A Phase I/II Observer-blind, Randomized, Multi-center Trial to Evaluate the Safety and Immunogenicity of Different Formulations of Monovalent Influenza A/Astrakhan/3212/2020 Like (H5N8) Virus Vaccine With AS03 Adjuvant System (Referred to as Q-Pan H5N8), Given as a Two-dose Series to Adults 18 to 64 Years of Age and 65 Years of Age and Older
Phase: PHASE1
Conditions: Influenza, Human
Sponsor: GlaxoSmithKline

CONFIDENTIAL 
Protocol 219833 
Amendment 3.0 
 
1 
TITLE PAGE 
Protocol Title:  
A Phase I/II observer-blind, randomized, multi-center trial to evaluate the safety and 
immunogenicity of different formulations of monovalent 
Influenza A/Astrakhan/3212/2020-like (H5N8) virus vaccine with AS03 adjuvant system 
(referred to as Q-Pan H5N8), given as a two-dose series to adults 18 to 64 years of age and 
65 years of age and older 
Protocol Number: 219833 
Abbreviated Title: FLU Q-PAN H5N8=AS03-001 
Study Phase: I/II 
Sponsor Name: GlaxoSmithKline  
Legal Registered Address:  
Rue De L’institut 89 
1330 Rixensart  
Belgium  
Date of Original Protocol: 03 May 2023 
Date of Protocol Amendment 1.0: 23 June 2023 
Date of Protocol Amendment 2.0: 22 August 2023 
Date of Protocol Amendment 3.0: 16 February 2024 

CONFIDENTIAL 
Protocol 219833 
Amendment 3.0 
 
2 
Approval Date: 16 February 2024 
Sponsor Signatory 
 
 
 
 
 
Pascal Peeters 
Sr Dir. Clinical Project Lead 
Clinical Sc. Respiratory & Global Health 
 
Date 
 
Medical Monitor name and contact information will be provided separately.  
 
 

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Protocol 219833 
Amendment 3.0 
 
3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
TABLE 
DOCUMENT HISTORY 
 
 
Document 
Date 
Substantial 
Region 
Amendment 3.0 
16 February 2024 
Yes 
Global 
Amendment 2.0 
22 August 2023 
Yes 
Global 
Amendment 1.0 
23 June 2023 
Yes 
Global 
Original Protocol 
03 May 2023 
- 
- 
Amendment 3.0: 16 February 2024 
Overall Rationale for the Amendment 3.0: 
This protocol has been amended to extend the visit windows to ensure data is included in the 
Per Protocol Set (PPS) analysis given the large number of participants whose Visit 3 or Visit 5 
was out of window. In this amendment, text from the updated GSK protocol template 
regarding publication policy has been added, and a correction to the number of times each 
serum sample will be tested in the same assay has been made in the hemagglutination 
inhibition assay section. The list of medical conditions considered to represent potential 
immune-mediated diseases (pIMDs) has been updated to the Standard MedDRA query for 
Immune-mediated/autoimmune diseases at the request of the FDA. Finally due to late 
availability of Day 43 immunogenicity data a preliminary analysis of safety data up to Day 43 
has been added.   
Added text in bold italic, deleted text in strikethrough.  
Section # and Name 
Description of Changes from 
Amendment 2.0 to Amendment 3.0 
Brief Rationale 
Section 1.3 Schedule of 
Activities, Table 2 
Interval Between Study 
Visits 
Updated allowed interval range for 
Visit 1 → Visit 3 and Visit 3 → 
Visit 5: 
• 
14 – 28 35 days 
To ensure data is included in the PPS 
analysis given the large number of 
participants whose Visit 3 or Visit 5 was 
out of window. 
Section 9.1 Statistical 
Hypotheses 
The following text was updated: 
Null hypotheses will be assessed 
independently in each of the 4 dose 
groups using a Bonferroni 
adjustment to control the 2.5% type I 
error.  
The update is done to adjust the large 
number of participants excluded from 
the PPS. 

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Protocol 219833 
Amendment 3.0 
 
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Section # and Name 
Description of Changes from 
Amendment 2.0 to Amendment 3.0 
Brief Rationale 
Null hypotheses will be assessed 
according to a hierarchical order of 
study groups as given below.  
1. 7.5 mcg antigen + AS03A 
2. 7.5 mcg antigen + AS03B 
3. 3.75 mcg antigen + AS03A 
4. 3.75 mcg antigen + AS03B 
No multiplicity adjustment is 
required as the hypothesis for each 
study group will be tested if the 
success criteria will be met for the 
previous group in the hierarchy. 
Accordingly, a nominal type I error 
of 0.6252.5% will be used for each 
dose group and the objective will be 
met for one dose group if all 2 null 
hypotheses are rejected 
simultaneously. 
Criteria for success to be met 
simultaneously for a study group: 
The lower limit (LL) of the 
98.7595% confidence interval (CI)    
for the SPR meets or exceeds 70% 
for adults of 18 to 64 years of age. 
The LL of the 98.7595% CI for the 
SPR meets or exceeds 60% for adults 
≥65 years of age. 
Section 9.2 Sample Size 
Determination 
The following text was updated: 
A non-evaluable rate of no more than 
8% yields 23% and 30% in 18 to 
64 years of age and ≥65 years of age 
groups, respectively yield an 
approximate sample size of 120 
95 evaluable participants per dose 
group (i.e., 60 50 participants 
between 18 to 64 years of age and 
60 45 participants above 65 years of 
age in each dose group), giving 
73.577.8% overall power to fulfill 
the 2 SPR immunogenicity criteria in 
any in the first group that is 7.5 mcg 
antigen + AS03Aone of the 4 dose 
groups. This assumes that the SPR 
are truly 20% higher than the critical 
value (namely 90% for participants 
18 to 64 years of age and 80% for 
The update is done to adjust the large 
number of participants excluded from 
the PPS. 

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Protocol 219833 
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Section # and Name 
Description of Changes from 
Amendment 2.0 to Amendment 3.0 
Brief Rationale 
participants ≥65 years of age, 
respectively). 
The statistical power in 7.5 mcg 
antigen + AS03A group will be 
91.4% if the SPR is assumed as 85% 
in ≥65 years of age. 
Section 9.5.1.1 Interim 
Safety Analysis 
Section 9.5.1.1 heading title was 
updated to:  
Interim Safety Analysis at Day 43. 
Due to the delay in developing the 
Hemagglutination Inhibition assay, the 
interim analysis is split into 2 separate 
deliverables of safety data and 
immunological data. 
The following text was updated: 
• 
Analyses of cleaned solicited 
administration site events and 
solicited systemic events data 
collected during a 7-day 
follow-up period (i.e., day of 
vaccination and 6 subsequent 
days) after each vaccination will 
be conducted. 
• 
Analyses of unsolicited AEs 
reported up to the Day 43 visit 
(i.e., day of vaccination and 
20 subsequent days after each 
vaccine) and cleaned in so far as 
is possible, will be carried out. 
• 
Analyses of SAEs, pIMDs, 
MAEs, pregnancies, and 
withdrawals due to AEs, 
collected up to the Day 43 visit, 
will be carried out. 
Text was updated for conciseness. 
Added text: 
• 
No study report will be 
prepared. Access to individual 
treatment codes will be 
restricted to the designated 
statisticians in charge of the 
analysis. No individual listings 
or data with the participants’ 
identifying information will be 
disseminated. Listings of final 
data will be provided with the 
EOS report. 
Clarification of the expectations for the 
interim analysis of safety. 
Removed text: 
• 
Analyses of cleaned 
immunogenicity data, for 
analysis of vaccine-homologous 
HI antibody titers and MN titers, 
Text was moved to the newly-added 
Section 9.5.1.2, Interim Immunogenicity 
Analysis at Day 43. 

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Protocol 219833 
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Section # and Name 
Description of Changes from 
Amendment 2.0 to Amendment 3.0 
Brief Rationale 
collected through the Day 43 
visit will be conducted. 
• 
Results will be presented in a 
Day 43 statistical report. Access 
to individual treatment codes 
will be restricted to the 
designated statisticians in charge 
of the analysis. No individual 
listings or data with the 
participants’ identifying 
information will be 
disseminated. Listings of final 
data will be provided with the 
EOS report. 
Section 9.5.1.2 Interim 
Immunogenicity Analysis 
at Day 43 
A new section, Interim 
Immunogenicity Analysis at Day 43, 
was added. 
This analysis will inform on the safety of 
Egg-based AS03 H5N1 vaccine that will 
be used in case a Pandemic is declared. 
The following text was added: 
An analysis will be performed on 
data collected through the Day 43 
visit. Elements will include: 
• 
Analyses of cleaned 
immunogenicity data, for 
analysis of vaccine-homologous 
HI antibody titers and MN 
titers, collected through the Day 
43 visit. 
• 
Results will be presented in a 
Day 43 statistical report. Access 
to individual treatment codes 
will be restricted to the 
designated statisticians in 
charge of the analysis. No 
individual listings or data with 
the participants’ identifying 
information will be 
disseminated. Listings of final 
data will be provided with the 
EOS report. 
Section 10.1.12 
Publication Policy 
Added text: 
Where required by regulation, the 
names of the sponsor signatory and 
investigator signatory will be made 
public. 
GSK intends to make anonymized 
participant-level data from this 
study available to external 
researchers for scientific analyses 
Newly added text to the GSK protocol 
template v3 (dated 10Jan2024). 

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Protocol 219833 
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Section # and Name 
Description of Changes from 
Amendment 2.0 to Amendment 3.0 
Brief Rationale 
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. Data will be 
shared with researchers in a 
non‑identifying way, and 
appropriate measures will be taken 
to protect PI; these measures will 
comply with data protection and 
privacy laws that apply. 
Section 10.2 Appendix 2: 
Clinical Laboratory Tests 
Updated Hemagglutination Inhibition 
Assay process: 
Briefly, serum samples are first 
adsorbed with RBCs to remove 
non-specific agglutinins and then 
treated with receptor destroying 
enzyme overnight to remove 
non-specific inhibitors of the 
hemagglutination, then diluted to 
1:10, and serial diluted 2-fold in 
triplicateduplicate from 1:10 to 
1:10240.” 
“Each seraserum sample will be 
tested in triplicateduplicate within 
the same assay. The final result 
corresponds to the GMT for the 
duplicate3 titer results will be 
reported, as will the GMT for the 
triplicate. 
Correction 
Section 10.8 Appendix 8: 
List of Potential Immune-
Mediated Diseases 
Replaced GSK list of pIMD 
MedDRA Terms version 26.0 with 
version 26.1. 
Updated list 
Section 10.9 Appendix 9 
Protocol and Amendment 
History 
Updated Appendix 9 with 
Amendment 2.0 changes. 
Version history 
Global document updates 
Version and summary of changes 
were revised. 
Version control 
 

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Protocol 219833 
Amendment 3.0 
 
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TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1 
Synopsis .......................................................................................................... 13 
1.2 
Study Design ................................................................................................... 17 
1.3 
Schedule of Activities .................................................................................... 18 
2.0 
INTRODUCTION ..................................................................................................... 21 
2.1 
Study Rationale .............................................................................................. 21 
2.2 
Background .................................................................................................... 22 
2.3 
Benefit/Risk Assessment................................................................................ 22 
3.0 
OBJECTIVES, AND ENDPOINTS ......................................................................... 24 
4.0 
STUDY DESIGN ....................................................................................................... 26 
4.1 
Overall Design ................................................................................................ 26 
4.2 
Scientific Rationale for Study Design .......................................................... 26 
4.3 
Justification for Dose ..................................................................................... 27 
4.4 
End of Study Definition ................................................................................. 27 
4.5 
Study Stopping Criteria ................................................................................ 27 
5.0 
STUDY POPULATION ............................................................................................ 28 
5.1 
Inclusion Criteria ........................................................................................... 28 
5.2 
Exclusion Criteria .......................................................................................... 28 
5.2.1 
Medical Conditions............................................................................ 28 
5.2.2 
Prior/Concomitant Therapy ............................................................... 29 
5.2.3 
Other Exclusions ................................................................................ 29 
5.3 
Screen Failures ............................................................................................... 30 
5.4 
Criteria for Temporarily Delaying Enrollment and Vaccination ............. 30 
6.0 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY ...................... 31 
6.1 
Study Interventions Administered ............................................................... 32 
6.2 
Preparation, Handling, Storage, and Accountability ................................. 34 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................... 34 
6.4 
Study Intervention Compliance ................................................................... 35 
6.5 
Dose Modification .......................................................................................... 35 
6.6 
Continued Access to Study Intervention After the End of the 
Study ............................................................................................................... 35 
6.7 
Treatment of Overdose ................................................................................. 35 
6.8 
Concomitant Therapy ................................................................................... 35 

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7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 37 
7.1 
Discontinuation of Study Intervention ........................................................ 37 
7.1.1 
Contraindications to Subsequent Study Intervention(s) 
Administration................................................................................... 37 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................... 38 
7.3 
Lost to Follow-up ........................................................................................... 39 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 40 
8.1 
Screening Procedures .................................................................................... 40 
8.1.1 
Informed Consent .............................................................................. 40 
8.1.2 
Check Inclusion and Exclusion Criteria ............................................ 40 
8.1.3 
Collection of Demographic Data ...................................................... 40 
8.1.4 
Medical History ................................................................................. 41 
8.1.5 
Physical Examinations ...................................................................... 41 
8.1.6 
Medication and Vaccination History ................................................ 41 
8.1.7 
Biological Samples for Screening ..................................................... 41 
8.2 
Immunogenicity Assessments ....................................................................... 42 
8.2.1 
Biological Samples............................................................................ 42 
8.2.2 
Laboratory Assays ............................................................................. 43 
8.2.3 
Immunological Read-Outs ................................................................ 44 
8.2.4 
Immunological Correlates of Protection ........................................... 44 
8.3 
Pre- and Post- Vaccination Procedures ....................................................... 45 
8.3.1 
Check Inclusion and Exclusion Criteria ............................................ 45 
8.3.2 
Body Temperature ............................................................................. 45 
8.3.3 
Pregnancy Testing ............................................................................. 45 
8.3.4 
Medical History ................................................................................. 45 
8.3.5 
Medication and Vaccine History ....................................................... 45 
8.3.6 
Post-Vaccination Observation Period ............................................... 46 
8.4 
Safety Assessments ........................................................................................ 46 
8.4.1 
Safety Laboratory Assessments ........................................................ 46 
8.4.2 
Study Holding Rules and Safety Monitoring .................................... 46 
8.5 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 47 
8.5.1 
Time Period and Frequency for Collecting AE, SAE, 
pIMD, MAE Information .................................................................. 47 
8.5.2 
Method of Detecting AEs and SAEs ................................................. 50 
8.5.3 
Treatment of Adverse Events ............................................................ 50 
8.5.4 
Follow-up of AEs and SAEs ............................................................. 50 
8.5.5 
Regulatory Reporting Requirements for SAEs and Other 
Events ................................................................................................ 50 
8.5.6 
Pregnancy .......................................................................................... 51 
8.5.7 
Adverse Events of Special Interest ................................................... 52 
8.5.8 
Participant Card ................................................................................. 53 
8.6 
Pharmacokinetics .......................................................................................... 53 

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10 
8.7 
Pharmacodynamics ....................................................................................... 53 
8.8 
Genetics .......................................................................................................... 53 
8.9 
Biomarkers ..................................................................................................... 53 
8.10 
Immunogenicity Assessments ....................................................................... 53 
8.11 
Health Economics .......................................................................................... 53 
9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 54 
9.1 
Statistical Hypotheses .................................................................................... 54 
9.2 
Sample Size Determination ........................................................................... 54 
9.3 
Analysis Sets ................................................................................................... 55 
9.3.1 
Criteria for Elimination from Analysis ............................................. 56 
9.4 
Statistical Analyses ........................................................................................ 56 
9.4.1 
General Considerations ..................................................................... 56 
9.4.2 
Participants Disposition .................................................................... 57 
9.4.3 
Primary Endpoint(s)/Estimand(s) Analysis....................................... 58 
9.4.4 
Secondary Endpoint(s) Analysis ....................................................... 60 
9.4.5 
Demography and Baseline Characteristic Analyses ......................... 60 
9.5 
Interim Analysis ............................................................................................. 61 
9.5.1 
Sequence of Analyses ....................................................................... 61 
9.5.2 
Statistical Consideration for Interim Analysis .................................. 62 
9.6 
Data Monitoring Committee......................................................................... 62 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 63 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 63 
10.1.1 
Regulatory and Ethical Considerations ............................................. 63 
10.1.2 
Adequate Resources .......................................................................... 64 
10.1.3 
Financial Disclosure .......................................................................... 64 
10.1.4 
Informed Consent Process................................................................. 64 
10.1.5 
Recruitment Strategy ......................................................................... 64 
10.1.6 
Data Protection .................................................................................. 65 
10.1.7 
Committees Structure ........................................................................ 65 
10.1.8 
Dissemination of Clinical Study Data ............................................... 66 
10.1.9 
Data Quality Assurance ..................................................................... 66 
10.1.10 Source Documents ............................................................................ 67 
10.1.11 Study and Site Start and Closure ....................................................... 68 
10.1.12 Publication Policy ............................................................................. 69 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 70 
10.3 
Appendix 3: FDA Toxicity Grading Scale ................................................... 71 
10.4 
Appendix 4: Management of Participants with Abnormal 
Laboratory Values ......................................................................................... 74 
10.5 
Appendix 5: AEs, SAEs, and pIMDs: Definitions and 
Procedures for Recording, Evaluating, Follow-up, and 
Reporting for Study Intervention ................................................................ 75 

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11 
10.5.1 
Definition of AE ................................................................................ 75 
10.5.2 
Definition of SAE ............................................................................. 77 
10.5.3 
Recording and Follow-Up of AE, SAE, and/or pIMD ...................... 78 
10.5.4 
Updating of SAE, pIMD, and Pregnancy Information after 
Removal of Write Access to the Participant’s eCRF ........................ 83 
10.5.5 
Reporting of SAEs ............................................................................ 83 
10.6 
Appendix 6: Contraceptive and Barrier Guidance and 
Collection of Pregnancy Information .......................................................... 85 
10.6.1 
Definitions ......................................................................................... 85 
10.6.2 
Contraception Guidance .................................................................... 85 
10.7 
Appendix 7: Abbreviations and Glossary of Terms ................................... 88 
10.8 
Appendix 8: List of Potential Immune-Mediated Diseases ........................ 94 
10.9 
Appendix 9: Protocol and Amendment History ....................................... 108 
11.0 
REFERENCES ........................................................................................................ 112 
 

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12 
LIST OF TABLES 
Table 1 
Schedule of Activities ....................................................................................... 18 
Table 2 
Interval Between Study Visits .......................................................................... 20 
Table 3 
Study Interventions Administered .................................................................... 32 
Table 4 
Laboratory Assays ............................................................................................ 43 
Table 5 
Immunological Read-Outs ................................................................................ 44 
Table 6 
Study Holding Rules ......................................................................................... 47 
Table 7 
Timeframes for Recording and Reporting Safety Information ........................ 49 
Table 8 
Timeframes for Submitting SAE, Pregnancy, pIMDs to IQVIA ..................... 51 
Table 9 
Analysis Sets .................................................................................................... 55 
Table 10 
Table of Laboratory Abnormalities .................................................................. 72 
Table 11 
Solicited Administration Site Events ................................................................ 75 
Table 12 
Solicited Systemic Events ................................................................................ 76 
Table 13 
Intensity Scales for Solicited Events in Adults 18 Years of Age or Older ....... 79 
Table 14 
Abbreviations ................................................................................................... 88 
Table 15 
Glossary of Terms ............................................................................................ 91 
Table 16 
GSK List of pIMD MedDRA Terms ................................................................ 94 
 
LIST OF FIGURES 
Figure 1 
Study Design .................................................................................................... 17 
Figure 2 
Screening and Safety Laboratory Schema ........................................................ 74 
 

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Protocol 219833 
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13 
1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title:  
A Phase I/II observer-blind, randomized, multi-center trial to evaluate the safety and 
immunogenicity of different formulations of monovalent Influenza 
A/Astrakhan/3212/2020-like (H5N8) virus vaccine with AS03 adjuvant system, given as a 
two-dose series to adults 18 to 64 years of age and 65 years of age and older. 
Rationale: 
The emergence of a novel reassortant influenza A (H5N8) virus in Russia in December 2020 
was associated with 7 human cases – none of which were symptomatic, and none resulted in 
death. However, this influenza virus was associated with a high mortality rate among birds. 
The likelihood of human infection is low at present, although previous infections in humans 
have been observed in China since 2014. The United States poultry population is currently 
experiencing a high number of avian flu cases, increasing the likelihood of an interspecies 
crossover event that will increase transmission and infection in humans. In any case, crossover 
events resulting in influenza strains capable of triggering epidemics like the 2009 swine flu 
epidemic are inevitable. The first human case of Highly Pathogenic Avian Influenza 
(HPAI)A(H5) virus in the United States was reported in late April 2022 and the virus has 
remained in wild bird flyways during the summer with the migrating birds already bringing it 
back into the country in fall 2022. This study tests a platform for H5N8 strains with the goal 
of providing additional public health preparedness and protection.  
Vaccination is the primary control measure against the spread of influenza virus infection in 
humans. Efforts are, therefore, underway to develop vaccines that could mitigate the impact of 
an H5N8 pandemic. GlaxoSmithKline (GSK) will produce an investigational 
AS03-adjuvanted influenza A/Astrakhan/3212/2020-like (H5N8) virus vaccine and will 
conduct a clinical trial to assess the immunogenicity and safety of different formulations of an 
H5N8 split virus vaccine manufactured in GSK Biologicals’ Québec facility, administered 
with AS03 adjuvant. 

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Objectives, and Endpoints: 
 
Objectives 
Endpoints (Population Summary) 
Primary 
Immunogenicity: 
To evaluate whether the monovalent influenza 
A/Astrakhan/3212/2020-like (H5N8) virus vaccine 
containing 3.75 µg, or 7.5 µg of HA with AS03A or 
AS03B elicits a HI response to the 
vaccine -homologous virus that meets or exceeds the 
US Food and Drug Administration, Center for 
Biologics Evaluation and Research immunogenicity 
criteria at the Day 43 visit. 
Humoral immune response in terms of: 
• 
Vaccine-homologous HI titers at Day 43 (i.e., 
GMT). 
• 
Vaccine-homologous HI titers increase at 
Day 43 compared to pre-vaccination (i.e., 
GMFR). 
• 
SP defined as titer ≥1:40 at Day 43 
(percentage of participants meeting SP 
criteria). 
Safety: 
To evaluate the safety and reactogenicity of the 
different vaccine formulations through the Day 43 
visit and SAEs and pIMDs through Day 43 and also 
6 months post dose 2. 
• 
Occurrence of each solicited administration 
site event during a 7-day follow-up period 
(i.e., day of vaccination and 6 subsequent 
days) after each vaccination (percentage of 
participants with occurrence). 
• 
Occurrence of each solicited systemic event 
during a 7-day follow-up (i.e., day of 
vaccination and 6 subsequent days) after 
each vaccination (percentage of participants 
with occurrence). 
• 
Occurrence of toxicity grade increase in 
either hematology or biochemistry 
laboratory tests 7 days after each vaccination 
(percentage of participants with change from 
baseline). 
• 
Occurrence of unsolicited AEs for 21 days 
(i.e., day of vaccination and 20 subsequent 
days) after each vaccination (percentage of 
participants with occurrence). 
• 
Occurrence of MAEs for 21 days (i.e., day of 
vaccination and 20 subsequent days) after 
each vaccination and also through 6 months 
post dose 2 (percentage of participants with 
occurrence). 
• 
Occurrence of SAEs until Day 43 and also 
6 months post dose 2 (percentage of 
participants with occurrence). 
• 
Occurrence of pIMDs until Day 43 and also 
6 months post dose 2 (percentage of 
participants with occurrence). 
Secondary 
To describe the vaccine-homologous (H5N8) HI 
profile in all study groups at Days 1, 22, 43, and 
6 months post dose 2. 
Vaccine-homologous (H5N8) HI titers for each study 
group: 

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Protocol 219833 
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Objectives 
Endpoints (Population Summary) 
• 
Vaccine-homologous HI titers at Day 1, 22, 
and 6 months post dose 2 (GMT). 
• 
Vaccine-homologous HI titers increase from 
pre-vaccination at Day 22 and 6 months post 
dose 2 (GMFR). 
• 
SP defined as titer ≥1:40 at Day 1, 22, and 
6 months post dose 2 (percentage of 
participants meeting SP criteria). 
• 
HI SC defined as titer ≥1:40 for participants 
with pre-vaccination titer below 1:10 or a 
≥4-fold increase from pre-vaccination titer 
for participants with pre-vaccination titer 
≥1:10 at Day 22, Day 43 and 6 months post 
dose 2 (percentage of participants meeting 
SC criteria). 
To describe the vaccine-homologous (H5N8) MN 
titers in a subset* of participants at Days 1, 22, and 
43, and 6 months post dose 2 
Vaccine-homologous (H5N8) MN titers for a subset 
of participants: 
• 
MN titers at Days 1, 22, and 43 and 
6 months post dose 2 (GMT). 
• 
Seropositivity rates defined as percentage of 
participants with reciprocal titer above 
LLOQ at Days 1, 22, 43, and 6 months post 
dose 2 (percentage of seropositive 
participants). 
• 
MN VR defined as titer ≥4× LLOQ for 
participants with pre-vaccination titer below 
LLOQ or a ≥4 -fold increase from 
pre-vaccination titer for participants with 
pre-vaccination titer ≥LLOQ at Days 22, 43, 
and 6 months post dose 2 (percentage of 
participants meeting VR criteria). 
 
Abbreviations: AE=adverse event; GMFR=geometric mean fold rise; GMT=geometric mean titer; 
HA=hemagglutinin; HI=hemagglutination inhibition; H5N8=monovalent influenza 
A/Astrakhan/3212/2020-like; LLOQ=lower limit of quantitation; MAE=medically attended adverse event; 
MN=microneutralization; pIMD=potential immune-mediated disease; SAE=serious adverse event; 
SC=seroconversion; SP=seroprotection; SPR=seroprotection rate; US=United States; VR=vaccine response. 
* Subset for Microneutralization testing will be performed on 50% of the participants, randomly selected and 
equally distributed across the different subgroups. 
 

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Overall Design: 
Number of Participants: 
This is a Phase I/II, observer-blind, randomized, age- stratified, multi-centric study with 
4 parallel groups, which will be conducted in the US. 
The study is planned to enroll approximately 520 participants randomly assigned to one of the 
4 dose groups. Each of the 4 groups will be stratified by age to create 8 subgroups of equal 
size in each dose group: 18 to 64 years of age (approximately 50% of participants enrolled) 
and 65 years of age and older (approximately 50% of participants enrolled). 
Intervention Groups and Duration: 
Each participant will receive 2 intramuscular doses of study vaccine 21 days apart. Each 
participant will participate for 6 months after receipt of the second dose administered. 
Study Groups (approximately 130 participants in each dose group):  
Dose 
Age Subgroup of Participants 
Number of Participants 
(Total =520) 
375_B: 3.75 µg HA and AS03B 
18 - 64 years of age 
≥65 years of age 
65 
65 
375_A: 3.75 µg HA and AS03A 
18 - 64 years of age 
≥65 years of age 
65 
65 
750_B: 7.5 µg HA and AS03B 
18 - 64 years of age 
≥65 years of age 
65 
65 
750_A: 7.5 µg HA and AS03A 
18 - 64 years of age 
≥65 years of age 
65 
65 
All the participants will have screening laboratory tests to determine eligibility for the study. 
The first 50% of enrolled participants in each age and dose group will be required to have 
on-site visits for safety laboratory tests 7 days after each vaccination (i.e., Visit 2 and Visit 4). 
All other participants will have a remote visit (e.g., telephone call, video call, email, or text 
communication) with the site. 
Data Monitoring/Other Committee: None 
Safety Monitoring: The study will be conducted with an internal Safety Review Committee.  
 

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1.2 
Study Design 
Figure 1 
Study Design 
 
 
 
 Abbreviations: AE=adverse event; EOS=end of study; immuno=immunogenicity blood draw; iSRC=internal 
safety review committee; MAE=medically attended adverse event; pIMD=potential immune-mediated 
disease; SAE=serious adverse event.  
 

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1.3 
Schedule of Activities 
Table 1 
Schedule of Activities 
Time points 
Screening 
Visit 
Visit 11 
Visit 22 
Visit 31 
Visit 42 
Visit 5 
Visit 6/EOS 
 
 
Day 1 
Dose 1 
Day 8-10 
Day 22 
Dose 2 
Day 29-31 Day 43 
6 months post 
dose 2 
Informed consent 
● 
 
Check inclusion/exclusion criteria 
● 
● 
● 
Collect demographic data 
● 
 
Study group and treatment number allocation 
 
O 
Treatment number allocation for subsequent dose 
O 
Recording of administered treatment number 
 
● 
● 
Blood sampling for hematology and biochemistry safety tests (approx. 
10 mL for screening and approx. 6 mL for post-vaccination tests)3 
● 
 
●2 
 
●2 
Blood sampling for immunogenicity assessments and HI/MN assay 
development/validation and samples for BARDA4 (40 mL) 
 
●1 
 
●1 
 
● 
● 
Vaccine administration 
 
● 
● 
30-minute observation period after each vaccine administration 
 
● 
● 
Medical history 
● 
● 
Physical examination5 
● 
 
Vaccination history 
● 
● 
Urine pregnancy test to be performed prior to each vaccination (women of 
childbearing potential only) 
 
● 
● 
Check contraindications and warnings and precautions to vaccination 
 
● 
● 
Pre-vaccination body temperature 
 
● 
● 

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Time points 
Screening 
Visit 
Visit 11 
Visit 22 
Visit 31 
Visit 42 
Visit 5 
Visit 6/EOS 
 
 
Day 1 
Dose 1 
Day 8-10 
Day 22 
Dose 2 
Day 29-31 Day 43 
6 months post 
dose 2 
Record any concomitant medication/vaccination 
● 
● 
● 
● 
● 
Distribution of diary cards 
 
O 
O 
Recording of solicited events (Up to 7 days after each vaccination) 
 
● 
● 
Recording of unsolicited adverse events (Up to 21 days after each 
vaccination) 
 
● 
● 
● 
● 
● 
Return of diary cards 
O 
O 
O 
O 
Diary card transcription by investigator or delegate 
 
 
●6 
● 
●6 
● 
 
Reporting of SAEs, pIMDs, MAEs, pregnancies 
 
● 
● 
● 
● 
● 
● 
Study Conclusion 
● 
Abbreviations: BARDA=Biomedical Advanced Research and Development Authority; eCRF=electronic case report form; EOS=end of study; FDA=Food and 
Drug Administration; HI=hemagglutination inhibition; MAE=medically attended adverse event; MN=microneutralization; pIMD=potential immune-mediated 
disease; SAE=serious adverse event. 
Note: the double-line borders indicate analyses which will be performed on all data obtained up to those time points. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
0 is used to indicate a study procedure that does not require documentation in the individual eCRF. 
1 All Day 1 and Day 22 activities, including blood draw, are to be performed prior to vaccine administration. 
2 The first 50% of study participants in each age and dose group will be required to have safety laboratory assessments performed at the clinic 7-days post each 
vaccination (i.e., Visit 2 and Visit 4). All other participants will have a remote visit (e.g., telephone call, video call, email, or text communication) with the 
site. 
3 See Table 10 for applicable laboratory assessments. 
4 Participant will be asked in Informed Consent Form for permission for future use of blood samples, including use by BARDA. 
5 A physical examination based on medical history will be performed at the Screening Visit. Physical examination at each study visit after the study intervention 
administration visit will be performed only if the participant/participant’s caregiver(s) indicates during questioning that there might be some underlying 
pathology(ies) or if deemed necessary by the investigator or delegate. 
6 Participants required to have safety laboratory measurements at Visits 2 and 4 will also have the initial data from their diary cards transcribed and then the diary 
card returned to them during these visits. All other participants will return their diary cards and have them transcribed on Visits 3 and 5.

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Table 2 
Interval Between Study Visits 
Interval 
Planned visit interval 
Allowed interval range 
Screening →Visit 1 
Up to 14 days 
14 days 
Visit 1 →Visit 2 
7 days 
7-9 days 
Visit 1 →Visit 3 
21 days 
14-35 days  
Visit 3 →Visit 4 
7 days 
7-9 days  
Visit 3 →Visit 5 
21 days 
14-35 days  
Visit 3 →Visit 6 
180 days post dose 2 
165-195 days 

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2.0 INTRODUCTION 
2.1 
Study Rationale 
Novel influenza A viruses, including subtypes H5N1, H3N2v, H9N2, A(H1N1) pdm09, H7N9 
and H5N8, continue to emerge and infect humans; therefore, it is imperative that preparation 
be maintained for the next influenza pandemic. 
The US National Pre-Pandemic Influenza Vaccine Stockpile contains various influenza virus 
vaccines, including influenza A(H5) and A(H7) virus vaccines, as well as adjuvants, including 
AS03, for administration with the vaccine antigens to improve the immunogenicity and 
achieve antigen dose-sparing. 
The emergence of a novel reassortant influenza A (H5N8) virus in Russia in December 2020 
was associated with 7 human cases – none of which were symptomatic or associated with any 
deaths. However, this influenza virus was associated with a high mortality rate among birds.1 
The likelihood of human infection is low at present, although previous infections in humans 
have been observed in China since 2014.2 The United States poultry population is currently 
experiencing a high number of avian flu cases, increasing the likelihood of an interspecies 
crossover event that will increase transmission and infection in humans. In any case, crossover 
events resulting in influenza strains capable of triggering epidemics like the 2009 swine flu 
epidemic are inevitable. This study tests a platform for H5N8 strains with the goal of 
providing additional public health preparedness and protection.3 
The first human case of Highly Pathogenic Avian Influenza (HPAI)A(H5) virus in the United 
States was reported in late April 2022 and the virus has remained in wild bird flyways during 
the summer with the migrating birds already bringing it back into the country in fall 2022.4 
Therefore, it is crucial that preparation be maintained to enable rapid and successful process 
scale-up for commercial scale production if needed for an event. Antigenic analyses indicate 
that the candidate vaccine virus (CVV) A/Astrakhan/3212/2020-like (H5N8) influenza virus 
cross-reacts with the most recent A(H5) viruses from wild birds and poultry in the US, 
Europe, Africa, and Asia. 
Vaccination is the primary control measure against the spread of influenza virus infection in 
humans. Efforts are, therefore, underway to develop vaccines that could mitigate the impact of 
an H5N8 pandemic. GSK will produce an investigational AS03-adjuvanted influenza 
A/Astrakhan/3212/2020-like (H5N8) virus vaccine and will conduct a clinical trial to assess 
the immunogenicity and safety of different formulations of an H5N8 split virus vaccine 
manufactured in GSK Biologicals’ Québec facility, administered with AS03 adjuvant. 

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2.2 
Background 
Given the emergence of new influenza variants of concern and the ongoing need to match 
variants with vaccines, there is a critical need to ensure timely development of a H5N8 
influenza vaccine. 
Earlier studies have shown that the pandemic influenza vaccines administered with AS03 
adjuvant had a similar safety profile wherein most of the adverse events occur around the time 
of vaccination. Review of data from these studies also suggests a favorable safety profile for 
adults over 65 years of age. 
Furthermore, Biomedical Advanced Research and Development Authority (BARDA), in 
collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), has 
previously conducted 3 clinical studies (DMID 15-0064, DMID 15-0066, BARDA BPI 
16005) using a non-GSK H5N8 antigen in combination with varying doses of either MF59 or 
GSK’s AS03 as an adjuvant. These so-called ‘mix and match’ studies were completed in 
2020, with DMID 15-0064 and 15-0066 together enrolling approximately 664 participants, of 
which 264 received an AS03-containing vaccine. The BPI 16005 study assessed the safety and 
immunogenicity of a homologous or heterologous vaccination series with inactivated 
monovalent influenza H5 vaccines (H5N1 and H5N8) and enrolled 720 participants. Data 
from these studies have showed that the vaccines were well tolerated in terms of safety 
profiles (follow-up period of up to 12 months period for the DMID studies and up to 
17 months for the BARDA study). In terms of immunogenicity, these studies demonstrated 
that to achieve adequate immune responses, two doses of vaccines were required, and the 
immunogenicity was enhanced by the addition of AS03A adjuvant.5,6 
GSK is planning to conduct a Phase I/II observer-blind, randomized, multi-center trial in 2023 
to evaluate the safety and immunogenicity of different formulations of monovalent Influenza 
A/Astrakhan/3212/2020-like (H5N8) virus vaccine with the AS03 adjuvant system, given as a 
two-dose series to adults 18 to 64 years of age and 65 years of age and older. 
2.3 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of the study intervention may be found in the Investigator’s 
Brochure (IB). 
The Sponsor will immediately notify the Principal Investigator (PI) if any additional safety or 
toxicology information becomes available during the study. 
This study will be performed in compliance with the protocol, International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good 

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Clinical Practice (GCP), European Union Clinical Trials Regulation (EU CTR), and 
applicable regulatory requirements. 
 
 

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24 
3.0 OBJECTIVES, AND ENDPOINTS 
Objectives 
Endpoints (Population Summary) 
Primary 
Immunogenicity: 
To evaluate whether the monovalent influenza 
A/Astrakhan/3212/2020-like (H5N8) virus 
vaccine containing 3.75 µg, or 7.5 µg of HA with 
AS03A or AS03B elicits a HI response to the 
vaccine-homologous virus that meets or exceeds 
the US Food and Drug Administration, Center for 
Biologics Evaluation and Research 
immunogenicity criteria at the Day 43 visit. 
Humoral immune response in terms of: 
• 
Vaccine-homologous HI titers at Day 43 (i.e., 
GMT). 
• 
Vaccine-homologous HI titers increase at Day 
43 compared to pre-vaccination (i.e., GMFR). 
• 
SP defined as titer ≥1:40 at Day 43 
(percentage of participants meeting SP 
criteria). 
Safety: 
To evaluate the safety and reactogenicity of the 
different vaccine formulations through the Day 43 
visit and SAEs and pIMDs through Day 43 and 
also to 6 months post dose 2 
• 
Occurrence of each solicited administration 
site event during a 7-day follow-up period 
(i.e., day of vaccination and 6 subsequent 
days) after each vaccination (percentage of 
participants with occurrence). 
• 
Occurrence of each solicited systemic event 
during a 7-day follow-up (i.e., day of 
vaccination and 6 subsequent days) after each 
vaccination (percentage of participants with 
occurrence). 
• 
Occurrence of toxicity grade increase in 
either hematology or biochemistry laboratory 
tests 7 days after each vaccination 
(percentage of participants with change from 
baseline). 
• 
Occurrence of unsolicited AEs for 21 days 
(i.e., day of vaccination and 20 subsequent 
days) after each vaccination (percentage of 
participants with occurrence). 
• 
Occurrence of MAEs for 21 days (i.e., day of 
vaccination and 20 subsequent days) after 
each vaccination and also through 6 months 
post dose 2 (percentage of participants with 
occurrence). 
• 
Occurrence of SAEs until Day 43 and also 
6 months post dose 2 (percentage of 
participants with occurrence). 
• 
Occurrence of pIMDs until Day 43 and also 
6 months post dose 2 (percentage of 
participants with occurrence). 

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Objectives 
Endpoints (Population Summary) 
Secondary 
To describe the vaccine-homologous (H5N8) HI 
profile in all study groups at Days 1, 22, 43, and 
6 months post dose 2. 
Vaccine-homologous (H5N8) HI titers for each study 
group: 
• 
Vaccine-homologous HI titers at Day 1, 22, 
and 6 months post dose 2 (GMT). 
• 
Vaccine-homologous HI titers increase from 
pre-vaccination at Day 22, and 6 months post 
dose 2 (GMFR). 
• 
SP defined as titer ≥1:40 at Day 1, 22, and 
6 months post dose 2 (percentage of 
participants meeting SP criteria). 
• 
HI SC defined as titer ≥1:40 for participants 
with pre-vaccination titer below 1:10 or as a 
≥4-fold increase from pre-vaccination titer for 
participants with pre-vaccination titer ≥1:10 
at Day 22, Day 43 and 6 months post dose 2 
(percentage of participants meeting SC 
criteria). 
To describe the vaccine-homologous (H5N8) MN 
titers in a subset* of participants at Days 1, 22, and 
43, and 6 months post dose 2 
Vaccine-homologous (H5N8) MN titers for a subset of 
participants: 
• 
MN titers at Days 1, 22, and 43 and 6 months 
post dose 2 (GMT). 
• 
Seropositivity rates defined as percentage of 
participants with reciprocal titer above LLOQ 
at Days 1, 22, 43, and 6 months post dose 2 
(percentage of seropositive participants). 
• 
MN VR defined as titer ≥4×LLOQ for 
participants with pre-vaccination titer below 
LLOQ or a ≥4 -fold increase from 
pre-vaccination titer for participants with 
pre-vaccination titer ≥LLOQ at Days 22, 43, 
and 6 months post dose 2 (percentage of 
participants meeting VR criteria). 
 
Abbreviations: AE=adverse event; GMFR=geometric mean fold rise; GMT=geometric mean titer; 
HA=hemagglutinin; HI=hemagglutination inhibition; H5N8=monovalent influenza 
A/Astrakhan/3212/2020-like; LLOQ=lower limit of quantitation; MAE=medically attended adverse event; 
MN=microneutralization; pIMD=potential immune-mediated disease; SAE=serious adverse event; 
SC=seroconversion; SP=seroprotection; US=United States; VR=vaccine response. 
* Subset for Microneutralization testing will be performed on 50% of the participants, randomly selected and 
equally distributed across the different subgroups 
Note that complementary details on estimand such as impact of intercurrent events on the 
analysis can be found in Section 9.0. 

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4.0 STUDY DESIGN 
4.1 
Overall Design 
The Study Design is provided in Figure 1. The Schedule of Activities is provided in Table 1. 
This is a Phase I/II, observer-blind, randomized, age- stratified, multi-centric study with 
4 parallel groups, which will be conducted in the US. 
The study is planned to enroll approximately 520 participants randomly assigned to one of the 
4 dose groups. Each of the 4 groups will be stratified by age to create 8 subgroups of equal 
size in each dose group: 18 to 64 years of age (approximately 50% of participants enrolled) 
and 65 years of age and older (approximately 50% of participants enrolled). 
Each participant will receive 2 intramuscular doses of study vaccine 21 days apart. Each 
participant will participate for 6 months after receipt of the second dose administered. 
Study Groups (approximately 130 participants in each dose group):  
Dose  
Age Subgroup of 
Participants 
Number of Participants 
(Total =520) 
375_B: 3.75 µg HA and AS03B 
18 - 64 years of age 
≥65 years of age 
65 
65 
375_A: 3.75 µg HA and AS03A 
18 - 64 years of age 
≥65 years of age 
65 
65 
750_B: 7.5 µg HA and AS03B 
18 - 64 years of age 
≥65 years of age 
65 
65 
750_A: 7.5 µg HA and AS03A 
18 - 64 years of age 
≥65 years of age 
65 
65 
All the participants will have screening laboratory tests to determine eligibility for the study. 
The first 50% of enrolled participants in each age and dose group will be required to have 
on-site visits for safety laboratory tests 7 days after each vaccination (i.e., Visit 2 and Visit 4). 
All other participants will have a remote visit (e.g., telephone call, video call, email, or text 
communication) with the site. 
This study will be conducted with oversight by an internal Safety Review Committee (iSRC). 
See Section 10.1.7 for iSRC structure.  
4.2 
Scientific Rationale for Study Design 
Novel influenza A viruses, including subtypes H5N1, H3N2v, H9N2, A(H1N1) pdm09, H7N9 
and H5N8, continue to emerge and infect humans; therefore, it is imperative that preparation 
be maintained for the next influenza pandemic. The US National Pre-Pandemic Influenza 
Vaccine Stockpile contains various influenza virus vaccines, including influenza A(H5) and 
A(H7) virus vaccines, as well as adjuvants, including AS03, for administration with the 

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27 
vaccine antigens to improve the immunogenicity and achieve antigen dose-sparing. The 
rationale for the study design is such that it allows the assessment of antigen sparing by 
varying the amount of adjuvant present, as well as assessing the effect of a change in antigen 
dose. It also further assesses any difference in immune response or safety profile in an older 
population (>65 years old) compared to a younger age subgroup (18 to 64 years old).  
4.3 
Justification for Dose 
The rationale for evaluating 3.75 g and 7.5 g doses of the H5N8 antigen is based on the 
BARDA’s requirement to assess the dose-sparing ability of full or half doses of AS03 in 
combination with Influenza A/Astrakhan/3212/2020-like (H5N8) virus vaccine, as well as 
previous experience with AS03 containing pandemic influenza vaccines. GSK has previously 
evaluated both 3.75 g and 7.5 g antigen doses in combination with the AS03 adjuvant in 
development of the H5N1 and H7N9 vaccines with a positive risk/benefit. 
AS03A (11.86 mg tocopherol) and AS03B (5.93 mg tocopherol) will be evaluated in this study, 
since both AS03 formulations have been shown to improve the immunogenicity of inactivated 
split-virion H5N1 and H7N9 pandemic influenza vaccines in studies conducted by GSK.7-14  
Further information on dose justification for this study can be found in the IB.  
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she returned for the last visit as 
described in this protocol. 
End of Study (EOS) is the last subject last visit (LSLV) (contact at 6 months post -last dose) 
or date of the last testing/reading released of the Human Biological Samples or imaging data, 
related to primary and secondary endpoints, whichever occurs later. End of study must be 
achieved no later than 8 months after LSLV. End of study cannot be before LSLV. 
4.5 
Study Stopping Criteria 
Study stopping criteria is not applicable for this study. See holding rules in Section 8.4. 

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28 
5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Medically stable participants as established by medical history and clinical examination 
before entering into the study. (e.g., eligible participant should have no new diagnosis, 
escalation of treatment, or change in medication in the preceding 3 months). 
2. A male or female ≥18 years of age at the time of signing consent form. 
3. 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, and return the diary cards in a timely manner). 
4. Written or witnessed/thumb printed informed consent obtained from the participant 
prior to performance of any study specific procedure. 
5. Female participants of childbearing potential or non-childbearing potential may be 
enrolled in the study if specific criteria are met. See Section 5.2.3 for details. 
 
5.2 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
5.2.1 
Medical Conditions 
1. Current diagnosis or history of autoimmune disorder(s) except hypothyroidism due to 
Hashimoto’s thyroiditis. See Section 8.5.7.1. 
2. History of any reaction or hypersensitivity likely to be exacerbated by any component 
of the vaccine (including egg products). 
3. Clinically significant acute or chronic pulmonary, cardiovascular, hepatic, or renal 
disease that appears uncontrolled or untreated, as determined by history or physical 
examination. 
4. Any confirmed or suspected immunosuppressive or immunodeficient condition, based 
on medical history, physical examination, or abnormalities in screening blood tests. 
5. Recurrent history of or uncontrolled neurological disorders or seizures. 
6. History of Guillain-Barré syndrome. 
7. Diagnosed with cancer, or treatment for cancer within 3 years. 
o Persons with a history of cancer who are disease-free without treatment for 3 years 
or more are eligible. 

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29 
o Persons with a history (within last 3 years) of histologically-confirmed basal cell 
carcinoma of the skin successfully treated with local excision only, are accepted 
and are eligible, but other histologic types of skin cancer are exclusionary. 
o Women who are disease-free 3 years or more after treatment for breast cancer and 
receiving long-term prophylaxis (for example, with tamoxifen) are eligible. 
8. Documented human immunodeficiency virus-positive participants. 
9. Bedridden participants. 
10. Personal or family history of narcolepsy. 
11. FDA toxicity Grade 2 (Section 10.3), or greater, laboratory tests at Screening 
(Section 1.3). 
12. Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study. 
5.2.2 
Prior/Concomitant Therapy 
13. Use of any investigational or non-registered product (drug, vaccine, or medical device) 
other than the study vaccine during the period beginning 30 days before the first dose 
of study vaccine (Day -29 to Day 1), or planned use during the entire study period. 
14. Use of public health emergency vaccines like COVID-19, Monkey pox (mpox) etc. 
These can be given at any time, but there should a gap of 2 weeks before a dose of 
study vaccine can be given. 
15. Use of any licensed vaccines: prior to receipt of the study vaccine (2 weeks for 
inactivated vaccines and 4 weeks for live vaccines) and continuing up to 3 weeks after 
receiving the dose 2 of study vaccine. 
16. Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g., infliximab). 
17. Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study vaccine or planned 
administration during the study period. 
18. Chronic administration (defined as more than 14 days in total) of immunosuppressants 
or other immune-modifying drugs during the period starting 3 months prior to the first 
vaccine dose and through the entire study period. For corticosteroids, this will mean 
prednisone equivalent ≥20 mg/day for 14 days or a total of ≥280 mg of prednisone 
equivalent dose in any 14-day period. Inhaled and topical steroids are allowed. 
5.2.3 
Other Exclusions 
19. Pregnant or lactating female. 
20. Female planning to become pregnant or planning to discontinue contraceptive 
precautions within 2 months after completion of the vaccination series. 

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21. History of/or current drug/alcohol abuse. 
22. Any study personnel or their immediate dependents, family, or household member. 
23. Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device). 
 
5.3 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical study is 
not subsequently randomly assigned to study intervention/entered in the study. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials publishing requirements 
and to respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, and any serious adverse event (SAE). 
5.4 
Criteria for Temporarily Delaying Enrollment and Vaccination 
Vaccination may be postponed within the allowed time interval (Table 2) until transient 
circumstances cited below have been resolved: 
• Acute disease and/or fever at the time of each vaccination: Fever is defined as a 
temperature of or above 38.0°C/100.4°F. The preferred route for measuring temperature in 
this study will be oral. Participants with a minor illness (such as mild diarrhea, mild upper 
respiratory infection) without fever may be enrolled at the discretion of the investigator. 
• Use of antipyretics/analgesics (e.g., acetaminophen and non-steroidal anti-inflammatory 
drugs [NSAIDs]) and/or antibiotics within 3 days prior to vaccination. Low-dose aspirin 
(81 mg daily) regimen is permitted. 
• Use of public health emergency vaccines like COVID-19, Monkey pox etc. These can be 
given at any time, but there should a gap of 2 weeks before a dose of study vaccine can be 
given. 
 

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31 
6.0 STUDY INTERVENTIONS AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), intended to be 
administered to a study participant according to the study protocol.  

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6.1 
Study Interventions Administered 
 
Table 3 
Study Interventions Administered 
Study 
intervention 
Name: 
3.75 µg HA + AS03B ** 
3.75 µg HA + AS03A * 
7.5 µg HA + AS03B ** 
7.5 µg HA + AS03A * 
Vaccine 
Product Name: 
FLU Q-PAN 
H5N8 (3.75) 
AS03B 
FLU Q-PAN 
H5N8 (3.75) 
AS03A 
FLU Q-PAN 
H5N8 (7.5) 
AS03B 
FLU Q-PAN 
H5N8 (7.5) 
AS03A 
Presentation: 
Suspension for 
emulsion for 
injection in vial 
Emulsion 
for emulsion 
for injection 
in vial 
Suspension for 
emulsion for 
injection in vial 
Emulsion 
for emulsion 
for injection 
in vial 
Suspension for 
emulsion for 
injection in vial 
Emulsion 
for emulsion 
for injection 
in vial 
Suspension for 
emulsion for 
injection in vial 
Emulsion 
for emulsion 
for injection 
in vial 
Vaccine 
Product 
Formulation 
(refer to 
Pharmacy 
Manual): 
A/Astrakhan/32
12/2020-like 
(H5N8) (3.75 
µg HA); Water 
for injection q.s. 
AS03B: DL-
α-tocopherol 
and squalene 
in an o/w 
emulsion 
(5.93 mg 
DL-α-
tocopherol); 
Water for 
injection q.s. 
A/Astrakhan/32
12/2020-like 
(H5N8) (3.75 
µg HA); Water 
for injection q.s. 
AS03A: DL-
α-tocopherol 
and squalene 
in an o/w 
emulsion 
(11.86 mg 
DL-α-
tocopherol); 
Water for 
injection q.s. 
A/Astrakhan/32
12/2020-like 
(H5N8) (7.5 µg 
HA); Water for 
injection q.s. 
AS03B: DL-
α-tocopherol 
and squalene 
in an o/w 
emulsion 
(5.93 mg 
DL-α-
tocopherol); 
Water for 
injection q.s. 
A/Astrakhan/32
12/2020-like 
(H5N8) (7.5 µg 
HA); Water for 
injection q.s. 
AS03A: DL-
α-tocopherol 
and squalene 
in an o/w 
emulsion 
(11.86 mg 
DL-α-
tocopherol); 
Water for 
injection q.s. 
Volume to be 
Administered: 
0.25 mL 
0.5 mL 
0.375 mL 
0.5 mL 
Number of 
Doses to be 
Administered: 
2 
2 
2 
2 
Route of 
Administration: 
Intramuscular use 
Administration Site: 

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Location: 
Deltoid 
Directionality: 
Not applicable 
Laterality***: 
Non-dominant 
Packaging and 
Labeling****: 
Refer to Pharmacy Manual for more details 
Manufacturer: 
GSK Biologicals SA 
Type of 
contact/Time 
points: 
Visit 1 (Day 1), Visit 3 (Day 22) 
Abbreviations: HA=hemagglutinin o/w=oil/water; q.s.=quantity sufficient. 
* The AS03A doses will be prepared using adjuvant vialed at a concentration of 47.44 mg/mL tocopherol. The final AS03A doses will contain 11.86 mg 
tocopherol. 
** The AS03B doses will be prepared as half a dilution of AS03A (with AS03A vialed at concentration of 47.44 mg/mL). 
*** The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine in the non-dominant arm, an injection in the 
dominant arm may be performed. 
****Labeling is compliant with the requirements of applicable regulatory agencies. 
 

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6.2 
Preparation, Handling, Storage, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit and storage for all study intervention received, and any 
discrepancies are reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention, and only authorized 
study site staff may supply or administer study intervention.  
All study intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized study site staff. 
The investigator is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
The investigator, a member of the study site staff, or a hospital pharmacist must maintain an 
adequate record of the receipt, distribution, and storage temperature of the study vaccine using 
the Drug Accountability Form. These forms must be available for inspection at any time. 
Further guidance and information for the storage, handling, and final disposition of study 
interventions are provided in the Pharmacy Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally assigned to randomized study intervention using an 
interactive web response system (IWRS). The randomization will be stratified by age 
subgroup and use a permutation blocking scheme. Before the study is initiated, the log-in 
information and directions for the IWRS will be provided to each study site. 
Data will be collected in an observer-blind manner. The investigator(s), their staff and the 
participants will not be aware of the study intervention assignment. The study intervention 
will be prepared and administered by qualified study personnel who can be aware of the 
intervention assignment. The number of each intervention kit will be recorded in the eCRF. 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There will be 
no link between the study intervention and the identity of the participant. 
GSKs Global Safety staff may unblind the intervention assignment for any participant with an 
SAE. If the SAE requires that an expedited regulatory report be sent to one or more regulatory 
agencies, a copy of the report, identifying the participant’s intervention assignment, may be 
sent to investigators in accordance with local regulations and/or GSK policy. 

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6.4 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and the eCRF. See 
Section 8.3 for pre- and post-vaccination procedures. 
6.5 
Dose Modification 
Dose modifications are not applicable for this study. 
6.6 
Continued Access to Study Intervention After the End of the Study 
Not applicable for this study.  
6.7 
Treatment of Overdose 
For this study, an overdose is any dose of study intervention given to a participant that 
exceeds the maximum study dose for a single vaccination. 
GSK does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should: 
• Contact the medical monitor immediately. 
• Evaluate the participant to determine, in consultation with the medical monitor, whether 
study intervention should be interrupted or whether the subsequent dose should be 
reduced. 
6.8 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) or other specific categories of interest that the 
participant is receiving at the time of enrollment or receives during the study must be recorded 
along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
• Route of administration 
• For vaccines (if applicable) include brand name and manufacturer (plus lot number if 
available) 
Concomitant therapy that meets the exclusionary criteria for this study is listed in 
Section 5.2.2. 

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The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  
 

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7.0 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific study sites or of the study as a whole are detailed in 
Section 10.1.11. 
7.1 
Discontinuation of Study Intervention 
Discontinuation of study intervention refers to any participant who has received the first dose 
and has not received the second dose of study intervention. A participant who discontinued 
study intervention may continue other study procedures (e.g., safety assessment or 
immunogenicity testing), 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 (i.e., SAE, potential immune-mediated disease [pIMD]) 
• Unsolicited non-serious AE  
• Safety laboratory assessment results that are Grade 2 (moderate) or greater based on FDA 
toxicity grading that did not resolve, after repeat testing, to FDA toxicity Grade 1 or less 
(Figure 2) 
• Solicited event 
• Protocol Deviation 
• Not willing to be vaccinated 
• Pregnancy 
• Inappropriate enrollment 
• Other (specify) 
It may be necessary for a participant to permanently discontinue study intervention. If study 
intervention is permanently discontinued, the participant will be encouraged to remain in the 
study to be evaluated for post- dose visits and for safety follow-up. See the Schedule of 
Activities (SoA) in Section 1.3 for data to be collected at the time of discontinuation of study 
intervention and follow-up and for any further evaluations that need to be completed. 
Participants who discontinue study intervention will not be replaced. 
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 or criteria listed in Sections 5.2.1 and 
5.2.2 should not receive additional doses of study intervention. Such participants should be 
encouraged to continue other study procedures. All relevant criteria for discontinuation of 
study intervention administration must be recorded in the eCRF. 
• Participants who experience any SAE judged to be possibly or probably related to study 
intervention or non-study concomitant vaccine/product, including hypersensitivity 
reactions. 
• Participants who develop any new condition which, in the opinion of the investigator, may 
pose additional risk to the participants if they continue to participate in the study. 
• Anaphylaxis following the administration of study interventions. 
• Any condition that in the judgment of the investigator would make intramuscular injection 
unsafe. 
• Occurrence of a new pIMD that, in the opinion of the investigator, exposes the participant 
to unacceptable risk from subsequent vaccination. In such cases, the investigator should 
use their clinical judgment prior to administering the next dose of the study interventions. 
Refer to Section 8.5.7.1 for the definition of pIMD. 
• Pregnancy. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request for any reason 
(or without providing any reason) or may be withdrawn at any time at the discretion of the 
investigator for safety, behavioral, or compliance reasons. 
Participants who discontinue study intervention or withdrawn from the study due to a safety 
issue are required to have a follow-up visit to monitor the status of the safety issue. Otherwise, 
the participant will be permanently discontinued from the study intervention and the study at 
that time. 
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. If the participant withdraws consent for 
disclosure of future information, the Sponsor may retain and continue to use any data 
collected before such a withdrawal of consent. 
If a participant withdraws from the study, the participant may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study records. 
The primary reason for study withdrawal will be documented in the eCRF based on the list 
below: 
• AE requiring expedited reporting (i.e., SAE, pIMD) 

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• Unsolicited non-serious AE 
• Solicited events 
• Protocol deviation 
• Withdrawal by participant, not due to an AE* 
• Migrated/Moved from the study area 
• Lost to follow-up 
• Sponsor study termination 
• Inappropriate enrollment 
• Other (specify) 
*If a participant is withdrawn from the study because he/she has withdrawn consent and 
provided the reason for its withdrawal, the investigator must document this reason in the 
eCRF. 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will follow 
participants who are withdrawn from the study as result of an SAE/AE until the event is 
resolved (see Section 10.5.3). 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The study site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers 
or exemptions are not allowed. 
Immediate safety concerns should be discussed with IQVIA immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures and associated data conducted as part of the participant’s routine clinical 
management (e.g., blood count) and obtained before signing of the informed consent form 
(ICF) may be utilized for screening or baseline purposes provided the procedures met the 
protocol-specified criteria and were performed within the timeframe defined in the SoA 
(Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 240 mL.  
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples (e.g., hemolyzed sample). Only one sample per timepoint should be sent to the 
laboratory for testing. 
8.1 
Screening Procedures 
8.1.1 
Informed Consent 
The signed informed consent of the participant must be obtained before study participation. 
Refer to Section 10.1.4 for the requirement on how informed consent will be obtained.  
8.1.2 
Check Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be checked as described in Sections 5.1 and 5.2 at 
Screening Visits and before dosing on Visit 1 and Visit 3. 
8.1.3 
Collection of Demographic Data 
Demographic data according to local regulations such as date of birth, sex, race*, ethnicity*, 
and occupation will be collected in the eCRF. Collection of sex, race, and ethnicity data is 

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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. 
*Differences in the safety and efficacy of certain medical products, including vaccines, have 
been observed in racially and ethnically distinct subgroups.18-20 These differences may be 
attributable to intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., 
diet, environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 
8.1.4 
Medical History 
The participant’s medical history will be obtained by interviewing the participant and a review 
of the participant’s available medical records. Any relevant pre-existing conditions, signs 
and/or symptoms present prior to the study intervention will be recorded in the eCRF. 
8.1.5 
Physical Examinations 
Physical examination will be performed for each participant. 
If the investigator determines that the participant’s health on the day of study intervention 
administration temporarily precludes dosing, the visit will be rescheduled. Refer to the 
Section 5.4 for the list of criteria for temporary delay of study intervention administration. 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate health 
care provider. 
Physical examination at each study visit after the Screening Visit will be performed only if the 
participant/participant’s caregiver(s) indicates during questioning that there might be some 
underlying pathology(ies) or if deemed necessary by the investigator or delegate. 
8.1.6 
Medication and Vaccination History 
The participant’s medication and vaccination history will be obtained by interviewing the 
participant and review of the participant’s available medical records. 
Participant’s vaccination history for prior 3 years should be collected. 
8.1.7 
Biological Samples for Screening 
A volume of approximately 10 mL whole blood will be collected at the Screening Visit for the 
following laboratory assessments: Hematology: complete blood count with differential and 
platelet count; Chemistry/metabolic panel: Sodium, Potassium, Creatinine, Alanine 
aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline Phosphatase, total 
bilirubin, and blood urea nitrogen (BUN). These laboratory assessments will be performed 

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locally at the site. Participants with laboratory assessment results of FDA toxicity Grade 1 or 
lower will be considered eligible to participate in the study (Section 10.3). 
8.2 
Immunogenicity Assessments 
Collected biological samples will be used for protocol-mandated research and purposes related 
to the improvement, development, validation, and quality assurance of the laboratory tests 
described in this protocol and for transfer of sera samples to BARDA for future use, for those 
participants who consented their samples be utilized for further research. 
Future findings may make it desirable to use the samples acquired in this study for future 
research not described in this protocol. All participants will be asked to give a specific consent 
to allow Sponsor or a contracted partner to use the samples for future research. 
Future research will be subjected to prior Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB) approval if required per local legislation. 
Information on further investigations and their rationale can be obtained from Sponsor. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
If additional testing is performed, the marker priority ranking given in Section 8.2.3 may be 
changed. 
Collected samples will be stored at GSK for a maximum of 20 years. Samples at BARDA may 
be stored for 20 years and beyond. This storage period begins when the last participant 
performed the last study visit, unless local rules, regulations or guidelines require different 
timeframes or procedures, which would then be in line with participant consent. These extra 
requirements need to be communicated formally, discussed, and agreed to with GSK. 
8.2.1 
Biological Samples 
A volume of 40 mL whole blood will be collected at Visits 1, 3, 5, and 6 to provide 
approximately 15 mL serum intended to be used for assay development/validation, 
protocol-mandated research and for transfer of sera samples to BARDA for future use (if 
consented by participant). The protocol-specified testing will be performed at GSK and/or 
GSK designated laboratories. 
Prior to measurement of the immune response, collected blood samples will be used to enable 
the development and the validation of the assays used in this study (HI and MN). 

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8.2.2 
Laboratory Assays 
Table 4 
Laboratory Assays 
Test classification 
System 
Component 
Method 
Laboratory 
Humoral Immunity  
Serum 
Inhibiting hemagglutination titers 
(A/Astrakhan/3212/2020-like (H5N8)) 
HI 
GSK or GSK 
designated 
Lab** 
Serum 
(subset*) 
Neutralizing titers 
(A/Astrakhan/3212/2020-like (H5N8)) 
MN 
GSK or GSK 
designated 
Lab** 
Abbreviations: H5N8=Influenza A/Astrakhan/3212/2020-like; HI=hemagglutination inhibition; 
MN=microneutralization. 
* Subset for Microneutralization testing will be performed on 50% of the participants, randomly selected and 
equally distributed across the different subgroups.  
** GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. 
CLS may designate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; Sienna, 
Italy, or to a contracted external partner laboratory. 
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. 
GSK clinical laboratories have established a Quality System supported by procedures. The 
activities of GSK clinical laboratories and GSK designated labs (third parties) are audited 
regularly for quality assessment by an internal (Sponsor-dependent) but laboratory 
independent Quality Department. 

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8.2.3 
Immunological Read-Outs 
Table 5 
Immunological Read-Outs 
Blood sampling time point 
Subset name 
No. 
participants 
Component 
Components 
priority 
rank 
Type of contact 
and timepoint 
Sampling 
time point 
 
Visit 1 (Day 1) 
Pre-Vacc I 
HI 
520 
Vaccine-homologous 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
1 
Visit 1 (Day 1) 
Pre-Vacc I 
MN 
260 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
2 
Visit 3 (Day 22) 
Pre-Vacc II 
HI 
520 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
1 
Visit 3 (Day 22) 
Pre-Vacc II 
MN 
260 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
2 
Visit 5 (Day 43) 
Post-Vacc II 
HI 
520 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
1 
Visit 5 (Day 43) 
Post-Vacc II 
MN 
260 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
2 
Visit 6 (6 months 
post dose 2) 
Post-Vacc II 
HI 
520 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
1 
Visit 6 (6 months 
post dose 2) 
Post-Vacc II 
MN 
260 
Vaccine-homologous 
Influenza 
(A/Astrakhan/3212/2020- 
like (H5N8)) 
2 
Abbreviations: HI=hemagglutination inhibition; MN=microneutralization; No.=number; 
vacc=vaccine. 
8.2.4 
Immunological Correlates of Protection 
Although there is no accepted correlate of protection against influenza virus, either seasonal or 
pandemic, the protective role of antibodies against HA and, to a lesser extent, neuraminidase, 
is well established and has been demonstrated both in experimentally infected animals and 
humans.15  

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For this reason, the induction of HA-specific antibodies is used as a marker of potential 
vaccine efficacy and the serum HI assay is used to demonstrate this humoral response. 
Hemagglutination inhibition titers of 1:40 or greater have been associated with protection 
from influenza illness in at least 50% of participants in challenge studies and correlate with 
vaccine effectiveness.16,17 
8.3 
Pre- and Post- Vaccination Procedures 
8.3.1 
Check Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be re-checked as described in Sections 5.1 and 5.2 
before dosing on Visit 1 and Visit 3. 
8.3.2 
Body Temperature 
Body temperature must be assessed prior to study intervention administration and/or blood 
draw.  
If the participant has fever (fever is defined as temperature ≥38.0°C [100.4°F] regardless of 
the location of measurement) on the day of vaccination, the vaccination visit will be 
rescheduled within the allowed interval for this visit (Table 2). 
If the investigator determines that the participant’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled. 
8.3.3 
Pregnancy Testing 
Female participants of childbearing potential must perform a urine pregnancy test prior to any 
study vaccine administration. Pregnancy testing must be performed 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. 
Refer to the Section 10.6.2 for the information on study continuation for participant who 
becomes pregnant during the study. 
8.3.4 
Medical History 
Changes or updates to participant medical history since Screening Visit will be recorded in 
eCRF.  
8.3.5 
Medication and Vaccine History 
Changes or updates to participant medical history since Screening Visit will be recorded in 
eCRF.  

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8.3.6 
Post-Vaccination Observation Period 
Participants will undergo a 30-minute observation period immediately following 
administration of each dose of study vaccine, where they will be assessed by a qualified 
healthcare professional for any signs of any adverse events. 
8.4 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE, SAE, or pIMD. The investigator and any designees 
remain responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant to discontinue the study.  
8.4.1 
Safety Laboratory Assessments 
At Visits 2 and 4, a whole blood sample of approximately 6 mL will be drawn from the first 
50% of participants of each age/dose group for the following laboratory assessments: 
Hematology: complete blood count with differential and platelet count; Chemistry/metabolic 
panel: Sodium, Potassium, ALT, AST, Alkaline Phosphatase, total bilirubin, creatinine, and 
BUN. 
The post-vaccination clinical safety laboratory assessments will be performed by a central 
laboratory as detailed in the Laboratory Manual. See Section 10.3 for the FDA Toxicity 
Grading Scale. See Section 10.4 for management of participants with abnormal laboratory 
values. 
8.4.2 
Study Holding Rules and Safety Monitoring 
8.4.2.1 
Internal Safety Review Committee 
The study will also include 2 planned iSRC reviews. The iSRC reviews will occur after the 
safety data for the 7 days post dose 1of the first 50 participants have been recorded and are 
available. The second iSRC review will occur after the first 50 participants have completed 
7 days post dose 2, and the safety data is available. 
Enrollment will be capped to 20 participants per day until the iSRC reviews have been 
completed. Following iSRC recommendation, the enrollment will be opened with no 
limitations. 
8.4.2.2 
Study Holding Rules 
Holding rules in Table 6 will be assessed by each investigator on a continuous basis. Meeting 
any of these holding rules will trigger a hold of vaccination irrespective of number of 
participants enrolled and/or timing of the event. 

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Of note, no formal holding rules will be applied for other safety data. However, if available, 
these data will also be reviewed in order to allow an overall assessment of the benefit/risk 
ratio of vaccination. 
If any investigator becomes aware of a holding rule being met, he/she will suspend 
vaccination and inform the medical monitor immediately. 
Table 6 
Study Holding Rules 
Holding Rule 
Event (per dose and per individual study group) 
Number of 
Participants 
1a 
Death or any life-threatening SAE that cannot be reasonably attributed to a 
cause other than vaccination as per investigator or Sponsor assessment 
≥1 
1b 
Any non-life-threatening SAE that cannot be reasonably attributed to a cause 
other than vaccination as per investigator or Sponsor assessment 
≥1 
Abbreviations: SAE=serious adverse event. 
8.5 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.5. 
The definitions of unsolicited and solicited events can be found in Section 10.5.1. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs until the event has resolved, subsided, stabilized, disappeared, or until 
the event is otherwise explained, or the participant is lost to follow-up, irrespective of 
seriousness or relatedness (see Section 7.0). 
This includes events reported by the participant (or, when appropriate, by a caregiver, 
surrogate). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.5 and 
10.5.3. 
8.5.1 
Time Period and Frequency for Collecting AE, SAE, pIMD, MAE 
Information 
Serious AEs assessed as related to study participation (e.g., study intervention, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a 

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GSK product (non-IMP) will be recorded from the time a participant consents to participate in 
the study. 
All SAEs (not related to study participation), pIMDs, medically attended adverse events 
(MAEs), and pregnancies will be collected from the start of study intervention until 6 months 
after the last vaccination at the time points specified in the SoA (Section 1.3). 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded as medical history/current medical conditions, not as AEs. 
All SAEs and pIMDs (pIMDs can be serious or non-serious) will be recorded and reported to 
the Sponsor or designee immediately and under no circumstance should this exceed 24 hours 
of the investigator’s awareness of the event, as indicated in Section 10.5.5. The investigator 
will submit any updated SAE or pIMD data to the Sponsor or designee within 24 hours of 
their awareness of the updated information. 
All unsolicited AEs that occur within 21 days following administration of each dose of study 
intervention and MAEs that occur at any time during the study must be recorded onto the 
appropriate section of the eCRF, irrespective of their intensity or whether or not they are 
considered related to the study intervention.  
All solicited events that occur within 7 days following administration of each dose of study 
intervention must be recorded into the diary, irrespective of intensity. All other AEs occurring 
within this time frame should be recorded on the appropriate section of the eCRF, irrespective 
of their intensity or whether or not they are considered related to the study intervention.  
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion 
of the study participation. However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he/she considers the 
event/cause of death to be reasonably related to the study intervention or study participation, 
the investigator must promptly notify the Sponsor or designee. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting safety reports are provided in Sections 10.5.3 and 
10.5.5. 

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Table 7 
Timeframes for Recording and Reporting Safety Information 
Event 
Screening 
Visit 
Pre- 
Dose 
Visit 1 
Visit 2* 
or 
Remote 
Visit 
Visit 3 
Visit 4* 
or 
Remote 
Visit 
Visit 5 
Visit 6 
6 months 
post dose 2 
 
 
Day 1 
Dose 1 
Days  
8-10 
Day 22 
Dose 2 
Days  
29-31 
Day 43 
Administration site and Systemic solicited 
events 
Unsolicited AEs 
AEs/SAEs leading to withdrawal from the study 
SAEs 
 
SAEs related to the study intervention 
 
Pregnancy 
 
 
All pIMDs  
 
MAEs  
 
Abbreviations: AE=adverse event; MAE=medically attended adverse event; SAE=serious adverse event; pIMD=potential immune-mediated disease. 
* The first 50% of study participants in each age and dose group will be required to have safety laboratory assessments performed at the clinic 7-days post each 
vaccination (i.e., Visit 2 and Visit 4). All other participants will have a remote visit with the site. 

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8.5.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
Participants must be made aware of the requirement to report any new medical condition or 
worsening of any pre-existing medical condition requiring contact with a healthcare 
professional to the site staff.  
8.5.2.1 
Clinically Significant Abnormal Laboratory Findings 
Post-vaccination clinical laboratory measurements (Section 8.4.1) are scheduled for the first 
50% of participants enrolled in each age/dose group. These laboratory measurements may also 
be performed, and the results obtained as part of critical care or follow-up due to the 
occurrence of MAEs, SAEs, or pIMDs during the study. 
The investigator must review the laboratory report, document that he/she did so, and record 
any clinically relevant changes occurring during the study in the eCRF. Clinically significant 
abnormal laboratory findings are those which are associated with an underlying disease 
judged by the investigator to be more severe than expected for the participant's condition. 
These results should be reported as an AE, MAE, SAE, or Adverse Events of Special Interest 
(AESI) as applicable for the study. 
See Section 10.3 for the FDA Toxicity Grading Scale and Section 10.4 for the management of 
participants with abnormal laboratory values. 
 
8.5.3 
Treatment of Adverse Events 
Any medication administered for the treatment of an SAE/pIMD should be recorded in the 
Expedited Adverse Events report of the participant’s eCRF screen. 
8.5.4 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs (Section 10.5) will be followed until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up 
(as defined in Section 7.3). Further information on follow-up procedures is provided in 
Section 10.5. 
8.5.5 
Regulatory Reporting Requirements for SAEs and Other Events 
Prompt notification by the investigator to the Sponsor of an SAE or pIMD is essential so that 
legal obligations and ethical responsibilities toward the safety of participants and the safety of 
a study intervention under clinical investigation are met. 

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The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, IRBs/IECs, and investigators. 
For SAEs and pIMDs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.5.3. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then 
file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements. 
Table 8 
Timeframes for Submitting SAE, Pregnancy, pIMDs to IQVIA 
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡‡ 
Electronic‡ AEs 
Report 
24 hours* 
Electronic‡ AEs Report 
Pregnancies  
24 hours* 
Electronic pregnancy 
report 
24 hours * 
Electronic pregnancy 
report 
pIMDs 
(whether serious 
or non-serious) 
24 hours** ‡‡ 
Electronic‡ AEs 
Report 
24 hours* 
Electronic‡ AEs Report 
Abbreviation: AE=adverse event; SAE=serious adverse event; pIMD=potential immune-mediated disease. 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡ Paper AEs report may be submitted in the case that the electronic system is not functioning. The paper report 
will be dated and signed by the investigator (or designee). 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. 
‡‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box 
in the electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD. 
 
8.5.6 
Pregnancy 
Details of all pregnancies in study participants will be collected after the start of study 
intervention and until the outcome of the pregnancy is known. Female participants who 
become pregnant after the first study intervention dose must not receive the second dose of the 
study intervention but may continue other study procedures at the discretion of the 
investigator. 

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If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor or designee within 24 hours of learning of the 
participant’s pregnancy and should follow the procedures outlined in Section 10.5.3 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including if found in 
an aborted fetus, stillbirth, or neonatal death]) the investigator will report according to the 
SAE reporting procedures described in Section 10.5.5. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will 
be forwarded to the Sponsor or designee. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the Sponsor as described in Section 8.5.5. While the 
investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
8.5.7 
Adverse Events of Special Interest 
8.5.7.1 
Potential Immune-Mediated Diseases 
Potential immune-mediated diseases 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. Adverse events that need to be recorded and reported as pIMDs include 
those listed in Table 16 and must be reported in an expedited manner regardless of causality, 
seriousness, or medical opinion on etiology.  
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 as a new onset condition (if it started following 
vaccination) in the eCRF. 

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8.5.8 
Participant Card 
The investigator (or designee) must provide the participant/participant’s caregiver(s) with a 
“participant card” containing information about the clinical study. The 
participant/participant’s caregiver(s) must be instructed to always keep the participant card in 
their possession for the duration of the study. In an emergency, this card serves to inform the 
responsible attending physician/caregiver/family member that the participant is in a clinical 
study and that relevant information may be obtained by contacting the investigator(s) or their 
back-up. 
8.6 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.7 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.8 
Genetics 
Genetics are not evaluated in this study. 
8.9 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.10 Immunogenicity Assessments 
Immunogenicity Assessments are described in Section 8.2. 
8.11 Health Economics 
Health economics parameters are not evaluated in this study. 
 

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9.0 STATISTICAL CONSIDERATIONS 
The Statistical Analysis Plan (SAP) will be finalized prior to first subject first visit (FSFV). 
9.1 
Statistical Hypotheses 
The null hypotheses for vaccine-homologous HI titer at Day 43 in 18 to 64 years age or in 
65 years of age or above) are: 
for 18 to 64 years of age: H01: seroprotection rate (SPR) < 70%  
for 65 years of age or above: H02: SPR < 60%  
Null hypotheses will be assessed according to a hierarchical order of study groups as given 
below.  
1. 7.5 mcg antigen + AS03A 
2. 7.5 mcg antigen + AS03B 
3. 3.75 mcg antigen + AS03A 
4. 3.75 mcg antigen + AS03B 
No multiplicity adjustment is required as the hypothesis for each study group will be tested if 
the success criteria will be met for the previous group in the hierarchy. Accordingly, a 
nominal type I error of 2.5% will be used for each dose group and the objective will be met 
for one dose group if all 2 null hypotheses are rejected simultaneously. 
Criteria for success to be met simultaneously for a study group: 
• The lower limit (LL) of the 95% confidence interval (CI) for the SPR meets or exceeds 
70% for adults of 18 to 64 years of age. 
• The LL of the 95% CI for the SPR meets or exceeds 60% for adults ≥65 years of age. 
9.2 
Sample Size Determination 
A total of 520 participants are planned to be enrolled, with 65 participants per age subgroup in 
each of the 4 dose groups. 
A non-evaluable rate of  23% and 30% in 18 to 64 years of age and ≥65 years of age groups, 
respectively yield an approximate sample size of 95 evaluable participants per dose group 
(i.e., 50 participants between 18 to 64 years of age and 45 participants above 65 years of age 
in each dose group), giving 77.8% overall power to fulfill the 2 SPR immunogenicity criteria 
in any in the first group that is 7.5 mcg antigen + AS03A. This assumes that the SPR are truly 
20% higher than the critical value (namely 90% for participants 18 to 64 years of age and 80% 
for participants ≥65 years of age, respectively). 

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The statistical power in 7.5 mcg antigen + AS03A group will be 91.4% if the SPR is assumed 
as 85% in ≥65 years of age. 
9.3 
Analysis Sets 
Table 9 
Analysis Sets 
Analysis Set 
Description 
Analyses 
Evaluated 
Screened 
All participants who were screened for eligibility. 
Study Population 
Enrolled (ENR) 
All participants who were randomized, received 
study intervention or had immunogenicity blood 
sample. 
Study Population 
Exposed Set (ES) 
Participants who received a study intervention. 
Participants will be analyzed according to the 
study intervention administered at dose 1. 
Safety (unsolicited 
AE, number of 
participants with 
changes in 
laboratory toxicity 
grading from 
baseline, SAE, 
pIMD, MAE) 
Diary Set (DS) 
Participants who received a study intervention and 
provided information on solicited AEs. 
Participants will be analyzed according to the 
study intervention administered at dose 1. 
Solicited AE 
Per Protocol Set (PPS) 
All eligible participants who received the 2 doses 
of study intervention as per protocol, had Day 1 
and Day 43 post dose anti-HI immunogenicity 
results as per blood draw interval at Day 43. 
In addition, participant data at a specific blood 
draw visit will be excluded from the PPS when: 
• 
Results from a serological blood sample 
deviated from blood draw intervals (refer 
to Table 2) 
• 
Results from a serological blood sample 
occurred after intercurrent conditions that 
may interfere with immunogenicity (i.e., 
immunosuppressive, immunodeficient 
conditions, or malignancy) or after a 
prohibited concomitant 
medication/vaccination  
The analysis will be done according to the 
treatment that participants received at Visit 1. 
Efficacy 
The PPS will be 
used for the 
immunogenicity 
analyses. 
 

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9.3.1 
Criteria for Elimination from Analysis 
All conditions leading to full or partial data elimination of a participant for the per protocol set 
(PPS) analysis will be classified as major protocol deviations. These conditions are already 
mentioned in the PPS definition and will be further detailed in the SAP and the Study 
Deviation Rules document which will be finalized prior to the interim analysis defined in 
Section 9.5. 
Key major deviations include, but are not limited to, the following:  
• Participants enrolled who did not meet eligibility criteria 
• Participants incorrectly vaccinated 
• Participants who did not receive study vaccinations as planned in protocol 
• Participants who did not have serological blood draws as planned in protocol 
• Participants with a blood draw outside of allowed time window 
• Participants with a vaccination done outside of allowed time window. These key major 
deviations will be assessed based on the data collected in the eCRFs. 
• Occurrence of immunosuppressive or immunodeficient conditions before a blood draw 
visit. 
9.4 
Statistical Analyses 
The SAP will be developed and finalized before FSFV and will include a more technical and 
detailed description of the statistical analyses including the supportive analyses and 
demographic summaries. This section is a summary of the planned statistical analyses of the 
primary and secondary endpoints. 
9.4.1 
General Considerations 
All analyses will be provided separately for each age subgroup. 
Derived and transformed data: 
• Immunogenicity at a visit (Note: The lower limit of quantitation (LLOQ) is defined by the 
laboratory before the analysis and will be specified in the clinical study report). 
o A seronegative participant is a participant whose titer is below the LLOQ. 
o A seropositive participant is a participant whose titer is greater than or equal to the 
LLOQ. 
o Seroprotection is defined as an HI titer ≥1:40. 
o SPR is defined as the percentage of participants with an HI titer ≥1:40. 
o HI seroconversion is defined as a post-vaccination titer ≥1:40 in the serum of 
participants with pre-vaccination titer below 1:10 or as a ≥4-fold rise in 
post-vaccination HI titer with pre-vaccination titer ≥1:10. 

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o SCR is defined as the percentage of participants who seroconvert post-vaccination. 
o MN vaccine response (VR) is defined as titer ≥4× LLOQ for participants with 
pre-vaccination titer below LLOQ or as a ≥4-fold increase in MN titer for 
participants with pre-vaccination titer ≥LLOQ.  
o Vaccine response rate (VRR) is defined as the percentage of participants with 
vaccine response. 
o Geometric Mean Titer (GMT) calculations are performed by taking the anti-log of 
the mean of the log concentration/titer transformations. Values for the 
concentrations/titers below the LLOQ will be assigned half the LLOQ for the 
purpose of GMT computation. 
o Handling of missing data: for a given participant and a given immunogenicity 
measurement, missing or non-evaluable measurements will not be replaced. 
o The primary and secondary HI immunogenicity analyses will be based on the PPS. 
o The MN immunogenicity analyses will be based on the PPS. 
• Reactogenicity and Safety − Handling of missing data: For safety analyses, participants 
who missed reporting symptoms (solicited or unsolicited) or concomitant medications will 
not be imputed. Therefore, the analysis of the solicited symptoms based on the DS will 
include only participants/doses with documented safety data (i.e., symptom screen/sheet 
completed). Further details on the handling of missing data will be described in the SAP. 
9.4.2 
Participants Disposition 
Participant disposition will be summarized for the enrolled set across groups and for ES for 
each study group and overall. The summary will include the number of participants in each 
analysis set defined in Section 9.3, the number and percentage of participants who received 
any and each study vaccination, the number and percentage of participants who completed the 
study and/or the primary reason for withdrawal from the study, the number and percentage of 
participants who completed the study vaccinations and/or the primary reason for withdrawal 
of study vaccination.  
The number and percentage of participants who were screen failures and the major reason for 
screen failure will be summarized for the Screened set as overall.  
Major deviations will be summarized for the ES for each study group and overall.  
The reason for elimination from the DS and from the PPS will also be summarized at each 
vaccination and post-vaccination blood draw respectively.  
Listings will be provided for disposition data and deviation data based on the enrolled set. 

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9.4.3 
Primary Endpoint(s)/Estimand(s) Analysis 
9.4.3.1 
Immunogenicity 
Primary immunogenicity analyses will be based on the PPS. 
GMTs and associated 95% CI will be calculated for each study group for vaccine-homologous 
H5N8 HI titer at Day 43. 
GMFR increase at Day 43, compared to pre-vaccination and associated 95% CI will be 
calculated for each study group for vaccine-homologous H5N8 HI titer at Day 43. The GMT 
and GMFR CIs will be derived from an Analysis of Covariance (ANCOVA) model on 
log-transformed titer. The model will include the dose group effect (i.e., 4 dose groups), as a 
fixed effect and the log-transformed titer pre-dose 1 (Day 1) as a covariable. 
SPR at Day 43 will be calculated for each study group for vaccine-homologous H5N8 HI titer 
along with Clopper-Pearson exact two-sided 98.75% CIs. 
9.4.3.2 
Safety 
The analysis of reactogenicity will be based on the DS while the analysis of other safety 
endpoints such as unsolicited events will be based on the ES. The following analysis will be 
generated for each vaccine group. 
Solicited administration site and systemic endpoints 
The following summaries will be generated for any grade (Table 13), grade ≥2, grade ≥3, 
medically attended, ongoing after day 7:  
• Occurrence of at least one solicited administration site event during a 7-day follow-up 
period (i.e., day of vaccination and 6 subsequent days) after each vaccination and overall.  
• Occurrence of at least one solicited systemic event during a 7-day follow-up period (i.e., 
day of vaccination and 6 subsequent days) after each vaccination and overall.  
• Duration of each solicited AE starting on the day of vaccination or on one of the 
6 subsequent days will be summarized after each vaccination and overall. 
Frequencies and percentages of participants experiencing each event will be presented for 
each vaccination and across vaccinations with Clopper-Pearson exact 95% CIs. 
If a solicited event occurs more than once for a participant, it will be counted in the summary 
only once for each level of summarization, according to the maximal severity.  
Laboratory endpoints 
The percentage of participants with an increase in laboratory toxicity grading after each 
vaccination and across vaccinations will be provided with Clopper-Pearson exact 95% CIs. 

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This will be done for each safety laboratory test and across laboratory tests for exposed 
participants with safety laboratory results available after vaccination.  
Unsolicited AE and MAE endpoints 
• Occurrence of unsolicited AEs within 21 days (day of vaccination and 20 subsequent 
days) after each vaccination and overall. 
• Occurrence of MAEs within 21 days (day of vaccination and 20 subsequent days) after 
each vaccination and also through 6 months post dose 2. 
SAE/pIMD endpoints 
• Occurrence of SAEs and pIMDs up to Visit 5 (Day 43) and also through 6 months post 
dose 2. 
The original verbatim terms used by investigators to identify AEs in the eCRFs will be 
mapped to preferred terms (PTs) using the Medical Dictionary for Regulatory Activities 
(MedDRA). The AEs will then be grouped by Medical Dictionary for Regulatory Activities 
PTs into frequency tables according to system organ class.  
For each of the unsolicited AE, SAE, and pIMD endpoints the number of participants and 
percentage will be summarized regardless of MedDRA classification and by system organ 
class and by preferred term within system organ class for each study group.  
Separate summaries will be produced for the following categories: 
• AE of any grade 
• AEs of any grade that are possibly or probably related to vaccine(s) 
• Grade 3 AE 
• Grade 3 AE that are possibly or probably related to vaccine(s) 
• MAE of any grade 
• pIMDs 
• SAEs 
• SAEs related to vaccine 
• Fatal SAE 
• Fatal SAE related to vaccine 
Data listings of all AEs will be provided by participant. In addition, AEs in the categories 
above will be provided as listed data. 

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9.4.4 
Secondary Endpoint(s) Analysis 
9.4.4.1 
Immunogenicity  
Secondary immunogenicity analyses will be based on the PPS. 
Geometric mean titers with associated 95% CI will be calculated for each study group for 
vaccine-homologous H5N8 HI titer at Days 1, 22, and 6 months post dose 2. Geometric mean 
fold rise increase compared to pre-vaccination and associated 95% CI will be calculated at 
Days 22, and 6 months for each study group for vaccine-homologous H5N8 HI antibody titer. 
The GMT and GMFR CIs will be derived from an ANCOVA model on log-transformed titer. 
The model will include the dose group effect (i.e., 4 dose groups), as a fixed effect and the 
log -transformed titer pre-dose 1 (Day 1) as a covariable. 
The following aggregate variables will be calculated for each study group for 
vaccine-homologous H5N8 HI antibody titer along with Clopper-Pearson exact two-sided 
95% CIs: 
• SCR at Day 22, Day 43, and 6 months post dose 2, and 
• SPR at Day 1, 22, and 6 months post dose 2. 
For a subset of participants with Microneutralization (MN) antibody titers, the following 
aggregate variables will be calculated for each study group for vaccine-homologous H5N8 
MN antibody titer: 
• GMTs at Days 1, 22, 43, and 6 months post dose 2 
• Seropositivity rates at Days 1, 22, 43, and 6 months post dose 2 
• VRR at Days 22, 43, and 6 months post dose 2 
The GMTs with 95% CIs will be tabulated by visit for each study group. For 
seropositivity/VRR, percentage of participants will be calculated with Clopper-Pearson exact 
two-sided 95% CIs. 
9.4.5 
Demography and Baseline Characteristic Analyses 
Demographic characteristics (age, gender, race, center, country, ethnicity, and occupation) 
will be tabulated per study group for ES and PPS, as described in the SAP.  
For continuous characteristics, mean, range, and standard deviation will be calculated.  
For discrete variables, distribution, and associate frequency will be calculated.  
Listings will be provided for demographic characteristic data based on the enrolled set.  

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9.5 
Interim Analysis 
An interim analysis will be performed on data collected through the Day 43 visit. This interim 
analysis will provide treatment-level unblinded summaries for GSK, and BARDA, and no 
individual unblinding data will be provided. The details of the interim analysis are provided in 
Section 9.5.1 and will be fully detailed in the SAP. 
9.5.1 
Sequence of Analyses 
9.5.1.1 
Interim Safety Analysis at Day 43 
An analysis will be performed on data collected through the Day 43 visit. Elements will 
include: 
• Analyses of cleaned solicited administration site events and solicited systemic events 
data collected during a 7-day follow-up period (i.e., day of vaccination and 
6 subsequent days) after each vaccination. 
• Analyses of unsolicited AEs reported up to the Day 43 visit (i.e., day of vaccination 
and 20 subsequent days after each vaccine) and cleaned in so far as is possible. 
• Analyses of SAEs, pIMDs, MAEs, pregnancies, and withdrawals due to AEs, collected 
up to the Day 43 visit. 
• No study report will be prepared. Access to individual treatment codes will be 
restricted to the designated statisticians in charge of the analysis. No individual listings 
or data with the participants’ identifying information will be disseminated. Listings of 
final data will be provided with the EOS report. 
9.5.1.2 
Interim Immunogenicity Analysis at Day 43 
An analysis will be performed on data collected through the Day 43 visit. Elements will 
include: 
• Analyses of cleaned immunogenicity data, for analysis of vaccine-homologous HI 
antibody titers and MN titers, collected through the Day 43 visit. 
• Results will be presented in a Day 43 statistical report. Access to individual treatment 
codes will be restricted to the designated statisticians in charge of the analysis. No 
individual listings or data with the participants’ identifying information will be 
disseminated. Listings of final data will be provided with the EOS report. 
All analyses will be performed on data that has been cleaned and locked. The possibility of 
post-analysis changes to data evaluated at Day 43 exists, since data collection and data entry 

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may continue through 6 months post dose 2. All final data will be presented in the listings 
provided at 6 months post dose 2. 
9.5.1.3 
Final Analysis (6 Months Post Dose 2) 
A final data analysis will be performed at the EOS (6 months post dose 2) of all primary and 
secondary endpoints based on the clean data, including evaluations of: 
• Immunogenicity at all measured time points. 
• Solicited administration site events and solicited systemic events data reported within 
7 days after each vaccination (day of vaccination and 6 subsequent days following each 
vaccination). 
• Unsolicited AEs reported up to the Day 43 visit (day of vaccination and 
20 subsequent days after each vaccination). 
• Concomitant medications reported up to the Day 43 visit. 
• SAEs, pIMDs, MAEs, and withdrawals due to AEs collected throughout the entire study. 
• Pregnancies throughout the entire study. An integrated clinical study report containing all 
data will be written and made available to the investigators. 
9.5.2 
Statistical Consideration for Interim Analysis 
Since the primary endpoints for the study will be complete by the Day 43 visit (collection past 
Day 43 includes only assessments for SAEs, pIMDs, MAEs, and immunogenicity at 6 months 
post dose 2), no statistical consideration for multiplicity will be given to account for changes 
in the results reported at the interim analysis compared to the final analysis. For the primary 
immunogenicity analysis, which will be reported at Day 43 the overall type I error rate is fixed 
at 2.5% and a Bonferroni adjustment will be applied to allow simultaneous multiple 
comparisons of each antigen/adjuvant group leading to 0.625% nominal type I error. For the 
primary safety analyses no adjustment for multiple comparisons will be made in each 
antigen/adjuvant group. 
9.6 
Data Monitoring Committee 
Not applicable. 

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

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10.1.2 
Adequate Resources 
The investigator is responsible for supervising any individual or party to whom the 
investigator delegates study-related duties and functions conducted at the study site. 
If the investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the investigator/institution should ensure this individual or 
party is qualified to perform those study-related duties and functions and should implement 
procedures to ensure the integrity of the study-related duties and functions performed and any 
data generated. 
10.1.3 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.4 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant or participant’s caregiver(s) and answer all questions 
regarding the study. 
Potential participants must be informed that their participation is voluntary. Participants or 
participant’s caregiver(s) will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy, and data protection 
requirements, where applicable, and the IRB/IEC or study site. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant or caregiver(s). 
10.1.5 
Recruitment Strategy 
Poultry workers are at increased risk of avian influenza. It is intended to recruit from this 
population. 

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10.1.6 
Data Protection 
• Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
• The participant must be informed that his/her personal study -related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must also 
be explained to the participant who will be required to give consent for their data to be 
used as described in the informed consent. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
• The contract between Sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches, and respective 
communication and co-operation of the parties. 
• Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. GSK 
and/or trusted third parties working on behalf of GSK and/or institutions working with 
GSK for the purposes of this study are contractually bound to protect participant coded 
data. GSK will protect participant coded data and will only share it as described in the 
ICF. 
10.1.7 
Committees Structure 
An iSRC will be in place for this study. This is a review body internal to GSK but external to 
the vaccine project who will review unblinded data at the planned safety reviews of the first 
50 participants upon reaching 7 days post dose 1 and also upon reaching 7 days post dose 2. 
Enrollment will be capped to 20 participants per day until the iSRC reviews have been 
completed. Following iSRC recommendation, the enrollment will be opened with no 
limitations. If a pausing/holding rule (Section 8.4) is met, this will trigger a hold of 
vaccination and a review. A decision will be made, based on the review, as to whether 
enrollment in the study will be allowed to resume. 
A SRT is in place for each GSK product. It comprises of a global cross-functional team 
responsible for the ongoing assessment of benefit-risk for a product. The SRT contribute to 
the continual assessment of incoming new efficacy and safety information.  
 

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10.1.8 
Dissemination of Clinical Study Data 
The key design elements of this protocol and results summaries will be posted on 
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 reasonable access to statistical 
tables, figures, and relevant reports. GSK will also provide the investigator with the full 
summary of the study results, including a summary of trial results understandable to 
laypersons. The investigator is encouraged to share the plain language summary with the 
study participants, as appropriate. The full study report will be made available upon request, 
after the decision on marketing authorization by regulatory authorities. 
GSK will provide the investigator with the randomization codes and participant-level line 
listings for their site only after completion of the full statistical analysis. 
GSK intends to make anonymized participant-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. 
10.1.9 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or eCRFs 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 case report form (CRF). 
• Guidance on completion of eCRFs will be provided in eCRF completion guidelines. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Quality tolerance limits will be predefined in the Project Management Plan to identify 
systematic issues that can impact participant safety and/or reliability of study results. 
These predefined parameters will be monitored during the study, and important deviations 
from the quality tolerance limits and remedial actions taken will be summarized in the 
clinical study report. 

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• Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management 
and mitigation strategies and analytical risk-based monitoring), methods, responsibilities, 
and requirements, including handling of non-compliance issues and monitoring techniques 
(central, remote, or on-site monitoring) are provided in the monitoring plan. 
• The Sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 15 years from the final clinical study report or 
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. 
10.1.10 
Source Documents 
The investigator/institution should maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study site’s participants. 
Source data should be attributable, legible, contemporaneous, original, accurate, and 
complete. Changes to source data should be traceable, should not obscure the original entry, 
and should be explained if necessary (e.g., via an audit trail). 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in Monitoring 
Management Plan.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized study site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 

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being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.11 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first study site open. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 
For study termination: 
• Discontinuation of further study intervention development. 
For study site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the investigator 
• Total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The investigator shall promptly inform the participant 
and should assure appropriate participant therapy and/or follow-up. 

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10.1.12 
Publication Policy 
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The Sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and as 
per the Sponsor’s internal policy. Authorship will be determined by mutual agreement and in 
line with International Committee of Medical Journal Editors (ICMJE) authorship 
requirements. 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before 
submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multi-center studies only in their entirety and not as individual study site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
Where required by regulation, the names of the sponsor signatory and investigator signatory 
will be made public. 
GSK intends to make anonymized participant-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. Data will be shared 
with researchers in a non-identifying way, and appropriate measures will be taken to protect 
PI; these measures will comply with data protection and privacy laws that apply. 
 
 

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10.2 Appendix 2: Clinical Laboratory Tests 
Hemagglutination Inhibition Assay 
Hemagglutination inhibition titers are determined using the method derived from the WHO 
Manual on Animal Influenza Diagnosis and Surveillance, WHO/CDS/CSR/NCS/2002.5. 
Measurements are conducted on thawed frozen serum samples with a standardized and 
comprehensively validated micromethod. The standard operating procedure describes a HI test 
for detecting H5N8 influenza A specific responses, such as those following influenza virus 
vaccinations. Briefly, serum samples are first adsorbed with RBCs to remove non-specific 
agglutinins and then treated with receptor destroying enzyme overnight to remove 
non-specific inhibitors of the hemagglutination, then diluted to 1:10, and serial diluted 2-fold 
in duplicate from 1:10 to 1:10240. After addition of an equal volume of standardized virus 
(4 HAU/25 μL), antibodies that inhibit virus-mediated hemagglutination react with the virus 
for 1 hour at room temperature, and then horse red blood cells (RBCs) are added to the 
mixture. Plates are tilted and the titer is the reciprocal of the last dilution that fully inhibits 
hemagglutination as compared to a red blood cell control well. Each serum sample will be 
tested in duplicate within the same assay. The final result corresponds to the GMT for the 
duplicate. 
Microneutralization Assay 
Microneutralization titers are determined using the method derived from the WHO Manual for 
the laboratory diagnosis and virological surveillance of influenza.21 
Measurements are conducted on thawed frozen serum samples. Samples are heat-inactivated 
at 56°C. A standardized amount of virus is mixed with serial dilutions of serum and incubated 
at 37°C to allow binding of the antibodies to the virus. A cell suspension containing a defined 
amount of Madin-Darby Canine Kidney cells is then added to the mixture of virus and 
antiserum and incubated at 37°C. After overnight incubation, plates are fixed and the amount 
of virus per well is detected by enzyme-linked immunosorbent assay using anti-nucleoprotein 
monoclonal antibodies. The virus neutralizing titer is determined using a formula that 
calculates the midpoint optical density of uninfected cells and virus infected (without 
neutralization) cells. 

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10.3 Appendix 3: FDA Toxicity Grading Scale 
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate.22 

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Table 10 
Table of Laboratory Abnormalities 
Serum * 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening  
(Grade 4)** 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125 
Sodium – Hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
> 150 
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
> 5.6 
Potassium – Hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
< 3.1 
BUN mg/dL 
23 – 26 
27 – 31 
> 31 
Requires 
dialysis 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires dialysis 
Alkaline phosphate – 
increase by factor 
1.1 – 2.0 x ULN 
2.1 – 3.0 x ULN 
3.1 – 10 x ULN 
> 10 x ULN 
Liver Function Tests –ALT, AST 
increase by factor 
1.1 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10 x ULN 
> 10 x ULN 
Bilirubin – when accompanied 
by any increase in Liver Function Test increase by 
factor 
1.1 – 1.25 x ULN 
1.26 – 1.5 x ULN 
1.51 – 1.75 x ULN 
> 1.75 x ULN 
Bilirubin – when Liver Function Test 
is normal; increase by factor 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.0 – 3.0 x ULN 
> 3.0 x ULN 
Hemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (Female) 
change from baseline value - gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (Male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (Male) 
change from baseline value – gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 

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Serum * 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening  
(Grade 4)** 
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 
Lymphocytes Decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - cell/mm3 
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate transaminase; BUN=blood urea nitrogen; ULN=upper limit of normal; WBC=white blood cell. 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal parameters. Institutional normal reference ranges 
should be provided to demonstrate that they are appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the laboratory abnormalities as Potentially Life 
Threatening (Grade 4). For example. a low sodium value that falls within a Grade 3 parameter (125-129 mE/L) should be recorded as a Grade 4 hyponatremia 
event if the subject had a new seizure associated with the low sodium value. 
Source: Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.22 
 

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10.4 Appendix 4: Management of Participants with Abnormal Laboratory 
Values 
 
Figure 2 
Screening and Safety Laboratory Schema 
 

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10.5 Appendix 5: AEs, SAEs, and pIMDs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention 
10.5.1 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study intervention, whether or not considered related to the study 
intervention. 
NOTE: 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 study intervention. 
 
Definition of Unsolicited AEs, MAEs, and Solicited Events 
• 
An unsolicited AE is an AE that was not otherwise solicited in a participant diary and that is 
communicated by a participant/participant’s caregiver(s) who has signed the informed 
consent. Unsolicited AEs include serious and non-serious AEs. 
• 
An unsolicited AE is an AE that was either not included in the list of solicited events or 
could be included in the list of solicited events but with an onset outside the specified period 
of follow-up for solicited events. Unsolicited AEs must have been communicated by 
[participants/ participant’s caregiver(s)] 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, emergency room visit, or visit to/by a healthcare provider). The 
participant/participant’s caregiver(s) will be instructed to contact the study site as soon as 
possible to report MAEs, as well as any events that, though not medically attended, are of 
participant/participant’s caregiver(s) concern. Detailed information about reported 
unsolicited AEs will be collected by qualified study site personnel and documented in the 
participant’s records. 
• 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant/participant’s caregiver(s) will be collected during an interview with the 
participant/participant’s caregiver(s) and by review of available medical records at the next 
visit. 
• 
Solicited events are predefined administration site and systemic events for which the 
participant is specifically questioned, and which are noted by the participant in their diary. 
• 
Solicited Administration Site Events 
Table 11 
Solicited Administration Site Events 
All Age Subgroups 
Pain 

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Redness 
Swelling 
 
• 
Solicited Systemic Events 
Table 12 
Solicited Systemic Events 
All Age Subgroups 
Fatigue 
Fever 
Headache 
Muscle Ache  
Joint pain 
Shivering (Chills) 
Sweating 
Gastrointestinal 
symptoms: 
Nausea 
Vomiting 
Diarrhea 
Abdominal pain 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• 
New condition detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention-intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming intent. 
Such overdoses should be reported regardless of sequelae. 

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• 
Significant failure of an expected pharmacologic or biological action. 
• 
Events that occur as a result of protocol-mandated procedures (i.e., invasive procedures, 
modification of participant’s previous therapeutic regimen). 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
that are associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• 
An elective surgery/procedure scheduled to occur during a study will not be considered an 
AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry. However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure is 
being done will be considered an AE.  
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital, admission for routine examination.). 
• 
Anticipated day-to-day- fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. Pre-existing diseases 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. 
10.5.2 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more 
of the criteria listed: 
a. Results in death 
• 
For SAEs with the outcome of death, the date and cause of death will be recorded on the 
appropriate CRF. 
b. Is life-threatening 
• 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted (usually involving at 
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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. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• 
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, and accidental trauma 
(e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
• 
The term congenital anomaly/birth defect means there is suspect that exposure to a medical 
product prior to conception or during pregnancy may have resulted in an adverse outcome in 
the child. 
f. Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy). 
g. Is a suspected transmission of any infectious agent via an authorized medicinal product. 
h. Other situations: 
• 
Medical or scientific judgment should be exercised by the investigator in deciding whether 
SAE reporting is appropriate in other situations such as significant medical events that may 
jeopardize the participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These events should usually be considered 
serious. 
o 
Examples of such events include invasive or malignant cancers, intensive treatment for 
allergic bronchospasm, blood dyscrasias, convulsions or development of intervention 
dependency or intervention abuse. 
10.5.3 
Recording and Follow-Up of AE, SAE, and/or pIMD 
AE, SAE, and pIMD Recording 
• 
When an AE/SAE/pIMD occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE/pIMD information in the eCRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor or designee in lieu of completion of the applicable/required report 
form. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor or designee. In this case, all participant identifiers, with the exception of the 

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participant number, will be redacted on the copies of the medical records before submission to 
the Sponsor or designee. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
10.5.3.1 
Assessment of Intensity and Causality 
Assessment of Intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 13 
Intensity Scales for Solicited Events in Adults 18 Years of Age or Older 
Adults (18 years) 
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. 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated. 
 
2 
Moderate: Headache that interferes with normal 
activity. 
 
3 
Severe: Headache that prevents normal activity. 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated. 
 
2 
Moderate: Fatigue that interferes with normal 
activity. 
 
3 
Severe: Fatigue that prevents normal activity. 
Muscle ache all over body 
0 
Normal 
 
1 
Mild: Muscle aches that are easily tolerated. 
 
2 
Moderate: Muscle aches that interfere with normal 
activity. 
 
3 
Severe: Muscle aches that prevent normal activity. 
Joint pain 
0 
Normal 
 
1 
Mild: Joint pain that is easily tolerated. 
 
2 
Moderate: Joint pain that interferes with normal 
activity. 

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3 
Severe: Joint pain that prevents normal activity. 
Shivering (chills) 
0 
Normal 
 
1 
Mild: Shivering (chills) that is easily tolerated. 
 
2 
Moderate: Shivering (chills) that interferes with 
normal activity. 
 
3 
Severe: Shivering (chills) that prevents normal 
activity. 
Sweating 
0 
Normal 
 
1 
Mild: Sweating that is easily tolerated. 
 
2 
Moderate: Sweating that interferes with normal 
activity. 
 
3 
Severe: Sweating that prevents normal activity. 
Gastrointestinal symptoms: 
nausea, vomiting, diarrhea 
and/or abdominal pain 
0 
Normal 
 
1 
Mild: Gastrointestinal symptoms that are easily 
tolerated. 
 
2 
Moderate: Gastrointestinal symptoms that interfere 
with normal activity. 
 
3 
Severe: Gastrointestinal symptoms that prevent 
normal activity. 
Redness at administration site 
Record greatest surface diameter in mm 
Swelling at administration site 
Record greatest surface diameter in mm 
Temperature 
 
Record temperature in °C/°F. Oral route is preferred. 
 
The maximum intensity of local injection site redness/swelling will be scored as follows: 
0: 
≤20 mm 
1: 
>20 to 50 mm 
2: 
>50 to 100 mm 
3: 
>100 mm 
The maximum intensity of fever will be scored as follows: 
0: 
<38.0°C (<100.4°F) 
1: 
≥38.0 – 38.4°C (≥100.4 – 101.2°F) 
2: 
≥38.5 – 38.9°C (≥101.3 – 102.1°F) 
3: 
≥39.0 – 40.0°C (≥102.2 – 104.0°F) 
4: 
>40.0°C (>104.0°F) 
The investigator will assess the maximum intensity that occurred over the duration of the event for 
all unsolicited AEs (including SAEs) recorded during the study. The assessment will be based on 

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the investigator’s clinical judgement. 
The following definitions are to be used to rate the severity of an AE: 
• 
Mild: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of daily 
living. 
• 
Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort but 
poses no significant or permanent risk of harm to the research participant. 
• 
Severe: A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 is a 
category used for rating the intensity of an event; and both AEs and SAEs can be assessed as 
Grade 3. An event is defined as ‘serious’ when it meets 1 of the predefined outcomes as described 
in the Section 10.5.2. 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE/pIMD. The investigator will use clinical judgment to determine 
the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. 
• 
For causality assessments, events assessed as having a reasonable possibility of being related 
to study intervention will be considered "related." Events assessed as having no reasonable 
possibility of being related to study intervention will be considered "unrelated." 
• 
The investigator will also consult the IB and/or product information, for marketed products, in 
his/her assessment. 
• 
For each AE/SAE/pIMD, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE/pIMD and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor or designee. However, it is very 
important that the investigator always makes an assessment of causality for every event before 
the initial transmission of the SAE data to the Sponsor or designee. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 

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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 
vaccine/product? 
YES 
: 
There is a reasonable possibility that the study vaccine/product contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine/product. There are other, more likely 
causes and administration of the study vaccine/product is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 10.5.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible contributing 
factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Erroneous administration. 
• 
Other cause (specify). 
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). 
 
Follow-up of AEs, SAEs, or pIMDs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor or 
designee to elucidate the nature and/or causality of the AE, SAE, or pIMD as fully as possible. 
This may include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide the Sponsor or designee with a copy of any postmortem findings 
including histopathology. 

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• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE and/or pIMD data to the Sponsor or designee 
within 24 hours of the investigator’s awareness of the information. 
• 
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 AEs will be 
followed until the event is resolved, subsided, stabilized, disappeared, otherwise explained, or 
the participant is lost to follow-up, irrespective of seriousness or relatedness. 
Follow-up during the study 
• 
AEs/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 resolved, subsided, 
stabilized, disappeared, otherwise explained, or the participant is lost to follow-up. 
• 
If a participant dies during their participation in the study or during a recognized follow-up 
period, GSK will be provided with any available postmortem findings, including 
histopathology. 
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 AE 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 10.5.4. 
10.5.4 
Updating of SAE, pIMD, and Pregnancy Information after Removal of Write 
Access to the Participant’s eCRF 
Updating SAEs, pIMDs, and/or pregnancies after removal of write access to 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 sent to the Sponsor or designee.  
 
10.5.5 
Reporting of SAEs 
SAE Reporting to the Sponsor or Designee via an Electronic Data Collection System 
• 
The primary mechanism for reporting an SAE to the Sponsor or designee will be the 
electronic data collection system. The study site will enter the event into the electronic data 
collection system within 24 hours of the investigator’s awareness of the event. 

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• 
If the electronic system is unavailable, then the study site will use the paper SAE report form 
(see next section) to report the event and will enter the event into the electronic data 
collection system as soon as the system becomes available. 
• 
After the study is completed at a given study site, the electronic data collection system will be 
taken offline to prevent the entry of new data or changes to existing data. 
• 
If a study site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection system has been taken 
offline, then the study site can report this information on a paper SAE report form (see next 
section) to the Sponsor or designee. 
• 
If the site during the course of the study or post-study becomes aware of any serious, 
non-serious AEs, pregnancy exposure, related to any GSK non-IMP they will report these 
events to GSK or to the concerned competent authority via the national spontaneous reporting 
system. These will be classified as spontaneous individual case safety reports. 
• 
Contacts for SAE reporting can be found in study materials. 
 
SAE Reporting to the Sponsor or Designee via Paper SAE Report Form 
• 
The back-up mechanism for reporting an SAE to the Sponsor or designee will be the paper 
SAE report form. The study site will submit the SAE report form, via email, within 24 hours 
of the investigator’s awareness of the event. Facsimile transmission may be utilized as an 
alternative mode of submission, if necessary. 
• 
Notification of SAE information via telephone does not replace the need for the investigator 
to complete, sign and submit the paper SAE report form to the Sponsor or designee within 
24 hours of the investigator’s awareness of the event. 
• 
Contacts for SAE reporting can be found in study materials. 
 
 

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10.6 Appendix 6: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information 
10.6.1 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the Following Categories Are Not Considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
For permanently sterile individuals due to an alternate medical cause other than the above, 
(e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator discretion 
should be applied to determining study entry. If reproductive status is questionable, additional 
evaluation should be considered. 
NOTE: Documentation can come from the study site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.  
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
10.6.2 
Contraception Guidance 
Female Participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. Female participants of childbearing potential should have practiced effective 
contraception methods as described below for 2 months prior to the first dose of the study 
vaccine, through 2 months after the second dose of the study vaccine. 

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Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependenta  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation  
• 
Oral. 
• 
Intravaginal. 
• 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral. 
• 
Injectable.  
Highly Effective Methods That Are User Independenta  
• 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device. 
• 
Intrauterine hormone-releasing system. 
• 
Bilateral procedural tubal occlusion, such as ligation. 
Vasectomized partner  
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants participating in 
clinical studies.  
 
Pregnancy Testing: 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test. 
• Additional pregnancy testing at times specified in the SoA (Section 1.3) during the 
treatment period. 
Collection of Pregnancy Information 
Female Participants who become pregnant  
• The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on the 

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appropriate form and submitted to the Sponsor or designee within 24 hours of learning of a 
participant’s pregnancy. The participant will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant and the 
neonate and the information will be forwarded to the Sponsor or designee. Generally, 
follow-up will not be required for longer than 6 to 8 weeks beyond the estimated delivery 
date. Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
will be reported as an AE or SAE. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (i.e., spontaneous abortion, stillbirth, neonatal death, 
or congenital anomaly [including that in an aborted fetus, stillbirth, or neonatal death]), the 
investigator will report according to the SAE reporting procedures described in 
Section 10.5. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
treatment by the investigator will be reported to the Sponsor or designee as described in 
Section 10.5.3. While the investigator is not obligated to actively seek this information in 
former participants, he or she may learn of an SAE through spontaneous reporting.  
• Any female participant who becomes pregnant after the first study intervention dose must 
not receive the second dose of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
 
 

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10.7 Appendix 7: Abbreviations and Glossary of Terms 
Table 14 
Abbreviations 
Abbreviation 
Definition 
AE 
Adverse event 
AESI 
Adverse Events of Special Interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
BARDA 
Biomedical Advanced Research and Development Authority 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
CTR 
Clinical Trial Regulation 
CVV 
Candidate Vaccine Virus 
eCRF 
Electronic case report form 
DS 
Diary set 
EOS 
End of study 
ES 
Exposed set 
EU 
European Union 
FDA 
Food and Drug Administration 
FSFV 
First subject first visit 
FSH 
Follicle-stimulating Hormone 
GCP 
Good Clinical Practice 
GMFR 
Geometric Mean Fold Rise 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline 
H5N8 
Monovalent Influenza A/Astrakhan/3212/2020-like virus 
HA 
Hemagglutinin  
HI 
Hemagglutination Inhibition 
HRT 
Hormone replacement therapy 

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Abbreviation 
Definition 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
iSRC 
Internal safety review committee 
IRB 
Institutional Review Board 
IWRS 
Interactive Voice/Web Response System 
LAR 
Legally authorized representative 
LL 
Lower limit 
LLOQ 
Lower limit of quantitation 
LSLV 
Last subject last visit 
MAE 
Medically Attended Adverse Events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MN 
Microneutralization 
PI 
Principal Investigator 
pIMD 
Potential Immune-Mediated Disease 
PPS 
Per protocol set 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SC 
Seroconversion 
SCR 
Seroconversion Rate 
SoA 
Schedule of Activities 
SP 
Seroprotection 
SPR 
Seroprotection Rate 
SRT 
Safety Review Team 
TC 
Telephone Contact 
US 
United States 
VR 
Vaccine Response 

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Abbreviation 
Definition 
VRR 
Vaccine Response Rate 
WOCBP 
Women of Childbearing Potential 
 

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Table 15 
Glossary of Terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the use 
of a medicinal product, whether or not considered related to 
the medicinal product.  
An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, 
or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal 
products, this also includes failure to produce expected 
benefits (i.e., lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are kept 
unaware of the intervention assignment in order to reduce 
the risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the trial, and only 
when the data are cleaned to an acceptable level of quality 
will appropriate personnel be unblinded or when required in 
case of a serious AEs  
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned.  
Caregiver: 
A ‘caregiver’ is a person who has a continuous caring role 
for a participant or may be a person having substantial 
periods of contact with a participant and/or is engaged in 
his/her daily health care (e.g., a relative of the participant 
including family members or friends).  
In the context of this study, a caregiver can be appointed by 
the participant to oversee and support the participant’s 
compliance with protocol-specific procedures (such as 
transcribing responses to diaries, receiving phone calls, 
planning study visits, etc.). However, at no time, the 
caregiver should evaluate the participant’s health status 
while answering diaries or make decisions on behalf of the 
participant. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 

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Enrolled participant: 
‘Enrolled’ means a participant’s agreement to participate in 
a clinical study following completion of the informed 
consent process. Potential participants who are screened for 
determining eligibility for the study, but do not participate 
in the study, are not considered enrolled, unless otherwise 
specified by the protocol.  
Refer to the Section 9.3 of the protocol for the definition of 
‘enrolled set’ applicable to the study.  
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, included 
in the per protocol analysis. 
Immunological correlate of 
protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intercurrent medical 
condition: 
A condition that has the capability of altering the immune 
response to the study vaccine or is confirmed to have an 
alteration of the participant’s initial immune status. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Intervention: 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Investigator: 
A person responsible for the conduct of the clinical trial at a 
trial site. If a trial is conducted by a team of individuals at a 
trial site, the investigator is the responsible leader of the 
team and may be called the Principal Investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified individual 
or party to perform those trial-related duties and functions. 
Participant number: 
A unique identification number assigned to each participant 
who consents to participate in the study. 
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. 
Protocol amendment: 
The International Council on Harmonisation (ICH) defines 
a protocol amendment as: ‘A written description of a 

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change(s) to or formal clarification of a protocol.’ GSK 
further details this to include a change to an approved 
protocol that affects the safety of participants, scope of the 
investigation, study design, or scientific integrity of the 
study. 
Randomization: 
Process of random attribution of intervention to participants 
to reduce selection bias. 
Site Monitor: 
An individual assigned by the Sponsor and responsible for 
assuring proper conduct of clinical studies at 1 or more 
investigational sites. 
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 trial necessary for the reconstruction 
and evaluation of the trial. Source data are contained in 
source documents (original records or certified copies). 
Source documents: 
Original legible documents, data, and records (e.g., hospital 
records, clinical and office charts, laboratory notes, 
memoranda, participants' diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified 
after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-
rays, participant files, and records kept at the pharmacy, 
laboratories and at medico-technical departments involved 
in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
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. 
 
 

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10.8 Appendix 8: List of Potential Immune-Mediated Diseases  
The GSK list of pIMDs is based on MedDRA version 26.1. 
Table 16 
GSK List of pIMD MedDRA Terms  
MedDRA Term Name 
Term Level 
Acute cutaneous lupus erythematosus 
PT 
Acute disseminated encephalomyelitis 
PT 
Acute febrile neutrophilic dermatosis 
PT 
Acute flaccid myelitis 
PT 
Acute haemorrhagic leukoencephalitis 
PT 
Acute haemorrhagic oedema of infancy 
PT 
Acute macular neuroretinopathy 
PT 
Acute motor axonal neuropathy 
PT 
Acute motor-sensory axonal neuropathy 
PT 
Acute necrotising myelitis 
PT 
Addison's disease 
PT 
Administration site vasculitis 
PT 
AGEP-DRESS overlap 
PT 
Alopecia areata 
PT 
Alveolar proteinosis 
PT 
Ankylosing spondylitis 
PT 
Antibody-dependent enhancement 
PT 
Anti-glomerular basement membrane disease 
PT 
Anti-LRP2 nephropathy 
PT 
Anti-myelin-associated glycoprotein associated polyneuropathy 
PT 
Anti-neutrophil cytoplasmic antibody positive vasculitis 
PT 
Antiphospholipid syndrome 
PT 
Anti-RNA polymerase III antibody increased 
PT 
Anti-RNA polymerase III antibody positive 
PT 
Antisynthetase syndrome 
PT 
Aortitis 
PT 
Application site vasculitis 
PT 
Arteritis 
PT 
Arteritis coronary 
PT 

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MedDRA Term Name 
Term Level 
Arthritis enteropathic 
PT 
Arthritis reactive 
PT 
ASIA syndrome 
PT 
Atrophic thyroiditis 
PT 
Autoimmune anaemia 
PT 
Autoimmune aplastic anaemia 
PT 
Autoimmune arthritis 
PT 
Autoimmune blistering disease 
PT 
Autoimmune cerebellar ataxia 
PT 
Autoimmune cholangitis 
PT 
Autoimmune colitis 
PT 
Autoimmune demyelinating disease 
PT 
Autoimmune dermatitis 
PT 
Autoimmune disorder 
PT 
Autoimmune encephalopathy 
PT 
Autoimmune endocrine disorder 
PT 
Autoimmune enteropathy 
PT 
Autoimmune eye disorder 
PT 
Autoimmune haemolytic anaemia 
PT 
Autoimmune heparin-induced thrombocytopenia 
PT 
Autoimmune hepatitis 
PT 
Autoimmune hyperlipidaemia 
PT 
Autoimmune hypothyroidism 
PT 
Autoimmune inner ear disease 
PT 
Autoimmune lung disease 
PT 
Autoimmune lymphoproliferative syndrome 
PT 
Autoimmune myocarditis 
PT 
Autoimmune myositis 
PT 
Autoimmune nephritis 
PT 
Autoimmune neuropathy 
PT 
Autoimmune neutropenia 
PT 
Autoimmune pancreatitis 
PT 
Autoimmune pancytopenia 
PT 

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MedDRA Term Name 
Term Level 
Autoimmune pericarditis 
PT 
Autoimmune retinopathy 
PT 
Autoimmune thyroid disorder 
PT 
Autoimmune thyroiditis 
PT 
Autoimmune uveitis 
PT 
Autoinflammatory disease 
PT 
Axial spondyloarthritis 
PT 
Axonal and demyelinating polyneuropathy 
PT 
Axonal neuropathy 
PT 
Behcet's syndrome 
PT 
Bell's palsy 
PT 
Bickerstaff's encephalitis 
PT 
Birdshot chorioretinopathy 
PT 
Brachial plexopathy 
PT 
Bulbar palsy 
PT 
C1q nephropathy 
PT 
CANOMAD syndrome 
PT 
Capillaritis 
PT 
Capillary leak syndrome 
PT 
Caplan's syndrome 
PT 
Cardiac sarcoidosis 
PT 
Central nervous system lupus 
PT 
Central nervous system vasculitis 
PT 
Cerebral arteritis 
PT 
Cholangitis sclerosing 
PT 
Chronic autoimmune glomerulonephritis 
PT 
Chronic cutaneous lupus erythematosus 
PT 
Chronic inflammatory demyelinating polyradiculoneuropathy 
PT 
Chronic lymphocytic inflammation with pontine perivascular enhancement 
responsive to steroids 
PT 
Chronic pigmented purpura 
PT 
Clinically isolated syndrome 
PT 
Coeliac disease 
PT 

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MedDRA Term Name 
Term Level 
Cogan's syndrome 
PT 
Cold type haemolytic anaemia 
PT 
Colitis erosive 
PT 
Colitis microscopic 
PT 
Colitis ulcerative 
PT 
Collagen-vascular disease 
PT 
Concentric sclerosis 
PT 
Coombs positive haemolytic anaemia 
PT 
Cranial nerve disorder 
PT 
Cranial nerve palsies multiple 
PT 
Cranial nerve paralysis 
PT 
CREST syndrome 
PT 
Crohn's disease 
PT 
Cutaneous lupus erythematosus 
PT 
Cutaneous sarcoidosis 
PT 
Cutaneous vasculitis 
PT 
Demyelinating polyneuropathy 
PT 
Demyelination 
PT 
Dermatitis bullous 
PT 
Dermatitis herpetiformis 
PT 
Dermatomyositis 
PT 
Diffuse vasculitis 
PT 
Encephalitis allergic 
PT 
Encephalitis autoimmune 
PT 
Encephalitis brain stem 
PT 
Encephalitis haemorrhagic 
PT 
Encephalitis periaxialis diffusa 
PT 
Encephalitis post immunisation 
PT 
Encephalitis toxic 
PT 
Encephalomyelitis 
PT 
Endocrine ophthalmopathy 
PT 
Enhanced respiratory disease 
PT 
Enteropathic spondylitis 
PT 

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MedDRA Term Name 
Term Level 
Eosinophilic fasciitis 
PT 
Eosinophilic granulomatosis with polyangiitis 
PT 
Erythema induratum 
PT 
Erythema multiforme 
PT 
Erythema nodosum 
PT 
Evans syndrome 
PT 
Expanded disability status scale score decreased 
PT 
Expanded disability status scale score increased 
PT 
Facial paralysis 
PT 
Facial paresis 
PT 
Felty's syndrome 
PT 
Fibrillary glomerulonephritis 
PT 
Fulminant type 1 diabetes mellitus 
PT 
Giant cell arteritis 
PT 
Giant cell myocarditis 
PT 
Glomerulonephritis membranoproliferative 
PT 
Glomerulonephritis membranous 
PT 
Glomerulonephritis rapidly progressive 
PT 
Glossopharyngeal nerve paralysis 
PT 
Goodpasture's syndrome 
PT 
Gout 
PT 
Gouty arthritis 
PT 
Gouty tophus 
PT 
Granulomatosis with polyangiitis 
PT 
Granulomatous dermatitis 
PT 
Graves' disease 
PT 
Guillain-Barre syndrome 
PT 
Haemorrhagic occlusive retinal vasculitis 
PT 
Haemorrhagic vasculitis 
PT 
Hashimoto's encephalopathy 
PT 
Hashitoxicosis 
PT 
Henoch-Schonlein purpura 
PT 
Henoch-Schonlein purpura nephritis 
PT 

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MedDRA Term Name 
Term Level 
Hypersensitivity vasculitis 
PT 
Hypoglossal nerve paralysis 
PT 
Hypoglossal nerve paresis 
PT 
Idiopathic inflammatory myopathy 
PT 
Idiopathic interstitial pneumonia 
PT 
Idiopathic pulmonary fibrosis 
PT 
IgA nephropathy 
PT 
IgM nephropathy 
PT 
IIIrd nerve paralysis 
PT 
IIIrd nerve paresis 
PT 
Immune effector cell-associated HLH-like syndrome 
PT 
Immune thrombocytopenia 
PT 
Immune-complex membranoproliferative glomerulonephritis 
PT 
Immune-mediated adrenal insufficiency 
PT 
Immune-mediated adverse reaction 
PT 
Immune-mediated arthritis 
PT 
Immune-mediated cholangitis 
PT 
Immune-mediated cholestasis 
PT 
Immune-mediated cystitis 
PT 
Immune-mediated cytopenia 
PT 
Immune-mediated dermatitis 
PT 
Immune-mediated encephalitis 
PT 
Immune-mediated encephalopathy 
PT 
Immune-mediated endocrinopathy 
PT 
Immune-mediated enterocolitis 
PT 
Immune-mediated gastritis 
PT 
Immune-mediated hepatic disorder 
PT 
Immune-mediated hepatitis 
PT 
Immune-mediated hyperthyroidism 
PT 
Immune-mediated hypophysitis 
PT 
Immune-mediated hypothyroidism 
PT 
Immune-mediated lung disease 
PT 
Immune-mediated myasthenia gravis 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
100 
MedDRA Term Name 
Term Level 
Immune-mediated myelitis 
PT 
Immune-mediated myocarditis 
PT 
Immune-mediated myositis 
PT 
Immune-mediated nephritis 
PT 
Immune-mediated neurological disorder 
PT 
Immune-mediated neuropathy 
PT 
Immune-mediated oesophagitis 
PT 
Immune-mediated optic neuritis 
PT 
Immune-mediated pancreatitis 
PT 
Immune-mediated pancytopenia 
PT 
Immune-mediated pericarditis 
PT 
Immune-mediated polyserositis 
PT 
Immune-mediated renal disorder 
PT 
Immune-mediated scleritis 
PT 
Immune-mediated thyroiditis 
PT 
Immune-mediated uveitis 
PT 
Immune-mediated vasculitis 
PT 
Immunoglobulin G4 related disease 
PT 
Inclusion body myositis 
PT 
Inflammatory bowel disease 
PT 
Injection site vasculitis 
PT 
Insulin autoimmune syndrome 
PT 
Interstitial granulomatous dermatitis 
PT 
Interstitial lung disease 
PT 
Intramyelinic oedema 
PT 
IVth nerve paralysis 
PT 
IVth nerve paresis 
PT 
Juvenile idiopathic arthritis 
PT 
Juvenile polymyositis 
PT 
Juvenile psoriatic arthritis 
PT 
Juvenile spondyloarthritis 
PT 
Kawasaki's disease 
PT 
Keratoderma blenorrhagica 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
101 
MedDRA Term Name 
Term Level 
Langerhans' cell histiocytosis 
PT 
Laryngeal rheumatoid arthritis 
PT 
Latent autoimmune diabetes in adults 
PT 
Leukoencephalomyelitis 
PT 
Leukoencephalopathy 
PT 
Lewis-Sumner syndrome 
PT 
Lichen planopilaris 
PT 
Lichen planus 
PT 
Lichen planus pemphigoides 
PT 
Linear IgA disease 
PT 
Liver sarcoidosis 
PT 
Loefgren syndrome 
PT 
Lumbosacral radiculoplexus neuropathy 
PT 
Lupoid hepatic cirrhosis 
PT 
Lupus anticoagulant hypoprothrombinaemia syndrome 
PT 
Lupus cystitis 
PT 
Lupus encephalitis 
PT 
Lupus endocarditis 
PT 
Lupus enteritis 
PT 
Lupus hepatitis 
PT 
Lupus myocarditis 
PT 
Lupus myositis 
PT 
Lupus nephritis 
PT 
Lupus pancreatitis 
PT 
Lupus pleurisy 
PT 
Lupus pneumonitis 
PT 
Lupus vasculitis 
PT 
Lupus-like syndrome 
PT 
Lymphocytic hypophysitis 
PT 
MAGIC syndrome 
PT 
Marburg's variant multiple sclerosis 
PT 
Marine Lenhart syndrome 
PT 
Melkersson-Rosenthal syndrome 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
102 
MedDRA Term Name 
Term Level 
Membranous-like glomerulopathy with masked IgG-kappa deposits 
PT 
Mesangioproliferative glomerulonephritis 
PT 
Metastatic cutaneous Crohn's disease 
PT 
Microscopic enteritis 
PT 
Microscopic polyangiitis 
PT 
Miller Fisher syndrome 
PT 
Mixed connective tissue disease 
PT 
Mononeuritis 
PT 
Mononeuropathy multiplex 
PT 
Morphoea 
PT 
Morvan syndrome 
PT 
Mucous membrane pemphigoid 
PT 
Multifocal motor neuropathy 
PT 
Multiple sclerosis 
PT 
Multiple sclerosis pseudo relapse 
PT 
Multiple sclerosis relapse 
PT 
Multiple sclerosis relapse prophylaxis 
PT 
Multisystem inflammatory syndrome 
PT 
Multisystem inflammatory syndrome in adults 
PT 
Multisystem inflammatory syndrome in children 
PT 
Muscular sarcoidosis 
PT 
Myasthenia gravis 
PT 
Myasthenia gravis crisis 
PT 
Myasthenic syndrome 
PT 
Myelin oligodendrocyte glycoprotein antibody-associated disease 
PT 
Myelitis 
PT 
Myelitis transverse 
PT 
Myocarditis 
PT 
Myopericarditis 
PT 
Narcolepsy 
PT 
Neuralgic amyotrophy 
PT 
Neuritis 
PT 
Neuritis cranial 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
103 
MedDRA Term Name 
Term Level 
Neuromyelitis optica pseudo relapse 
PT 
Neuromyelitis optica spectrum disorder 
PT 
Neuropsychiatric lupus 
PT 
Neurosarcoidosis 
PT 
Nodular vasculitis 
PT 
Noninfectious myelitis 
PT 
Noninfective encephalitis 
PT 
Noninfective encephalomyelitis 
PT 
Noninfective oophoritis 
PT 
Ocular myasthenia 
PT 
Ocular pemphigoid 
PT 
Ocular sarcoidosis 
PT 
Ocular vasculitis 
PT 
Oculofacial paralysis 
PT 
Olfactory nerve disorder 
PT 
Optic ischaemic neuropathy 
PT 
Optic neuritis 
PT 
Optic neuropathy 
PT 
Optic perineuritis 
PT 
Orexin deficiency 
PT 
Overlap syndrome 
PT 
Palindromic rheumatism 
PT 
Palisaded neutrophilic granulomatous dermatitis 
PT 
Palpable purpura 
PT 
Panencephalitis 
PT 
Paresis cranial nerve 
PT 
Pemphigoid 
PT 
Pemphigus 
PT 
Pericarditis 
PT 
Pericarditis lupus 
PT 
Pericarditis rheumatic 
PT 
Peripheral spondyloarthritis 
PT 
Peritonitis lupus 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
104 
MedDRA Term Name 
Term Level 
Pernicious anaemia 
PT 
Pleuroparenchymal fibroelastosis 
PT 
Polyarteritis nodosa 
PT 
Polychondritis 
PT 
Polyglandular autoimmune syndrome type I 
PT 
Polyglandular autoimmune syndrome type II 
PT 
Polyglandular autoimmune syndrome type III 
PT 
Polymyalgia rheumatica 
PT 
Polymyositis 
PT 
Polyneuropathy idiopathic progressive 
PT 
Primary biliary cholangitis 
PT 
Primary progressive multiple sclerosis 
PT 
Proctitis ulcerative 
PT 
Progressive facial hemiatrophy 
PT 
Progressive multiple sclerosis 
PT 
Progressive relapsing multiple sclerosis 
PT 
Psoriasis 
PT 
Psoriatic arthropathy 
PT 
Pulmonary fibrosis 
PT 
Pulmonary renal syndrome 
PT 
Pulmonary sarcoidosis 
PT 
Pulmonary vasculitis 
PT 
Pyoderma gangrenosum 
PT 
Pyostomatitis vegetans 
PT 
Radiculitis brachial 
PT 
Radiologically isolated syndrome 
PT 
Rasmussen encephalitis 
PT 
Raynaud's phenomenon 
PT 
Relapsing multiple sclerosis 
PT 
Relapsing-remitting multiple sclerosis 
PT 
Renal arteritis 
PT 
Renal vasculitis 
PT 
Retinal occlusive vasculitis 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
105 
MedDRA Term Name 
Term Level 
Retinal vasculitis 
PT 
Reynold's syndrome 
PT 
Rheumatic brain disease 
PT 
Rheumatic disorder 
PT 
Rheumatoid arthritis 
PT 
Rheumatoid arthritis-associated interstitial lung disease 
PT 
Rheumatoid bursitis 
PT 
Rheumatoid lung 
PT 
Rheumatoid meningitis 
PT 
Rheumatoid neutrophilic dermatosis 
PT 
Rheumatoid nodule 
PT 
Rheumatoid pleuritis 
PT 
Rheumatoid scleritis 
PT 
Rheumatoid vasculitis 
PT 
Rhupus syndrome 
PT 
Sarcoidosis 
PT 
Sarcoidosis of lymph node 
PT 
Satoyoshi syndrome 
PT 
Sclerodactylia 
PT 
Scleroderma 
PT 
Scleroderma associated digital ulcer 
PT 
Scleroderma renal crisis 
PT 
Secondary progressive multiple sclerosis 
PT 
Segmented hyalinising vasculitis 
PT 
Shrinking lung syndrome 
PT 
Silent thyroiditis 
PT 
Sjogren's syndrome 
PT 
SJS-TEN overlap 
PT 
SLE arthritis 
PT 
Spondylitis 
PT 
Spondyloarthropathy 
PT 
Stevens-Johnson syndrome 
PT 
Still's disease 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
106 
MedDRA Term Name 
Term Level 
Stoma site vasculitis 
PT 
Subacute cutaneous lupus erythematosus 
PT 
Subacute inflammatory demyelinating polyneuropathy 
PT 
Susac's syndrome 
PT 
Sympathetic ophthalmia 
PT 
Systemic lupus erythematosus 
PT 
Systemic lupus erythematosus disease activity index abnormal 
PT 
Systemic lupus erythematosus disease activity index decreased 
PT 
Systemic lupus erythematosus disease activity index increased 
PT 
Systemic lupus erythematosus rash 
PT 
Systemic scleroderma 
PT 
Systemic sclerosis pulmonary 
PT 
Takayasu's arteritis 
PT 
Terminal ileitis 
PT 
Testicular autoimmunity 
PT 
Thromboangiitis obliterans 
PT 
Thrombocytopenic purpura 
PT 
Thrombosis with thrombocytopenia syndrome 
PT 
Thrombotic thrombocytopenic purpura 
PT 
Tongue paralysis 
PT 
Toxic epidermal necrolysis 
PT 
Trigeminal nerve paresis 
PT 
Trigeminal palsy 
PT 
Tubulointerstitial nephritis and uveitis syndrome 
PT 
Tumefactive multiple sclerosis 
PT 
Type 1 diabetes mellitus 
PT 
Uhthoff's phenomenon 
PT 
Ulcerative keratitis 
PT 
Undifferentiated connective tissue disease 
PT 
Undifferentiated spondyloarthritis 
PT 
Urticarial vasculitis 
PT 
Uveitis 
PT 
Vaccination site vasculitis 
PT 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
107 
MedDRA Term Name 
Term Level 
Vagus nerve paralysis 
PT 
Vascular purpura 
PT 
Vasculitic rash 
PT 
Vasculitic ulcer 
PT 
Vasculitis 
PT 
Vasculitis gastrointestinal 
PT 
Vasculitis necrotising 
PT 
VIth nerve paralysis 
PT 
VIth nerve paresis 
PT 
Vitiligo 
PT 
Vocal cord paralysis 
PT 
Vocal cord paresis 
PT 
Vogt-Koyanagi-Harada disease 
PT 
Warm autoimmune haemolytic anaemia 
PT 
XIth nerve paralysis 
PT 
Abbreviations: LLT=lowest level term; PT=preferred term. 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
108 
10.9 Appendix 9: Protocol and Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the table of contents. 
Amendment 1.0: 23 June 2023 
Overall Rationale for the Amendment 1.0: 
This protocol has been amended to extend the collection of medically attended adverse events 
(MAEs) and to include a 30-minute observation period after each vaccination as required by 
the US Food and Drug Administration (FDA).  
Added text in bold italic, deleted text in strikethrough.  
Section # and Name 
Description of Change from 
Original Protocol to 
Amendment 1.0 
Brief Rationale 
1.1 Synopsis,   
1.2 Study Design, 
1.3 Schedule of Activities, 
3.0 Objectives and 
Endpoints, 
8.5.1 Time Period and 
Frequency for Collecting 
AE, SAE, pIMD 
Information, 
9.4.3.2 Safety, 
9.5.1.1 Interim Analysis 
at Day 43, 
9.5.1.2 Final Analysis (6 
Months Post Dose 2) 
 
Extended collection of MAEs to 
Visit 6/EOS (6 months post dose 2) 
FDA requirement  
1.3 Schedule of Activities  
Added Time Point task to Table 1: 
30-minute observation period 
after each vaccine administration. 
  
FDA requirement  
 
Deleted collection of diary card at 
Visit 6/EOS  
Diary cards are returned at Visit 5 
(Day 43) 
8.3.6 Post-Vaccination 
Observation Period 
Section added  
FDA requirement  
8.5.2 Method of Detecting 
AEs and SAEs 
Added text:  
Participants must be made aware 
of the requirement to report any 
new medical condition or 
worsening of any pre-existing 
medical condition requiring 
contact with a healthcare 
professional to the site staff.  
FDA requirement 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
109 
Section # and Name 
Description of Change from 
Original Protocol to 
Amendment 1.0 
Brief Rationale 
Global document update 
Version control including version 
number and summary of changes 
were added to this document and 
minor edits have been made for 
clarity. 
Version control, minor clarifications 
 
 
 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
110 
Amendment 2.0: 22 August 2023 
Overall Rationale for the Amendment 2.0: 
This protocol has been amended to replace the table titled ‘List of potential Immune-Mediated 
Diseases (pIMDs)’ with an entire listing of pIMD terms, based on the GSK MedDRA query 
listing, as requested by the US Food and Drug Administration (FDA).  
Added text in bold italic, deleted text in strikethrough.  
Section # and Name 
Description of Changes from 
Amendment 1.0 to Amendment 2.0 
Brief Rationale 
8.5.7.1 Potential Immune-
Mediated Diseases 
Moved pIMD table to Appendix 8 
To improve flow and readability as the 
pIMD table length has increased. 
9.3 Analysis Sets 
Updated text in Table 9 Analysis 
Sets: 
• 
Results from a serological 
blood sample occurred after 
intercurrent conditions that may 
interfere with immunogenicity 
(i.e., immunosuppressive, or 
immunodeficient conditions, or 
malignancy) or after a 
prohibited concomitant 
medication/vaccination  
 
To improve clarity for investigator. 
9.4.5 Demography and 
Baseline Characteristic 
Analysis 
Edited text: 
Demographic characteristics (age, 
gender, race, center, country, 
ethnicity, and occupation) will be 
tabulated per study group for each 
analysis set ES and PPS, as 
described in the SAP. 
Clarification 
10.1.7 Committees 
Structure 
A SRT is in place for each GSK 
product. It comprises of a global 
cross-functional team responsible 
for the ongoing assessment of 
benefit-risk for a product. The SRT 
contribute to the continual 
assessment of incoming new 
efficacy and safety information. 
Added GSK SRT template text. 
10.5.3.1 Assessment of 
Intensity and Causality 
Deleted text in possible contributing 
factor for SAE: 
Lack of efficacy of the 
vaccine/product, if applicable 
Removed text as efficacy assessment is 
not a primary objective. 
10.6.2 Contraception 
Guidance  
Highly Effective 
Contraceptive Methods 
That Are User Dependent 
Updated text: 
Bilateral procedural tubal occlusion, 
such as ligation   
Clarification  

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
111 
Section # and Name 
Description of Changes from 
Amendment 1.0 to Amendment 2.0 
Brief Rationale 
 
Deleted footnote and corresponding 
superscript ‘b’: 
b Hormonal contraception may be 
susceptible to interaction with the 
study intervention, which may 
reduce the efficacy of the 
contraceptive method. In this case, 2 
highly effective methods of 
contraception should be utilized 
during the treatment period and for at 
least 2 months after the last dose of 
study intervention.  
The AS03 adjuvanted pandemic 
influenza vaccines have not been 
associated with reduced efficacy of 
hormonal contraception.  
10.8 Appendix 8: List of 
Potential Immune-
Medicated Disease 
Added Appendix 8 and Table 16 
GSK List of pIMDs MedDRA Terms 
To meet FDA request. 
10.9 Appendix 9: Protocol 
and Amendment History 
Added Appendix 9  
Version control 
Global document updates 
Updated cross links and references to 
the pIMD table  
Version and summary of changes 
were revised  
Version control 
 
 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
112 
11.0 REFERENCES 
1. Pyankova, OG, Susloparov, IM, Moiseeva, AA, et al. Isolation of clade 2.3.4.4b A(H5N8), 
a highly pathogenic avian influenza virus, from a worker during an outbreak on a 
poultry farm, Russia, December 2020: Euro Surveill. 2021 Jun;26(24):2100439. 
2. World Health Organization (WHO, 26 February 2021). Human infection with avian 
influenza A (H5N8) - Russian Federation. Accessed 31 August 2022, 
https://www.who.int/emergencies/disease-outbreak-news/item/2021-DON313. 
3. 2022 detections of highly pathogenic avian influenza (no date) USDA APHIS | 2022 
Detections of Highly Pathogenic Avian Influenza. Available at: 
https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-
information/avian/avian-influenza/2022-hpai (Accessed: January 9, 2023). 
4. CDC Newsroom U.S. case of human avian influenza A(H5) reported. 28 April 2022. 
https://www.cdc.gov/media/releases/2022/s0428-avian-flu.html Accessed 13 Oct 
2022. 
5. Winokur PL, Hegmann TE, Keitel WA, et al. DMID 15-0064 Study Group. Safety and 
Immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine given 
with and without AS03 or MF59 adjuvants in healthy adults. Clin Infect Dis. 
2023 Jan 5:ciac983. 
6. Neuzil KM, Anderson EJ, Frenck RW, et al. Influenza A/H5N8 Virus Vaccine Group. 
Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: 
Durability and Cross-reactivity of Antibody Responses. Clin Infect Dis. 
2023 Jan 5:ciac982. 
7. Chu DW, Hwang SJ, Lim FS, et al.; H5N1 Flu Study Group for Hong Kong, Singapore, 
Taiwan and Thailand. Immunogenicity and tolerability of an AS03(A)-adjuvanted 
prepandemic influenza vaccine: a phase III study in a large population of Asian adults. 
Vaccine. 2009;27-7428–7435. 
8. Díez-Domingo J, Garcés-Sanchez M, Baldó JM, et al. Immunogenicity and Safety of H5N1 
A/Vietnam/1194/2004 (Clade 1) AS03-adjuvanted prepandemic candidate influenza 
vaccines in children aged 3 to 9 years: a phase II, randomized, open, controlled study. 
Pediatr Infect Dis J. 2010;29:e35–e46. 
9. Kosalaraksa P, Jeanfreau R, Frenette L, et al. AS03B-adjuvanted H5N1 influenza vaccine 
in children 6 months through 17 years of age: a phase 2/3 randomized, placebo-
controlled, observer-blinded trial. J Infect Dis. 2015;211:801–810. 
10. Langley JM, Frenette L, Ferguson L, et al. Safety and cross-reactive immunogenicity of 
candidate AS03-adjuvanted prepandemic H5N1 influenza vaccines: a randomized 
controlled phase 1/2 trial in adults. J Infect Dis. 2010;201:1644–1653. 
11. Langley JM, Risi G, Caldwell M, et al. Dose-sparing H5N1 A/Indonesia/05/2005 
pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-
controlled, randomized study. J Infect Dis. 2011;203:1729–1738. 

CONFIDENTIAL 
 
Protocol 219833 
Amendment 3.0 
 
113 
12. Leroux-Roels I, Borkowski A, Vanwolleghem T, et al. Antigen sparing and cross-reactive 
immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a 
randomised controlled trial. Lancet. 2007;370:580–589. 
13. Nolan T, Izurieta P, Lee BW, et al. Heterologous prime-boost vaccination using an 
AS03B-adjuvanted influenza A(H5N1) vaccine in infants and children <3 years of age. 
J Infect Dis. 2014;210:1800–1810. 
14. Vaughn DW, Seifert H, Hepburn A, et al. Safety of AS03-adjuvanted inactivated split 
virion A(H1N1)pdm09 and H5N1 influenza virus vaccines administered to adults: 
pooled analysis of 28 clinical trials. Hum Vaccin Immunother. 2014;10:2942–2957. 
15. Rimmelzwaan GF, McElhaney JE. Correlates of protection: novel generations of influenza 
vaccines. Vaccine. 2008;26 (Suppl 4): D41-4. 
16. Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza 
vaccination. Vir Res. 2004;103:133-8. 
17. Beyer WE, Palache AM, Baljet M, Masurel N. Antibody induction by influenza vaccines 
in the elderly: a review of the literature. Vaccine. 1989;7:385-94. 
18. Borchers AT, Chang C, Gershwin ME, et al. Respiratory syncytial virus – a 
comprehensive review. Clin Rev Allergy Immunol. 2013;45:331-79. 
19. Pérez-Losada M, Posada D, Arenas M, et al. Ethnic differences in the adaptation rate of 
HIV gp120 from a vaccine trial. Retrovirology. 2009;6:67. 
20. Kollmann TR. Variation between Populations in the Innate Immune Response to Vaccine 
Adjuvants. Front Immunol. 2013;4:81. 
21. World Health Organization. (2011). Manual for the laboratory diagnosis and virological 
surveillance of influenza. World Health Organization. 
https://apps.who.int/iris/handle/10665/44518 
22. US Department of Health and Human Services, Food and Drug Administration. Guidance 
for the Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials. 2007. 
 

114 
 
Signature of Investigator 
PROTOCOL TITLE: A Phase I/II observer-blind, randomized, multi-center trial to evaluate 
the safety and immunogenicity of different formulations of monovalent 
Influenza A/Astrakhan/3212/2020-like (H5N8) virus vaccine with AS03 adjuvant system, 
given as a two-dose series to adults 18 to 64 years of age and 65 years of age and older. 
PROTOCOL NO: 
219833 
VERSION:  
 
Protocol Amendment 3.0 
This protocol is a confidential communication of GSK. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from the 
Sponsor. 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy to IQVIA. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
___________________________            Date:  ________ 
Printed Name:  
 
___________________________ 
Investigator Title:                   ___________________________ 
 
Name/Address of Center:               
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________