided, the investigator must document this 
reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.9.2). 
7.3. 
Lost to follow-up 
Participants will be considered ‘lost to follow-up’ if they fail to return for scheduled visits 
and cannot be contacted by the study site. 
Please refer to the SPM for a description of actions to be taken before considering the 
participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with the sponsor 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 schedule of activities (Section 
1.3).  
All screening evaluations must be completed and the results reviewed before confirming 
that potential participants meet all eligibility criteria.  
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 

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Procedures conducted as part of routine clinical management (e.g. hematologic profiles), 
and obtained before the participant signed the ICF, may be used for screening and/or for 
establishing a clinical baseline (provided the procedure met protocol specified criteria 
and was performed within the time frame defined in the schedule of activities [Section 
1.3]). 
The SPM provides the investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
In exceptional situations (e.g., pandemic), consider following points: 
• 
Safety follow-up can be performed by phone calls as a way of communicating with 
the participant to monitor the participant’s progress. 
• 
Diary cards can be sent by conventional mail. 
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.  
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 the participant’s 
consent. These additional requirements must be formally communicated to, discussed and 
agreed with GSK. 

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8.1.1. 
Biological samples 
Table 7 
Biological samples 
Sample Type 
Quantity 
Unit 
Timepoint 
Sub-cohort Name 
Blood sample HSV testing 
Approximately 3.5 
mL 
Screening* 
All screened participants 
Blood sample for hematology 
analysis 
Approximately 2.0 
mL 
Screening* 
All screened participants 
Days 1, 8, 29, 36 
and 57 
All participants 
Blood sample for biochemical 
analysis 
Approximately 3.5 
mL 
Screening* 
All screened participants 
Days 1, 8, 29, 36 
and 57 
All participants 
Blood sample for antibody 
determination (humoral 
immunogenicity) analysis 
Approximately 8.5 
mL 
Days 1, 29 and 57 
All participants 
Blood sample (PBMC) for CMI 
response analysis 
Approximately 30.0 
mL 
Days 1, 29 and 57 
All participants 
Approximately 17.0 
mL 
Days 1, 29 and 57 
All participants 
Approximately 10.0 
mL 
Days 1 and 57 
All participants 
Approximately 30.0 
mL 
Days 1, 29 and 57 
All participants who will 
consent for it 
 HSV: herpes simplex virus; 
 
 CMI: cell-mediated immunity; PBMC: peripheral blood mononuclear cell 
*If deemed necessary by the investigator, re-testing can be performed within the allowed interval. 
An overall blood volume of  313 mL will be collected during the entire study period 
from all participants. 
8.1.2. 
Laboratory assays 
Table 8 
Laboratory assays  
Assay Type 
System 
Component 
Method 
Laboratory 
Screening 
Serum 
Anti-HSV antibodies 
Western Blot 
University of Washington 
Molecular Virology laboratory 
Humoral immunity 
(antibody determination) 
Serum 
antibodies 
ELISA 
GSK* or in a laboratory 
designated by GSK 
Cell-mediated immunity 
PBMC 
 
(CD4+/CD8+) T-cells 
CFC 
ELISA: enzyme-linked immunosorbent assay; 
 HSV: herpes simplex virus; 
PBMC: peripheral blood mononuclear cell; CD4+/CD8+: cluster of differentiation 4/8; CFC: cell flow cytometry 
* GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. 
Please 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. 
CCI
CCI
CCI
CCI
CCI
CCI

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Note that tertiary objectives and endpoints/estimands are optional and might be assessed 
only if needed; therefore, not all related testings might be performed and reported. 
Additional exploratory testing on the disease under study may be performed within the 
framework of the study if deemed necessary for accurate interpretation of the data or 
should such assay(s) become available at GSK’s laboratory or a laboratory designated by 
GSK. These assay(s) may not be represented in the objectives/endpoints/estimands of the 
Protocol and may be described in ancillary study Protocol(s), as needed. 
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. 
8.1.3. 
Immunological read-outs 
Table 9 
Immunological read-outs 
Blood Sampling Timepoint 
Sub-cohort Name 
Number of 
Participants 
Component 
Type of Contact and Timepoint 
Screening 
All screened 
participants 
> 50 
Anti-HSV antibodies 
Humoral Immunity 
Visit 1 (Day 1) 
Visit 3 (Day 29) 
Visit 5 (Day 57) 
All participants 
~ 50 
 antibodies 
Cell-mediated Immunity 
Visit 1 (Day 1) 
Visit 3 (Day 29) 
Visit 5 (Day 57) 
All participants 
~ 50 
 
(CD4+/CD8+) T-cells 
; HSV: herpes simplex virus; CD4+/CD8+: cluster of differentiation 4/8 
CCI
CCI
CCI
CCI
CCI

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8.1.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the HSVTI. 
8.2. 
Safety assessments 
The investigator(s) and their designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant’s withdrawal from the study 
intervention and/or study. 
8.2.1. 
Pre-intervention administration procedures 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as year of birth, sex at birth, HSV-1 status, race, and 
ethnicity in the participant’s eCRF during the Screening visit. 
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the trial participants, and to determine if the trial participants are truly representative of 
the impacted population.  
8.2.1.2. 
Measure and record height and weight 
Height and weight will be collected during the Screening visit in order to calculate the 
participant’s body mass index (as part of the eligibility criteria). Data will be recorded in 
the eCRF. 
8.2.1.3. 
Medical and vaccination history 
Obtain the participant’s medical and vaccination history by interviewing the participant 
and/or review of the participant’s medical records. Record any pre-existing conditions, 
signs and/or symptoms present prior to the Screening visit in the eCRF. 
*The following vaccination history must be checked and recorded, if applicable: 
• 
Any previous administration of an investigational HSV vaccine at any time. 
• 
Any vaccines to be administered between the Screening visit and Visit 1 (Day 1). 
8.2.1.4. 
Perform physical examination 
• 
A physical examination will be performed for each participant at the Screening visit 
and before each study intervention administration (Visit 1 [Day 1] and Visit 3 
[Day 29]). The following information will be recorded in the eCRF: oral body 
temperature, resting vital signs (before blood collection for laboratory test), 

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including systolic/diastolic blood pressure, and heart rate after at least 10 minutes of 
rest. 
• 
A targeted physical examination at each subsequent visit will be performed only if 
the participant indicates during questioning that he/she might have some underlying 
pathology(ies) or if deemed necessary by the investigator or delegate. Collected data 
do not need to be recorded in the eCRF, unless required (see Section 8.3). 
• 
If the investigator determines that the participant’s health on the day of study 
intervention administration (Visit 1 [Day 1] and Visit 3 [Day 29]) temporarily 
precludes dosing, the visit will be rescheduled within the allowed interval (see Table 
2). Refer to Section 5.5 for the list of criteria for temporary delay of study 
intervention administration. 
• 
Treatment of any abnormality observed during this examination must be performed 
according to local medical practice outside this study or by referral to an appropriate 
healthcare provider. 
8.2.1.5. 
Perform pregnancy test 
Women of childbearing potential must perform a urine pregnancy test 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.  
• 
Only women with negative pregnancy test result at the Screening visit will be 
included in the study. 
• 
The study intervention may only be administered if the pregnancy test result is 
negative at Visit 1 (Day 1) and Visit 3 (Day 29). 
For women of non-childbearing potential, the specific reason for not performing a 
pregnancy test (pre-menarche, bilateral tubal ligation or occlusion, hysterectomy, 
bilateral ovariectomy, post-menopause or other) needs to be documented in the 
participant’s source document. 
Refer to Section 10.4.3.1 for the information on study continuation for participants who 
become pregnant during the study. 
8.2.2. 
Clinical safety laboratory tests 
Refer to Section 10.2.2 for the list of clinical laboratory safety assessments required by 
the protocol. These assessments must be conducted according to the clinical laboratory 
manual and the schedule of activities (Section 1.3). The analyses of these samples will be 
performed locally. 
8.2.3. 
Study holding rules and safety monitoring 
This study will be overseen by an iSRC operating under a charter and by a SRT (in a 
blinded manner). The iSRC is a group of GSK experts (clinicians, safety representatives 
and statisticians), independent from the HSV-targeted immunotherapy project team, with 

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a proper medical and scientific expertise to guarantee the safety and wellbeing of the 
participants. 
The iSRC evaluation will take place approximately once a month until all participants 
complete Day 57 visit to review all accumulated safety data. In addition to the planned 
iSRC evaluations, ad hoc iSRC evaluations can be triggered if any potential safety issue 
is observed. 
During an iSRC evaluation, the iSRC will determine whether any of the predefined 
holding rules (refer to Table 10) are met or whether there is any other safety signal, based 
on all available unblinded safety data.  
8.2.3.1. 
Study Holding Rules 
Holding rules to be applied during the Study Intervention Administration Phase are 
presented in Table 10. Meeting any of these holding rules will trigger a hold of study 
intervention irrespective of number of participants enrolled and/or timing of the event. 
• 
Holding rules 1a-1d will be monitored by the investigators on a continuous basis 
throughout the study. Meeting any of these holding rules will trigger a hold of study 
intervention administration, irrespective of number of participants enrolled and/or 
timing of the event. 
If an investigator detects one of the holding rules mentioned above, the study 
intervention administration will be immediately put on hold. GSK will be 
immediately informed and the data will be entered in the eCRF. It is GSK’s 
responsibility to put the study intervention administration on hold at all sites. 
• 
Holding rules will be assessed by the iSRC during safety evaluations on unblinded 
data. Meeting any of these holding rules will trigger a hold of study intervention 
administration. 
Of note, no formal holding rules will be applied for other safety data such as 
non-life-threatening SAEs (those that are not meeting the definition of holding rule 1b), 
missed visits due to study intervention related AEs, Grade 1 and Grade 2 solicited and 
unsolicited AEs in the 7-day follow-up period and unsolicited AEs collected from 7 to 28 
days after study intervention administration (refer to Section 10.3.10.1 for assessment of 
intensity). However, to the extent of their availability, these data will also be reviewed by 
the SRT and iSRC to allow an overall assessment of the benefit/risk ratio of study 
intervention administration. 

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Table 10 
Study Holding Rules 
Holding 
Rule 
Event 
Number of 
Participants 
1a 
Death or any life-threatening SAE, regardless of causality 
≥ 1 
1b 
Any non-life-threatening SAE that can be reasonably attributed to the study intervention 
administration 
≥ 1 
1c 
Any withdrawal from the study (by investigator’s or participant’s request) and/or study 
intervention administration, following a Grade 3 AE 
≥ 1 
1d 
Any solicited administration site or solicited systemic AE leading to hospitalization, or 
necrosis at the injection site, with an event onset within the 7-day (Days 1-7) post-study 
intervention administration period 
≥ 1 
2a 
Any Grade 3 solicited administration site AE (lasting 48 hours or more) in an 
investigational group, with an event onset within the 7-day (Days 1-7) post-study 
intervention administration period 
≥ 25% (and ≥ 2 
participants in 
each HSVTI 
group) 
2b 
Any Grade 3 solicited systemic AE (lasting 48 hours or more) in an investigational 
group, with an event onset within the 7-day (Days 1-7) post-study intervention 
administration period 
≥ 25% (and ≥ 2 
participants in 
each HSVTI 
group) 
2c 
Any Grade 3 unsolicited AE in an investigational group, that can be reasonably 
attributed to the study intervention administration, with an event onset within the 28-days 
(Days 1-28) post-study intervention administration period 
OR 
Any Grade 3 abnormality* in pre-specified hematological or biochemical laboratory 
parameters in an investigational group, between Day 1 and Day 29 post-study 
intervention administration period 
≥ 25% (and ≥ 2 
participants in 
each HSVTI 
group) 
AE: adverse event; SAE: serious adverse event 
*Grading of laboratory parameters will be based on the FDA Guidance for Industry “Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” (see Table 18). 
Figure 2 illustrates the probability to reach the study holding rules following study 
intervention administration: 
• 
For holding rules 1, using a cut-off of 1/20, there is more than 80% chance that the 
holding rule is met for a study intervention with a true incidence rate above 8% and 
there is more than 36% chance that the holding rule is not met for a study 
intervention with a true incidence rate below 5%. 
• 
For holding rules 2, using a cut-off of 5/20, there is more than 80% chance that the 
holding rule is met for a study intervention with a true incidence rate above 32% and 
there is more than 63% chance that the holding rule is not met for a study 
intervention with a true incidence rate below 20%. 

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Figure 2 
Risk Assessment Curves for Study Holding Rules 
 
If a holding rule is met, the investigator must suspend administration of the study 
intervention and inform GSK immediately (e.g. holding rules 1a-d). Refer to Table 13 for 
contact information. GSK will inform the investigator if holding rules 2a-c are met.  
The following communication sequence must be followed:  
• 
The concerned study staff must put study interventions administration on hold. 
• 
The concerned study staff must immediately inform their local GSK contact defined 
in Section 8.3.3.1). 
• 
LML will inform the CSL, who will then inform the iSRC chair and the SRT lead.  
• 
All informed study staff will confirm to their local contact that action has been taken 
to provide appropriate documentation to GSK. 
• 
GSK will further evaluate the case by the iSRC and GSK’s GSB and will take the 
decision to restart the study intervention administration, modify or stop the study. All 
study staff will be informed about that final decision by their local GSK contact. 
In case the study is put on hold while a participant is in the screening process, and the 
timing to conduct the first study intervention administration at Visit 1 (Day 1) would 
exceed the interval defined in Table 2, all screening procedures as detailed in the SoA 
(Table 1) must be performed again. Data from this re-screening, if performed, must be 
encoded in the eCRF.  
8.2.3.2. 
Outcome of Safety Evaluation 
• 
If no safety concern is observed, the favorable outcome of safety evaluations will be 
documented and provided in a written way to the investigators. 

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• 
If a safety concern is observed during the safety evaluations or if any of the holding 
rules is met (Table 10): 
− 
The study CSL (or his/her delegate) will be accountable for notifying the 
investigator to temporarily put all study intervention administration on hold 
immediately, but all other procedures relating to safety and immunogenicity can 
continue as planned for participants received at least one dose of study 
intervention. 
− 
Following an internal review, GSK will decide to suspend, modify or continue 
the conduct of the study. This decision will be communicated to the investigator/ 
IEC/IRB and PMDA as applicable by national regulation.  
Refer to Section 10.1.5 for details regarding the iSRC and SRT. 
 

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8.3. 
Adverse Events, Serious Adverse Events and other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other safety information  
Table 11 
Timeframes for collecting and reporting of safety information 
 
Screening* 
 
Visit 1 
 
Visit 2 
 
Visit 3 
 
Visit 4 
Visit 5 
Phone call 
Event 
Up to 56 days 
before Visit 1 
 
Day 1 
Day 7 
Day 8 
Day 28 
Day 29 
Day 35 
Day 36 
Day 57 
Day 209 
 
Dose 1 
7 days 
post-
Dose 1 
 
28 days 
post-Dose 
1 
Dose 2 
7 days 
post-
Dose 2 
 
28 days 
post-Dose 2 
Study 
conclusion 
Administration site and systemic 
solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MAEs 
pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs (all, fatal, related) 
AEs/SAEs leading to withdrawal 
from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies and outcome 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE: adverse event; MAE: medically attended event; pIMD: potential immune-mediated disease; SAE: serious adverse event 
*i.e., consent obtained 
 

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The investigator or designee will record and immediately report all SAEs in enrolled 
participants to the sponsor or designee 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 Section 10.3.11. The investigator will submit any 
updated SAE data to the sponsor within 24 hours of it being available.  
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 11. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
if the investigator considers the event to be reasonably related to the study intervention, 
the investigator will promptly notify the study contact for reporting SAEs mentioned in 
the Table 13. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events  
Detection and recording of AE/SAE/pIMD/pregnancies are detailed in Section 10.3.9.  
Assessment of AE/SAE intensity, causality and outcome are described in Section 
10.3.10.  
Open-ended and non-leading verbal questioning of participants is the preferred method of 
acquiring information related to an AE/SAE/pIMD/pregnancy.  
8.3.2.1. 
Clinically significant abnormal laboratory findings 
The investigator must review the laboratory report, document that the review occurred, 
and record any clinically relevant changes occurring during the study in the AE section of 
the eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
• 
All clinically significant abnormal laboratory test values reported during the study or 
within 28 days after the last dose of study intervention should be repeated until the 
values return to normal/baseline, or until they are no longer considered significantly 
abnormal by the investigator. Refer to Section 10.3.7 for more information on 
clinically abnormal laboratory assessments that qualify as an AE or SAE. 
• 
If such values do not return to normal/baseline after an interval judged reasonable by 
the investigator, the etiology of the abnormal value should be identified, and the 
sponsor notified. 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies and 
other events  
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/pIMD/pregnancy, it must be reported to GSK using the required 

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documentation and within the timeframes mentioned in Table 12. This is essential for 
GSK to meet 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 Section 10.3.10.2. 
Local regulatory requirements and sponsor policy for preparation of an investigator 
safety report of SUSAR must be followed. These reports will be forwarded to 
investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities/regulatory agencies 
about the safety of an investigational study intervention. The sponsor will comply with 
country-specific regulatory requirements related to safety reporting to the regulatory 
authority, IRB/IEC and investigators. 
Please refer to Section 10.3.11 for further details regarding the reporting of 
SAEs/pIMDs/pregnancies. 
Table 12 
Timeframes for submitting SAE, pregnancy and other events reports 
to GSK  
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies  
24 hours* 
electronic pregnancy 
report  
24 hours* 
electronic pregnancy report  
pIMDs 
24 hours** 
‡‡  
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡‡ For each SAE/pIMD, the investigator(s) must document in the medical notes that they have reviewed the 
SAE/pIMD and have provided an assessment of causality. 

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8.3.3.1. 
Contact information for reporting SAEs, pIMDs, pregnancies and study 
holding rules 
Table 13 
Contact information for reporting SAEs, AESIs, pregnancies and 
study holding rules 
Study contact for questions regarding 
SAEs, pIMDs, pregnancies  
Study contact for reporting of study 
holding rules  
Refer to the local study contact information 
document 
If a holding rule is met, the investigator must 
immediately inform the LML. 
Back-up study contact for reporting SAEs, 
pIMDs, pregnancies 
Available 24/24 hours and 7/7 days: 
Back-up study contact for escalation of 
holding rules 
Refer to the local study contact information 
document 
GSK Global Safety 
 
Email address: ogm28723@gsk.com 
 
8.3.4. 
Treatment of expedited adverse events (SAE/pIMD) 
Any medication administered for the treatment of an SAE/pIMD should be recorded in 
the Expedited Adverse Event Report of the participant’s eCRF screen (refer to Section 
10.3.11.1). 
8.3.5. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician/family member 
that the participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator(s) or their back-up. 
8.3.6. 
Safety follow-up call 
At 6 months post-Dose 2 telephone contacts, participants will be queried in accordance 
with a template script provided separately by GSK. Participants will be queried about 
concomitant medications, any intercurrent medical conditions, and the occurrence of 
pIMDs, SAEs, concurrent vaccination, SAEs related to study participation or to a 
concurrent GSK medication/vaccine, and AEs or SAEs leading to withdrawal. 
Information collected will be documented in the source document and will be recorded in 
the eCRF. 
8.4. 
Pharmacokinetics 
Not applicable. 

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8.5. 
Genetics 
In this study, genetics may be evaluated after review by the ethical review committee in 
accordance with the Japanese Ethical Guidelines for Medical and Biological Research 
Involving Human Subjects. 
A 30 mL blood sample (PBMC) for DNA isolation will be collected at Visits 1, 3 and 5 
(Days 1, 29 and 57) from participants who have consented to participate in the genetic 
research of the study. 
Participants who do not wish to participate in the genetic research may still participate in 
the study. 
See Section 10.5 for information regarding genetic research.  
8.6. 
Biomarkers 
Not applicable. 
8.7. 
Immunogenicity assessments 
Immunogenicity is described in Section 8.1. 
8.8. 
Health outcomes 
Not applicable. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
No formal statistical hypotheses are to be tested. All analyses will be descriptive. 

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9.2. 
Analysis sets 
Table 14 
Analysis sets 
Analysis set 
Description 
Screened set 
All participants who were screened for eligibility 
Enrolled set  
All participants who entered the study (who were randomized or received study 
intervention or underwent a post-screening procedure) 
Exposed Set (ES) 
All participants who will receive at least 1 dose of the study intervention. 
Per Protocol for 
immunogenicity set 
(PPS_Immuno) 
All eligible participants who will receive all doses as per protocol, will have 
immunogenicity results post-dose, will comply with dosing/blood draw intervals, 
without intercurrent conditions that may interfere with immunogenicity and without 
prohibited concomitant medication/vaccination. The analysis will be done 
according to the study intervention that participants received at dose 1. 
Per Protocol for CMI set 
(PPS_CMI) 
All eligible participants who will receive all doses as per protocol, will have CMI 
results post-dose, will comply with dosing/blood draw intervals, without intercurrent 
conditions that may interfere with immunogenicity and without prohibited 
concomitant medication/vaccination. The analysis will be done according to the 
study intervention that participants received at dose 1. 
9.3. 
Statistical analyses 
The SAP will include a more technical and detailed description of the statistical analyses. 
This section is a summary of the planned statistical analyses. 
The analyses will be descriptive with the aim to characterize the safety/reactogenicity, 
and immunogenicity in each group. 
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Any deviation(s) or change(s) from the original statistical plan outlined in this Protocol 
will be described and justified in the final CSR. 
9.3.1. 
Participants Disposition 
The number of enrolled and administered (at least one dose, full dose course) 
participants, included in each group and in total, will be described. 
9.3.2. 
Demography and Baseline Characteristics Analyses 
Demographic characteristics (age at first study intervention administration in years, sex at 
birth, HSV-1 status, race, and ethnicity) will be summarized overall and by study 
intervention group using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables. 
• 
Mean, SD, median, minimum and maximum will be provided for continuous data 
such as age, height, weight, and body mass index. 
Withdrawal status will be summarized by group using descriptive statistics: 
• 
The numbers of withdrawn participants will be tabulated according to the reason for 
withdrawal. 
• 
The number of participants enrolled into the study as well as the number of 
participants excluded from the PPS will be tabulated. 

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9.3.3. 
Primary Endpoints/Estimands Analyses 
The analysis of the primary reactogenicity and safety objective will be performed on the 
ES. 
Statistical Analysis Methods 
The percentage of participants reporting at least one solicited AE, at least one solicited administration site AE, and 
at least one solicited systemic AE during the 7-day follow-up period (i.e., Day 1-Day 7 post-each study intervention 
administration) will be tabulated for each group after each dose and overall. 
The percentage of participants reporting each individual solicited administration site AE (any grade and Grade 3) 
and solicited systemic AE (any grade and Grade 3) during the 7-day follow-up period (i.e., Day 1-Day 7 post-each 
study intervention administration) will be tabulated for each group after each dose and overall. 
For solicited AEs, percentages will be computed based on the total number of solicited symptoms screens completed.
For each group and for each hematology and biochemistry parameter: 
• 
The percentage of participants having hematology and biochemistry results below or above the laboratory 
normal ranges will be tabulated by timepoint. 
• 
The summary of grading post-study intervention administration will be tabulated vs. baseline. Grades will be 
based on the FDA Guidance for Industry “Toxicity Grading Scale for Healthy Adults and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials”; see Section 10.2.2). The laboratory parameters not included on 
FDA Toxicity Grading Scale will not be graded. 
The percentage of participants with any unsolicited AEs during the 28-day follow-up period (i.e., Day 1-Day 28 
post-each study intervention administration) with its exact 95% CI will be tabulated by group and by MedDRA PTs. 
Similar tabulation will be done for Grade 3 unsolicited AEs, for any causally related unsolicited AEs, for Grade 3 
causally related unsolicited AEs and for unsolicited AEs resulting in a medically attended visit. The verbatim reports 
of unsolicited AEs will be reviewed by a qualified person and the signs and symptoms will be coded according to the 
MedDRA Dictionary for Adverse Reaction Terminology. Every verbatim term will be matched with the appropriate PT. 
For unsolicited AEs, percentages will be computed based on the total number of exposed participants. Participants 
not reporting an AE will be considered as not having experienced any AE. 
The percentage of participants with any AEs (solicited and unsolicited) resulting in a medically attended visit from 
Dose 1 up to 28 days post last dose administered (Day 57, or Day 29 if only one dose administered) will also be 
tabulated by MedDRA SOC and PT by group, after each dose and overall with exact 95% CI. 
The percentage of participants with at least one report of SAE, with at least one report of causally related SAE, with 
at least one report of fatal SAE, and with at least one report of causally related fatal SAE classified by the MedDRA 
SOC and PTs reported from Dose 1 up to 28 days post last dose administered (Day 57, or Day 29 if only one dose 
administered) will be tabulated by group with exact 95% CI. 
The percentage of participants with at least one newly diagnosed pIMD and at least one exacerbation of a pre-
existing pIMD classified by the MedDRA SOC and PTs and reported from Dose 1 up to 28 days post last dose 
administered (Day 57, or Day 29 if only one dose administered) will be tabulated by group with exact 95% CI. 
The percentage of participants using concomitant medication (any medication, any antipyretic, and any antipyretic 
taken prophylactically, respectively) during the 7-day follow-up period (i.e., Day 1-Day 7 post-each study 
intervention administration) and during the 28-day follow-up period (i.e., Day 1-Day 28 post-each study intervention 
administration) will be summarized by group after each dose and overall. 

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9.3.4. 
Secondary Endpoints/Estimands Analyses 
The analysis of the secondary humoral immunogenicity objectives will be performed on 
the PPS for analysis of immunogenicity (PPS_immuno). The analysis of the secondary 
CMI objectives will be performed on the PPS for analysis of CMI (PPS_CMI). If more 
than 10% of participants are eliminated from any of the PPS in any treatment group, a 
sensitivity analysis will be carried out using the ES. The analysis of the secondary safety 
objective will be performed on the ES. 
Statistical Analysis Methods 
The percentage of participants with any AEs (solicited and unsolicited) resulting in a medically attended visit from 
Dose 1 up to study end (Day 209) will also be tabulated by MedDRA SOC and PT by group, after each dose and 
overall with exact 95% CI. 
The percentage of participants with at least one report of SAE, with at least one report of causally related SAE, with 
at least one report of fatal SAE, and with at least one report of causally related fatal SAE classified by the MedDRA 
SOC and PTs reported from Dose 1 up to study end (Day 209) will be tabulated by group with exact 95% CI. 
The percentage of participants with at least one newly diagnosed pIMD and at least one exacerbation of a pre-
existing pIMD classified by the MedDRA SOC and PTs and reported from Dose 1 up to study end (Day 209) will be 
tabulated by group with exact 95% CI. 
For each group, at each timepoint that blood samples are collected for immune responses and for each assay 
(unless otherwise specified): 
• 
Seropositivity rates and their 95% CI will be tabulated. 
• 
GMCs/GMTs and their 95% CI will be tabulated and represented graphically. 
 
 
• 
Mean geometric fold increases and their 95% CI will be tabulated and represented graphically. 
 
 
• 
Percentage of participants that had a study intervention response defined as a 4-fold increase in concentration 
and their CI will be tabulated by group. 
 
.  
• 
Antibody titer/concentration will be displayed using reverse cumulative curves. 
• 
The kinetics of titers will be plotted as a function of time for participants. 
• 
The frequency of specific CD4+/CD8+ T-cells will be summarised (mean, SD, minimum, Q1, median, Q3, and 
maximum) by group, at each timepoint during which blood samples are collected for CMI (descriptive statistics). 
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9.3.5. 
Tertiary Endpoints/Estimands Analyses 
Tertiary endpoint analyses will be described in the statistical analysis plan. 
9.4. 
Sequence of analyses 
• 
A primary analysis will be performed on all data available and when data for at 
least primary and secondary endpoints up to Day 57 are available. 
At this point, the statistician will be unblinded (i.e., will have access to the individual 
participant treatment assignment). The remaining study personnel will stay blinded 
(i.e., will not have access to the individual participant treatment assignment). It is 
possible however, due to the limited sample size, that unblinding occurs for a few 
participants having a specific AE or SAE (e.g., an AE/SAE occurring only in a single 
participant). Therefore, anyone having access to this analysis could become 
unblinded regarding those specific cases. This would be acceptable given the 
early/descriptive nature of the study and the limited number of expected unblinding. 
Investigators and participants will remain blinded up to study end (Day 209). The 
investigators will not be provided with the individual data listings or with the 
randomization listings until the end of study analysis. 
• 
The end of study analysis will be performed when all data for primary and 
secondary endpoints up to study conclusion are available (Day 209). Individual 
listings will only be provided at this stage. 
• 
If data for tertiary endpoints become available at a later stage, (an) additional 
analysis/analyses will be performed. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
The names and addresses of all third parties involved in this study are provided in a 
separate document accompanying this study protocol. 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations  
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines 
− 
Applicable ICH 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 for review and 
approval. These documents will be signed and dated by the investigator before the 
study is initiated.  
• 
Any protocol amendments will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
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− 
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/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
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 
study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator(s) or their representative(s) must fully explain the nature of the study to 
the participant and answer all questions regarding the study.  
Participants must be informed that their participation is voluntary.  
Freely given and written informed consent must be obtained from each participant prior 
to participation in the study.  
The content of the ICF must meet the requirements of 21 CFR 50, local regulations, ICH 
guidelines, HIPAA requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF.  
Participants must be re-consented if a new version of the ICF(s) or an ICF addendum is 
released during their participation in the study.   
A copy of the ICF(s) must be provided to the participants. 
Participants who are rescreened are required to sign a new ICF, only if there are changes 
to the original ICF. If there are no changes to the original ICF, participants should 
confirm that they still agree to be part of the study. This information should be captured 
in the participant source document. 
In case of unexpected pregnancy, participant must be informed that personal information 
such as date of birth or sex of the baby will be collected as part of safety follow-up. 

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Consent for the baby may be obtained from the participants and/or their partner as per 
local regulations. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets transferred to the sponsor 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 participants must be informed that: 
• 
Their personal study-related data will be used by the sponsor in accordance with 
local data protection law.  
• 
Their medical records may be examined by Clinical Quality Assurance auditors or 
other authorized personnel appointed by the sponsor, by appropriate IRB/IEC 
members, and by inspectors from regulatory authorities. 
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. 
10.1.5. 
Committees structure 
This Protocol will be reviewed and approved by an IEC/IRB before initiation (refer to 
Section 10.1.1 for further details). 
Safety oversight will be carried out by an iSRC that will be set-up for the safety 
monitoring throughout the study intervention administration phase and by an existing 
project SRT (refer to Section 8.2.3 for further details): 
• 
The iSRC is a group of GSK experts (including physicians), external to the ongoing 
study/project and with lack of conflicts of interest in the outcome of the study, who 
assess the reactogenicity and safety data in an unblinded (on a participant-level or 
study intervention administration group-level) fashion. Based on its review, the iSRC 
gives recommendations to the primary contact (study CSL) regarding study 
modification, continuation or termination. Should any issues or potential safety 
concerns be identified, the iSRC Chair escalates issues to the GSB Co-Chairs (Chief 
Medical Officer and Head of Global Safety). 
• 
The SRT of the HSVTI project includes as core members GSK’s Central Safety 
product specialists (including a physician), the CPL, Epidemiologist, Global 
Regulatory Lead, Global Medical Affairs Lead, and Biostatistician of the project, as 
well as study CSL and study Statistician as ad hoc members. The SRT is responsible 
for ongoing safety monitoring of the entire project and meets on a regular basis. The 
SRT will inform the iSRC and GSB about any potential safety concern relevant to 
the study (should there be any identified in a blinded manner). 

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10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical study registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided access to statistical tables, 
figures, and relevant reports. GSK will also provide the investigator with the full 
summary of the study results. The investigator is encouraged to share the summary 
results with the study participants, as appropriate. 
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis. 
GSK intends to make anonymized patient-level data from this study available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (refer to the Glossary of terms for the definitions 
of essential and source documents). The document storage system used during the study 
and for archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential study documents may be added or removed where justified (in advance of study 
initiation) based on their importance and relevance to the study. When a copy is used to 
replace an original document (e.g. source documents, eCRF), the copy should fulfill the 
requirements for certified copies (refer to the Glossary of terms for the definition of 
certified copy).  
All participant data related to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The investigator must maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the site’s study participants 
(refer to the Glossary of terms for the definition of source documents) that supports 
information entered in the eCRF.  

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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.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data (refer to the Glossary of terms for the definition of 
source data).  
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
QTLs will be predefined in the Quality Plan 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 CSR. 
Study records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 
10.1.9. 
Study and site start and closure 
First act of recruitment 
The start of study is defined as FSFV at a country level. 

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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 will: 
• 
Review collected data to ensure accuracy and completeness. 
• 
Complete Screening Conclusion for screen failures in the eCRF. 
• 
Complete the Study Conclusion screen in the eCRF. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor 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. 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the LSLV for interventional studies and 
follows the guidance from the ICMJE. 

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10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Laboratory Assays Description 
Descriptions of available assays are provided below. Descriptions could be subject to 
change, due to assay(s) being under development.  
HSV serology by Western blot 
 proteins from detergent lysates of HSV infected cells are separated by 
electrophoresis then transferred to nitrocellulose paper. The strips of paper or ‘blots’ 
containing either separated, fixed proteins from 
 are then incubated with 
the participant’s serum. Antibodies, which bind to the viral proteins, are then detected by 
an enzyme-mediated color change. The pattern of staining on the 2 blots (
 
) is dictated by the number and identity of the HSV proteins to which the 
participant’s immune system has responded. Thus, a predominance of staining on either 
the 
 antigen-containing blot allows serotyping of the sera. In 80% of 
cases, this is all that is required. If the serotype is uncertain, the serum is adsorbed against 
both 
 proteins, and re-run on fresh blots to obtain clearer profiles 
(essentially removing type common antibody) [Ashley, 1988]. 
 testing by ELISA 
The 
 IgG ELISA is under development and the procedure could change. The 
assay will be based on an indirect solid phase ELISA allowing the detection and 
quantification of total IgG antibodies directed against the 
 heterodimer in human 
serum samples. 
The principle of this assay will be as follows: the mutated heterodimer
 antigen will 
be adsorbed onto a 96-well polystyrene microplate. After a washing and a blocking step, 
dilutions of serum samples, controls and standard(s) will be added to the coated 
microplate. After incubation, the microplate will be washed to remove unbound primary 
antibodies. Bound IgG will be detected by the addition of a secondary anti-IgG human 
antibody conjugated to HRP. Bound antibodies will be quantified by the addition of the 
HRP substrate solution, whereby a colored product develops proportionally to the amount 
of 
 IgG antibodies present in the serum sample. The corresponding antibody 
concentration, corrected for the dilution factor, will be expressed in EU/mL, units 
arbitrarily chosen as no existing reference standard is available. 
Intracellular cytokine staining 
Intracellular cytokine staining has been used to assess CMI responses as previously 
described [Díez-Domingo, 2010; Moris, 2011]. 
Briefly, thawed PBMC are stimulated in vitro with either 
 
) or with culture medium only in the presence of anti-CD28 and 
anti-CD49d antibodies. After 2 hours of incubation at 37°C, Brefeldin A is added to 
inhibit cytokine secretion during an additional overnight incubation. Cells are 
subsequently harvested, stained for surface markers (CD4+ and CD8+) and then fixed. 
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Fixed cells are then permeabilised and stained with fluorescently labelled antibodies 
specific for the following immune markers: 
• 
CD3: phenotyping T-cells, 
• 
CD40L (CD154), 4-1BB: expressed on activated CD4 (or CD8) T-cells 
[Chattopadhyay, 2005; Frentsch, 2005; Samten, 2000; Stubbe, 2006], 
• 
Interleukin (IL)-2: key for the development, survival and function of T-cells 
[Boyman, 2012], 
• 
Tumour necrosis factor-alpha (TNF-): antiviral/intracellular factor, pro-
inflammatory cytokine, cytotoxicity [Sedger, 2014], 
• 
Interferon-gamma (IFN-): antiviral factor, associated with the Th1 profile (and 
CD8) T-cells [Schoenborn, 2007], 
• 
IL-13: associated with the Th2 profile [Bao, 2015], 
• 
IL-17: associated with the Th17 profile [Korn, 2009]. 
 
. 
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10.2.2. 
Protocol required safety laboratory assessments 
The tests detailed in Table 17 will be performed by a laboratory designated by the 
sponsor.  
Table 17 
Hematology and Biochemistry Read-Outs 
Sampling Timepoint 
Sub-cohort Name 
Number of 
Participants 
Component 
Type of Contact and Timepoint 
Screening 
All screened participants 
≥ 50 
Hemoglobin 
WBC differential 
Platelets 
ALT 
AST 
Creatinine 
Blood urea nitrogen 
Visit 1 (Day 1) 
Visit 2 (Day 8) 
Visit 3 (Day 29) 
Visit 4 (Day 36) 
Visit 5 (Day 57) 
All participants 
50 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; WBC: white blood cells 
Table 18 
Toxicity Grading Scales for Hematology and Biochemistry 
Parameters Applicable for this Study 
Component 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life-Threatening 
(Grade 4) 
Hematology (Whole Blood) 
Hemoglobin (g/dL) - female 
11.0 - 12.0 
9.5 - 10.9 
8.0 - 9.4 
< 8.0 
Hemoglobin (g/dL) - male 
12.5 - 13.5 
10.5 - 12.4 
8.5 - 10.4 
< 8.5 
Hemoglobin (g/dL) - female 
change from baseline value 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (g/dL) - male 
change from baseline value 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC increase (cell/mm3) 
10 800 - 15 000 
15 001 - 20 000 
20 001 - 25 000 
> 25 000 
WBC decrease (cell/mm3) 
2 500 - 3 500 
1 500 - 2 499 
1 000 - 1 499 
< 1 000 
Platelets decrease (cell/mm3) 
125 000 - 140 000 
100 000 - 124 000 
25 000 - 99 000 
< 25 000 
Biochemistry (Serum) 
ALT (increase by factor) 
1.1 - 2.5 х ULN 
2.6 - 5.0 х ULN 
5.1 - 10 х ULN 
> 10.0 х ULN 
AST (increase by factor) 
1.1 - 2.5 х ULN 
2.6 - 5.0 х ULN 
5.1 - 10 х ULN 
> 10.0 х ULN 
Creatinine (mg/dL) 
1.5 - 1.7 
1.8 - 2.0 
2.1 - 2.5 
> 2.5 or requires 
dialysis 
Blood urea nitrogen (mg/gL) 
23 - 26 
27 – 31 
> 31 
Requires dialysis 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of the normal range; WBC: white 
blood cells 
The laboratory values provided in the table are taken from the FDA Guidance for Industry “Toxicity Grading Scale for 
Healthy Adults and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” dated September 2007. 
These laboratory values serve as guidelines and are dependent upon institutional normal parameters. Institutional 
normal reference ranges should be provided to demonstrate that they are appropriate. 

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10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting  
10.3.1. 
Definition of an adverse event (AE)  
An AE is any untoward medical occurrence (an unfavorable/unintended sign - including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.3.1.1. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the 
condition/indication under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g. hospital stays, physician 
visits and emergency room visits). 
• 
Pre- or post-intervention events that occur as a result of protocol-mandated 
procedures (i.e. invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
Clinically significant abnormal laboratory findings or other abnormal 
assessments that are present at baseline and significantly worsen following 
the start of the study will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited AEs are described in the Section 10.3.3. All 
other AEs will be recorded as UNSOLICITED AEs. 
10.3.1.2. 
Events NOT Meeting the AE Definition 
• 
Situations where an untoward medical occurrence did not occur (e.g. social 
and/or convenience admission to a hospital, admission for routine 
examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.  

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• 
Pre-existing conditions or signs and/or symptoms present in a participant 
before the first dose of study intervention. These events will be recorded in 
the medical history section of the eCRF.  
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from 
baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal 
safety assessments associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s 
condition. 
10.3.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. Results in death 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an 
event in which the participant was at risk of death at the time of the event. It 
does not refer to an event, which hypothetically might have caused death, had 
it been more severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been 
admitted (usually involving at least an overnight stay) at the hospital or 
emergency ward for observation and/or treatment that would not have been 
appropriate in the physician’s office or outpatient setting. Complications that 
occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When 
in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
d. Results in disability/incapacity  
Note: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza like illness, and accidental 
trauma (e.g. sprained ankle) which may interfere or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant.  
f. 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy). 
g. Other situations 

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Medical or scientific judgment must be exercised in deciding whether 
reporting is appropriate in other situations. Important medical events that 
may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the participant or require medical or surgical 
intervention to prevent one of the other outcomes listed in the above 
definition should be considered serious. Examples of such events are invasive 
or malignant cancers; intensive treatment in an emergency room or at home 
for allergic bronchospasm; blood dyscrasias; and convulsions that do not 
result in hospitalization. 
10.3.3. 
Solicited events 
a. Solicited administration site events 
The following administration site events will be solicited: 
Table 19 
Solicited administration site events 
Pain at administration site 
Redness at administration site 
Swelling at administration site 
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 20 
Solicited systemic events 
Fever 
Headache 
Myalgia (muscle pain) 
Arthralgia (joint pain) 
Fatigue (tiredness) 
Note: Participants will be instructed to measure and record the oral temperature in the 
evening. If additional temperature measurements are taken at other times of the day, 
participants will be instructed to record the highest temperature in the diary card. 
10.3.4. 
Unsolicited AEs 
An unsolicited AEs is an adverse event that was either not included in the list of solicited 
events or could be included in the list of solicited events but with an onset outside the 
specified period of follow-up for solicited events. Unsolicited AEs must have been 
communicated by a participant who has signed the informed consent. Unsolicited AEs 
include both serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e. symptoms or illnesses requiring 
a hospitalization, or an emergency room visit, or visit to/by a health care provider). The 
participants will be instructed to contact the site as soon as possible to report medically 
attended event(s), as well as any events that, though not medically attended, are of 
participant’s concern. Detailed information about reported unsolicited AEs will be 
collected by qualified site personnel and documented in the participant’s records. 

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Unsolicited AEs that are not medically attended or perceived as a concern by the 
participant will be collected during an interview with the participants and by review of 
available medical records at the next visit. 
10.3.5. 
SAEs related to Study Participation 
Any SAEs related to study participation (e.g. SAEs due to study mandated procedures, 
invasive tests or change in existing therapy) should be reported as per Section 8.3.3. 
10.3.6. 
Adverse events of special interest 
10.3.6.1. 
Potential immune-mediated diseases 
pIMDs are 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 21 (refer to Section 10.3.9.1 for reporting details). 
The investigator(s) must exercise their 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 study intervention administration) or as an exacerbation of a pre-
existing chronic condition (if it exacerbated following study intervention administration) 
in the eCRF. 
Table 21 
List of potential immune-mediated diseases (pIMDs) 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and cold antibody hemolytic 
anemia 
Autoimmune lymphoproliferative 
syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Autoimmune thrombocytopenia 
• 
Frequently used related terms include: “autoimmune thrombocytopenic 
purpura”, “idiopathic thrombocytopenic purpura (ITP)”, “idiopathic 
immune thrombocytopenia”, “primary immune thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with 
thrombocytopenia syndrome 
(TTS) 
 
Thrombotic thrombocytopenic 
purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic hemolytic 
anemia” 

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Medical Concept 
Additional Notes 
Cardio-pulmonary inflammatory disorders 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms include 
“Interstitial lung disease”, “Pulmonary fibrosis”, “Immune-mediated 
pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis 
(PAP) 
• 
Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-mediated 
thyroiditis  
Including but not limited to: 
• 
Hashimoto thyroiditis (autoimmune hypothyroidism, lymphocytic 
thyroiditis) 
• 
Atrophic thyroiditis  
• 
Silent thyroiditis  
• 
Thyrotoxicosis 
Autoimmune diseases of the 
testis and ovary 
• 
Includes autoimmune oophoritis, autoimmune ovarian failure and 
autoimmune orchitis 
Autoimmune hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 
Grave's or Basedow’s disease 
• 
Includes Marine Lenhart syndrome and Graves' ophthalmopathy, also 
known as thyroid eye disease (TED) or endocrine ophthalmopathy 
Insulin autoimmune syndrome 
 
Polyglandular autoimmune 
syndrome 
• 
Includes Polyglandular autoimmune syndrome type I, II and III 
Eye disorders 
Ocular Autoimmune / Immune-
mediated disorders 
Including but not limited to: 
• 
Acute macular neuroretinopathy (also known as acute macular outer 
retinopathy) 
• 
Autoimmune / Immune-mediated retinopathy  
• 
Autoimmune / Immune-mediated uveitis, including idiopathic uveitis and 
sympathetic ophthalmia  
• 
Cogan's syndrome: an oculo-audiovestibular disease 
• 
Ocular pemphigoid 
• 
Ulcerative keratitis 
• 
Vogt-Koyanagi-Harada disease 

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Medical Concept 
Additional Notes 
Gastrointestinal disorders 
Autoimmune / Immune-mediated 
pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel disease  
Including but not limited to:  
• 
Crohn’s disease  
• 
Microscopic colitis  
• 
Terminal ileitis 
• 
Ulcerative colitis  
• 
Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• 
Dermatomyositis 
• 
Inclusion body myositis 
• 
Immune-mediated necrotizing myopathy 
• 
Polymyositis 
Mixed connective tissue disorder 
 
Polymyalgia rheumatica (PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• 
Rheumatoid arthritis associated conditions 
• 
Juvenile idiopathic arthritis 
• 
Palindromic rheumatism 
• 
Still's disease 
• 
Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• 
Ankylosing spondylitis 
• 
Juvenile spondyloarthritis 
• 
Keratoderma blenorrhagica 
• 
Psoriatic spondylitis  
• 
Reactive Arthritis (Reiter's Syndrome) 
• 
Undifferentiated spondyloarthritis 
Systemic Lupus Erythematosus  
• 
Includes Lupus associated conditions (e.g. Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) or complications such as 
shrinking lung syndrome (SLS) 

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Medical Concept 
Additional Notes 
Systemic Scleroderma (Systemic 
Sclerosis) 
• 
Includes Reynolds syndrome (RS), systemic sclerosis with diffuse 
scleroderma and systemic sclerosis with limited scleroderma (also 
known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis (ADEM) and 
other inflammatory-
demyelinating variants  
Includes the following: 
• 
Acute necrotizing myelitis 
• 
Bickerstaff's brainstem encephalitis  
• 
Disseminated necrotizing leukoencephalopathy (also known as 
Weston-Hurst syndrome, acute hemorrhagic leuko-encephalitis, or 
acute necrotizing hemorrhagic encephalomyelitis)  
• 
Myelin oligodendrocyte glycoprotein antibody-associated disease 
• 
Neuromyelitis optica (also known as Devic’s disease) 
• 
Noninfective encephalitis / encephalomyelitis / myelitis 
• 
Postimmunization encephalomyelitis  
Guillain-Barré syndrome (GBS) 
• 
Includes variants such as Miller Fisher syndrome and the acute motor 
and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (e.g. Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous cataplexy 
Peripheral inflammatory 
demyelinating neuropathies and 
plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner Syndrome 
or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), 
including atypical CIDP variants (e.g. multifocal acquired demyelinating 
sensory and motor neuropathy also known as Lewis-Sumner 
syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute complete 
transverse myelitis (ACTM) 

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Medical Concept 
Additional Notes 
Renal disorders 
Autoimmune / Immune-mediated 
glomerulonephritis  
Including but not limited to: 
• 
IgA nephropathy 
• 
IgM nephropathy 
• 
C1q nephropathy 
• 
Fibrillary glomerulonephritis 
• 
Glomerulonephritis rapidly progressive 
• 
Membranoproliferative glomerulonephritis 
• 
Membranous glomerulonephritis 
• 
Mesangioproliferative glomerulonephritis 
• 
Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-mediated 
blistering dermatoses  
Including but not limited to:  
• 
Bullous Dermatitis 
• 
Bullous Pemphigoid  
• 
Dermatitis herpetiformis  
• 
Epidermolysis bullosa acquisita (EBA)  
• 
Linear IgA-mediated bullous dermatosis (LABD), also known as Linear 
IgA disease 
• 
Pemphigus  
Erythema multiforme 
 
Erythema nodosum 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• 
Interstitial granulomatous dermatitis 
• 
Palisaded neutrophilic granulomatous dermatitis 
Lichen planus 
• 
Includes liquen planopilaris 
Localized Scleroderma 
(Morphoea) 
• 
Includes Eosinophilic fasciitis (also called Shulman syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson Syndrome 
(SJS) 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small 
vessels vasculitis  
Including but not limited to: 

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Medical Concept 
Additional Notes 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis (type 
unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  
• 
Erythema induratum (also known as nodular vasculitis) 
• 
Henoch-Schonlein purpura (also known as IgA vasculitis) 
• 
Microscopic polyangiitis 
• 
Necrotizing vasculitis 
• 
Polyarteritis nodosa 
• 
Single organ cutaneous vasculitis, including leukocytoclastic vasculitis, 
hypersensitivity vasculitis and acute hemorrhagic edema of infancy 
(AHEI) 
• 
Wegener's granulomatosis  
Other (including multisystemic) 
Anti-synthetase syndrome 
 
Capillary leak syndrome 
• 
Frequently used related terms include : “systemic capillary leak 
syndrome (SCLS)” or “Clarkson's Syndrome” 
Goodpasture syndrome 
• 
Frequently used related terms include : “pulmonary renal syndrome” 
and “anti-Glomerular Basement Membrane disease (anti-GBM 
disease)” 
Immune-mediated enhancement 
of disease 
• 
Includes vaccine associated enhanced disease (VAED and VAERD). 
Frequently used related terms include “vaccine-mediated enhanced 
disease (VMED)”, “enhanced respiratory disease (ERD)”, “vaccine-
induced enhancement of infection”, “disease enhancement”, “immune 
enhancement”, and “antibody-dependent enhancement (ADE) 
Immunoglobulin G4 related 
disease 
 
Langerhans' cell histiocytosis 
 
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 
 
When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as pIMD. Symptoms, signs or conditions which might (or might not) lead to one 
of the above diagnoses, should be recorded and reported as AEs but not as pIMD until the 
final or definitive diagnosis has been made, and alternative diagnoses eliminated or 
shown to be less likely.  

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10.3.7. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings assessments or other 
abnormal results the investigator considers clinically significant will be recorded as an 
AE or SAE, if they meet the definition of an AE or SAE (refer to Sections 10.3.1 and 
10.3.2).  
The investigator(s) must exercise their medical and scientific judgment in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.8. 
Events or outcomes not qualifying as AEs or SAEs  
10.3.8.1. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy 
outcome or complication or elective termination of a pregnancy for medical reasons will 
be recorded and reported as an SAE. Please refer to Section 10.3.2 for definition of SAE.  
10.3.9. 
Recording and follow-up of AEs, SAEs, pIMDs and pregnancies  
The participants will be instructed to contact the investigator immediately should they 
experience any signs or symptoms they perceive as serious.  
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) related to 
the event. The investigator will then record all relevant information regarding an AE/SAE 
on the eCRF. The investigator may not send photocopies of the participant’s medical 
records to GSK instead of appropriately completing the eCRF.  
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on copies of the medical 
records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event, based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE instead of individual signs/symptoms. 
A Paper Diary (pDiary) will be used in this study to capture solicited and unsolicited 
administration site or systemic events. The participant should be trained on how and 
when to complete the pDiary. At each study intervention administration visit, pDiary will 
be provided to the participant. The participant will be instructed to measure and record 
the oral body temperature and any solicited administration site or systemic events or any 

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unsolicited AEs occurring after study intervention administration. The participant will be 
instructed to return the completed diary card to the Investigator at the next study visit.  
Anyone who measures administration site or systemic events and who will record the 
event in the pDiary should be trained on using the pDiary. This training must be 
documented in the participant’s source record. 
If any individual other than the participant is making entries in the pDiary, their identity 
must be documented in the participant’s source record. 
Any unreturned pDiary will be sought from the participant through telephone call(s) or 
any other convenient procedure. 
The investigator or delegate will transcribe the required information into the eCRF in 
English.  
10.3.9.1. 
Time period for collecting and recording AEs, SAEs, pIMDs and 
pregnancies  
All AEs that occur during 7 days following administration of each dose of study 
intervention (Day 1 to Day 7) must be recorded into the appropriate section of the eCRF, 
irrespective of their intensity or whether or not they are considered related to the study 
intervention.  
All unsolicited AEs that occur during 28 days following administration of each dose of 
study intervention (i.e., on the day of study intervention administration and 27 subsequent 
days) must be recorded into the appropriate section of the eCRF, irrespective of their 
intensity or whether or not they are considered related to the study intervention. 
The time period for collecting and recording SAEs (all, fatal and related) will begin at the 
first receipt of study intervention (Day 1) and will end at study end (Day 209). See 
Section 10.3.11 for instructions on reporting of SAEs. However, any SAEs assessed as 
related to study participation (e.g., Protocol-mandated procedures, invasive tests or 
change in existing therapy) or related to a GSK product will be recorded from the time a 
participant consents to take part in the study (i.e., at the Screening visit). 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study intervention (Day 1) until study end (Day 209). 
The time period for collecting and recording MAEs will begin at the first receipt of study 
intervention (Day 1) and will end at study end (Day 209). 
The time period for collecting and recording pIMDs will begin at the first receipt of study 
intervention (Day 1) and will end at study end (Day 209). See Section 10.3.11 for 
instructions on reporting of pIMDs. 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study intervention (Day 1) and will end at study end (Day 209). See Section 10.3.11 for 
instructions on reporting of pregnancies. 

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10.3.9.2. 
Follow-up of AEs, SAEs, pIMDs, pregnancies or any other events of 
interest  
After the initial AE/SAE/pIMD/pregnancy or any other event of interest, the investigator 
is required to proactively follow each participant at subsequent visits/contacts. All SAEs 
and pIMDs (as defined in the Section 10.3.6), will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up. 
Other non-serious AEs must be followed until event is resolved, stabilized, otherwise 
explained, or until the participant is lost to follow-up. 
10.3.9.2.1. Follow-up during the study 
All AEs documented at a previous visit/contact and defined as not recovered/not resolved 
or recovering/resolving will be reviewed at subsequent visits/contacts until 28 days after 
the last study intervention administration. 
All SAEs and (serious or non-serious) pIMDs documented at a previous visit/contact and 
defined as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contacts until the last study visit of the participant. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.9.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE/pIMD using an electronic Expedited Adverse Events Report 
and/or pregnancy report as applicable. The investigator is obliged to perform or arrange 
for the conduct of supplemental clinical examinations/tests and/or evaluations to 
elucidate the nature and/or causality of the SAE/pIMD as fully as possible. 
10.3.9.2.3. Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At the 
end of the pregnancy, whether full-term or premature, information on the status of the 
mother and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period does not 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
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 GSK as described in the Section 10.3.11. 

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10.3.9.3. 
Updating of SAE, pIMD and pregnancy information after removal of 
write access to the participant’s eCRF 
When additional SAE, pIMD or pregnancy information is received after write access to 
the participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study contact for reporting SAEs (refer to Section 
8.3.3.1 or to GSK Global Safety department within the defined reporting timeframes 
specified in the Table 12). 
10.3.10. 
Assessment of intensity and causality 
10.3.10.1. Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 22 
Intensity scales for solicited events  
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes 
with everyday activities. 
 
3 
Severe: Significant pain at rest. Prevents normal 
everyday activities. 
Redness at administration site 
0 
< 25 mm 
1 
25 - 50 mm 
2 
51 - 100 mm 
3 
> 100 mm 
Swelling at administration site 
0 
< 25 mm 
1 
25 - 50 mm 
2 
51 - 100 mm 
3 
> 100 mm 
Temperature* 
0 
< 38.0°C (< 100.4°F) 
1 
38.0°C (100.4°F) - 38.4°C (101.1°F) 
2 
38.5°C (101.2°F) - 38.9°C (102.0°F) 
3 
> 38.9°C (> 102.0°F) 
Headache 
0 
None 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal 
activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue (tiredness) 
0 
None 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Myalgia (muscle pain) 
0 
None 
 
1 
Mild: Myalgia present but does not interfere with 
activity 
 
2 
Moderate: Myalgia that interferes with normal activity 
 
3 
Severe: Myalgia that prevents normal activity 

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Event 
Intensity grade 
Parameter 
Arthralgia (joint pain) 
0 
None 
 
1 
Mild: Arthralgia present but does not interfere with 
activity 
 
2 
Moderate: Arthralgia that interferes with normal 
activity 
 
3 
Severe: Arthralgia that prevents normal activity 
* Refer to the Table 1 (schedule of activities) for the definition of fever and the preferred location for temperature 
measurement. 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The intensity 
should be assigned to one of the following categories (see Table 23). Where applicable, 
the assessment will be based on the investigator’s clinical judgment. 
Table 23 
Intensity Scales for Unsolicited AEs 
Event 
Grade 1 (mild) 
Grade 2 (moderate) 
Grade 3 (severe) 
Tachycardia (beats per minute) 
101 – 115 
116 – 130 
> 130 
Bradycardia (beats per minute) 
50 – 54 
45 – 49 
< 45 
Hypertension (systolic) (mm Hg) 
141 – 150 
151 – 155 
> 155 
Hypertension (diastolic) (mm Hg) 
91 – 95 
96 – 100 
> 100 
Hypotension (systolic) (mm Hg) 
85 – 89 
80 – 84 
< 80 
Respiratory rate (breaths per minute) 
17 – 20 
21 – 25 
> 25 
Nausea/vomiting 
No interference with 
activity or 1 – 2 
episode(s)/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily activity, 
requires outpatient 
intravenous hydration 
Diarrhoea 
2 – 3 loose stools or 
< 400 g/24 hours 
4 – 5 stools or 400 - 
800 g/24 hours 
6 watery stools or 
> 800 g/24 hours or 
requires outpatient 
intravenous hydration 
Illness or clinical adverse event 
No interference with 
activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily 
activity and requires 
medical intervention 
The values/definitions provided in the table are taken from the FDA Guidance for Industry “Toxicity Grading 
Scale for Healthy Adults and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” dated 
September 2007. 
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. 
10.3.10.2. Assessment of causality 
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgment. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 

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Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB while making their assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
: 
There is a reasonable possibility that the study intervention 
contributed to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to 
the administration of the study intervention. There are other, 
more likely causes and administration of the study intervention is 
not suspected to have contributed to the AE. 
If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedures not required by the protocol. 
• 
An error in study intervention administration. 
• 
Other causes (specify).  
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited 
Adverse Events Report to GSK.  
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The investigator(s) may change their opinion of causality after 
receiving additional information and update the SAE information accordingly. 
10.3.10.3. Medically attended visits 
For each solicited and unsolicited AE the participant experiences, the participant will be 
asked if they received medical attention (defined as unscheduled visit to or from medical 
personnel for any reason, including emergency room visits). This information will be 
recorded in the participant’s diary. Medical attention received for SAEs/pIMDs will have 
to be reported using the normal AE reporting process in the eCRF. 

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10.3.10.4. Assessment of outcomes 
The investigator will assess the outcome of all serious and non-serious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
10.3.11. 
Reporting of SAEs, pIMDs, pregnancies and other events 
10.3.11.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred in enrolled participant, the 
investigator (or designee) must complete information in the electronic Expedited Adverse 
Events Report WITHIN 24 HOURS, even if the investigator does not have complete 
information on the SAE. It must be completed as thoroughly as possible, with all 
available details of the event.  
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 12 for the details on timeframes for reporting of 
SAEs/pIMDs/pregnancies.  
Refer to Section 10.3.11.2 for information on back-up systems in case the electronic 
reporting system does not work. 
10.3.11.2. Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax 
or email a completed, dated and signed paper Expedited Adverse Events Report to the 
study contact for reporting SAEs (refer to Sponsor Information) or to GSK Global Safety 
department within 24 hours of becoming aware of the SAE.  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours after the electronic reporting system is working again. The information 
reported through the electronic SAE reporting system will be considered valid for 
regulatory reporting purposes. 

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10.4. 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of childbearing potential 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.4.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth.  
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 
Note: Documentation can come from the site personnel’s review of participant’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high FSH level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrolment. 
10.4.2. 
Contraception guidance 
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
24).  

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Table 24 
Highly effective contraceptive methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• 
Oral 
Highly Effective Methods That Are User Independent  
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the woman of childbearing potential and the absence of 
sperm has been confirmed. If not, an additional highly effective method of contraception 
should be used.)  
Male partner sterilization prior to the female participant’s entry into the study, and this male is the 
sole partner for that participant, 
(The information on the male sterility can come from the 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 drug. 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.)  
*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 in clinical studies 
10.4.3. 
Collection of pregnancy information 
10.4.3.1. 
Female participants who become pregnant 
Refer to Sections 8.3.1, 8.3.2, 10.3.9.1, 10.3.9.2 and 10.3.9.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any woman who becomes pregnant during the study must not receive additional dose(s) 
of the study intervention but may continue other study procedures at the discretion of the 
investigator. 
10.5. 
Appendix 5: Genetics 
Genetic determinants that impact immune response may result in variable immune 
response to the study intervention(s). Therefore, where local regulations and IRB/IEC 
allow, a blood sample will be collected for DNA analysis. 

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DNA samples will be used for research related to HSVTI. They may also be used to 
develop tests/assays (including diagnostic tests) related to HSVTI. 
DNA samples will be analyzed if it is hypothesized that this may help further 
understanding of the clinical data. 
10.6. 
Appendix 6: Definition of medical device AE, adverse device 
effect, serious adverse device effect and unanticipated 
SADE  
Not applicable. 
10.7. 
Appendix 7: Country-specific requirements 
10.7.1. 
Regulatory and ethical considerations 
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW Notification 
No.28 dated 27th March, 1997)” and Pharmaceuticals and Medical Devices Act. 
The statement “I agree to assume responsibility for the proper conduct of the study at this 
site.” on the Investigator Protocol Agreement Page means the investigator’s 
responsibility as defined by Japanese GCP. 
GSK Japan will submit the CTN to the regulatory authorities in accordance with 
Pharmaceuticals and Medical Devices Act before conclusion of any contract for the 
conduct of the study with study sites. 
10.7.2. 
Study administrative structure 
Administrative Information and List of Medical Institutions and Investigators are 
included in Exhibit 1 and Exhibit 2, respectively. 
10.7.3. 
Unapproved medical device 
Details, if any, will be added in Exhibit 3.  

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10.8. 
Appendix 8: Abbreviations and glossary of terms 
10.8.1. 
List of abbreviations  
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
CD4+/CD8+ 
Cluster of differentiation 4/8 
CD40L 
Cluster of differentiation 40 ligand 
CFC 
Cell flow cytometry 
CI 
Confidence Interval 
CIOMS 
Council for International Organizations of Medical 
Sciences 
CMI 
Cell-mediated immunity 
COVID-19 
Coronavirus disease 2019 
CPL 
Clinical Project Lead 
CSL 
Clinical Sciences Lead 
CSR 
Clinical Study Report 
DNA 
Deoxyribonucleic acid 
eCRF 
electronic Case Report Form 
ELISA 
Enzyme-linked immunosorbent assay 
EoS 
End of Study 
CCI
CCI

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ES 
Exposed Set 
FDA 
Food and Drug Administration, United States of 
America 
FSFV 
First subject first visit 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMC/GMT 
Geometric Mean Concentration/ Geometric Mean Titer 
GSB 
Global Safety Board 
GSK 
GlaxoSmithKline Biologicals SA 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRP 
Horseradish peroxidase  
HRT 
Hormonal replacement therapy 
HSV 
Herpes Simplex Virus 
HSVTI 
HSV-targeted immunotherapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IFN- 
Interferon-gamma 
IgA/G/M 
Immunoglobulin A/G/M 
IL (IL-2, IL-13, IL-17) 
Interleukin 
CCI
CCI
CCI

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IRB 
Institutional Review Board 
iSRC 
Internal Safety Review Committee 
LML 
Local Medical lead 
LSLV 
Last Subject Last Visit 
MAE 
Medically Attended Event 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC I/II 
Major Histocompatibility Complex I/II 
PBMC 
Peripheral blood mononuclear cell 
pIMD 
Potential immune-mediated disease 
PPS 
Per Protocol Set 
PT 
Preferred term 
QTL 
Quality Tolerance Limit 
RNA 
Ribonucleic acid 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical analysis system 
SBIR 
Source data Base for Internet Randomization  
SD 
Standard Deviation 
SOC 
System Organ Class 
SPM 
Study Procedures Manual 
SRT 
Safety Review Team 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
CCI
CCI

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TNF- 
Tumour necrosis factor-alpha 
10.8.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product.  
An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For 
marketed medicinal products, this also includes failure 
to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the study are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
study, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event.  
In an observer-blind study, the participant, the site and 
sponsor personnel involved in the clinical evaluation of 
the participants are blinded while other study personnel 
may be aware of the treatment assignment.  
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Combination product: 
Combination product comprises any combination of  
− 
drug  
− 
device  
− 
biological product  
Each drug, device and biological product included in a 
combination product is a constituent part.  
CCI

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Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolment: 
The process of registering a participant into a clinical 
study by assigning participant identification number 
after signing the ICF. 
Essential documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per protocol analysis. 
Immunological correlate of 
protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intervention: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical device 
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’. 
Investigational product: 
A pharmaceutical form of an active ingredient being 
tested in a clinical study, including a product with a 
marketing authorization when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
Synonym: Investigational Medicinal Product 
Investigator: 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team of 
individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 

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individual or party to perform those study-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). 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Pharmacogenomics 
The ICH E15 Guidance for Industry defines 
pharmacogenomics as the, “Study of variation of DNA 
and RNA characteristics as related to drug or treatment 
response.”  
Pharmacogenetics, a subset of pharmacogenomics, is 
“the study of variations in DNA sequence as related to 
drug response.” Pharmacogenomic biomarkers include 
germline (host) DNA and RNA as well as somatic 
changes (e.g. mutations) that occur in cells or tissues.  
Pharmacogenomic biomarkers are not limited to human 
samples but include samples from viruses and infectious 
agents as well as animal samples. The term 
pharmacogenomic experiment includes both the 
generation of new genetic or genomic (DNA and/or 
RNA) data with subsequent analysis as well as the 
analysis of existing genetic or genomic data to 
understand drug or treatment response 
(pharmacokinetics, safety, efficacy or effectiveness, 
mode of action).  
Proteomic and metabolomic biomarker research is not 
pharmacogenomics. 
Primary completion date: 
The date that the final participant was examined or 
received an intervention for the purpose of final 
collection of data for all primary outcomes, whether the 
clinical study was concluded according to the pre-
specified protocol or was terminated. 
Protocol amendment: 
The ICH defines a protocol amendment as: ‘A written 
description of a change(s) to or formal clarification of a 
protocol.’ GSK further details this to include a change to 
an approved protocol that affects the safety of 

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participants, scope of the investigation, study design, or 
scientific integrity of the study. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
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. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (e.g. 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical study). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Study monitor: 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Sub-cohort: 
A group of participants for whom specific study 
procedures are planned as compared to other participants 

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or a group of participants who share a common 
characteristic (e.g. ages, vaccination schedule, etc.) at 
the time of enrolment. 
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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11. 
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Signature Page for  218459 TMF-15037340 v1.0
Signature Page for TMF-15037340 v1.0
Reason for signing: Approved
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Date of signature: 20-Mar-2023 13:15:46 GMT+0000
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