Clinical trial NCT03312231
Conditions: Avian Influenza Influenza Immunisation
Keywords: A/H7N9 Immunogenicity Influenza Safety Sanofi Pasteur Vaccine
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2018-02-14; Completion date: 2019-09-26
Enrollment: 720 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females 19 years and older that is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) administered at different dosages given with AS03 adjuvant and phosphate buffered saline (PBS) diluent, with AS03 adjuvant only, and without adjuvant. Eligible subjects will be randomized into 5 study groups, stratified by age. The study will enroll up to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older. Study duration is approximately 16 months with subject participation duration approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient.

Detailed description:
This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females 19 years and older. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) administered at different dosages given with or without adjuvant. 3.75 mcg of HA per dose will be administered with phosphate buffered saline (PBS) diluent and AS03 adjuvant, 7.5 mcg and 15 mcg of HA per dose will be administered with AS03 adjuvant only, and 15 mcg and 45 mcg of HA per dose will be administered without adjuvant. Eligible subjects will be randomized into one of 5 study groups, stratified by age. The study will enroll up to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older. The study duration is approximately 16 months with subject participation duration approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient. The secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant; 2) to assess medically-attended adverse events (MAAEs) including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant; 3) to assess the serum HAI and Neut antibody responses approximately 7 and 21 days following receipt of a single dose, and approximately 7 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient.

Arms: arm 1: 3.75 mcg of H7N9 vaccine with PBS diluent plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older) arm 2: 7.5 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older) arm 3: 15 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older) arm 4: 15 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older) arm 5: 45 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older)
Interventions: intervention 1: AS03 intervention 2: Inactivated influenza H7N9 vaccine intervention 3: Phosphate Buffered Saline (PBS) diluent
Intervention descriptions: intervention 1: Oil-in-water emulsion based adjuvant system. intervention 2: Monovalent 2017 H7N9 inactivated influenza vaccine intervention 3: Diluent for 2017 Monovalent Inactivated Influenza A/H7N9 virus vaccine (2017 H7N9 IIV)

Protocol documents:
Prot_000.pdf: 
A Phase II Study in Healthy Adults 19 Years and Older to Assess the Safety, 
Reactogenicity and Immunogenicity of a Sanofi Pasteur A/H7N9 Inactivated 
Influenza Vaccine Administered Intramuscularly With or Without AS03 Adjuvant 
DMID Protocol Number: 
17-0075
DMID Funding Mechanism: Vaccine and Treatment Evaluation Units 
Pharmaceutical Support: 
Sanofi Pasteur 
GlaxoSmithKline Biologicals 
IND Sponsor: Division of Microbiology and Infectious Diseases, National 
Institute of Allergy and Infectious Diseases, National Institutes of Health 
Lead Principal Investigator: Lisa A. Jackson, MD, MPH 
DMID Clinical Project Manager: Robin M. Mason, MS 
DMID Medical Monitor: Mohamed Elsafy, MD 
DMID Medical Officer: Francisco J. Leyva MD, PhD, ScM
DMID Scientific Lead: Chris Roberts, PhD 
Version: 5.0 
3 April, 2019 


DMID Protocol 17-0075 
Version 5.0 
Sanofi 2017 H7N9 with/without AS03 in Adults/Elderly 
April 3, 2019 
 
i 
STATEMENT OF COMPLIANCE 
This trial will be carried out in accordance with Good Clinical Practice (GCP) and as required by 
the following: 
• United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of 
Human Subjects 
• Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 
(Protection of Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical 
Investigators), 21 CFR Part 56 (Institutional Review Boards), 21 CFR Part 11, 
and 21 CFR Part 312 (Investigational New Drug Application), 21 CFR 812 
(Investigational Device Exemptions) 
• International Conference on Harmonisation: Good Clinical Practice (ICH E6); 62 
Federal Register 25691 (1997); and future revisions 
• Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, Report of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research 
• National Institutes of Health (NIH) Office of Extramural Research, Research 
Involving Human Subjects, as applicable 
• National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of 
Award, as applicable 
• Applicable Federal, State, and Local Regulations and Guidance 
 
 
 
 
 
 
 
 
 


DMID Protocol 17-0075 
Version 5.0 
Sanofi 2017 H7N9 with/without AS03 in Adults/Elderly 
April 3, 2019 
 
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SIGNATURE PAGE 
The signature below provides the necessary assurance that this trial will be conducted according 
to all stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal regulations and 
ICH E6 Good Clinical Practice (GCP) guidelines. 
 
I agree to conduct the study in compliance with GCP and applicable regulatory requirements. 
 
I agree to conduct the study in accordance with the current protocol and will not make changes to 
the protocol without obtaining the sponsor’s approval and IRB/IEC approval, except when 
necessary to protect the safety, rights, or welfare of subjects. 
 
Site Principal Investigator: 
 
Signed: 
 
 
Date: 
 
 
Name 
Title 
 
 
 


DMID Protocol 17-0075 
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April 3, 2019 
 
iii 
TABLE OF CONTENTS 
 
STATEMENT OF COMPLIANCE ................................................................................................. i 
SIGNATURE PAGE ...................................................................................................................... ii 
TABLE OF CONTENTS ............................................................................................................... iii 
LIST OF TABLES ........................................................................................................................ vii 
LIST OF FIGURES ..................................................................................................................... viii 
LIST OF ABBREVIATIONS ........................................................................................................ ix 
PROTOCOL SUMMARY ........................................................................................................... xiii 
1 
Key Roles ..............................................................................................................................22 
2 
Background Information and Scientific Rationale ...............................................................24 
2.1 
Background Information ...........................................................................................24 
2.1.1 Public Readiness and Emergency Preparedness Act ....................................27 
2.2 
Scientific Rationale ...................................................................................................28 
2.3 
Potential Risks and Benefits .....................................................................................30 
2.3.1 Potential Risks ..............................................................................................30 
2.3.2 Known Potential Benefits .............................................................................37 
3 
Study Objectives and Outcome Measures ............................................................................38 
3.1 
Study Objectives .......................................................................................................38 
3.1.1 Primary ..........................................................................................................38 
3.1.2 Secondary ......................................................................................................38 
3.1.3 Exploratory ...................................................................................................39 
3.2 
Study Outcome Measures .........................................................................................39 
3.2.1 Primary ..........................................................................................................39 
3.2.2 Secondary ......................................................................................................40 
3.2.3 Exploratory ...................................................................................................41 
4 
Study Design .........................................................................................................................42 
5 
Study Enrollment and Withdrawal........................................................................................44 
5.1 
Eligibility Criteria .....................................................................................................44 
5.1.1 Subject Inclusion Criteria .............................................................................44 
5.1.2 Subject Exclusion Criteria ............................................................................45 
5.2 
Treatment Assignment Procedures ...........................................................................48 
5.2.1 Enrollment and Randomization Procedures..................................................48 
5.2.2 Masking Procedures ......................................................................................49 
5.2.3 Reasons for Withdrawals and Discontinuation of Treatment .......................49 
5.2.4 Handling of Withdrawals and Discontinuation of Treatment .......................51 
5.2.5 Termination of Study ....................................................................................52 
6 
Study Intervention/Investigational Product ..........................................................................53 


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6.1 
Study Product Description ........................................................................................53 
6.1.1 Acquisition ....................................................................................................53 
6.1.2 Formulation, Storage, Packaging, and Labeling ...........................................54 
6.1.3 Study Product Storage and Stability Procedures ..........................................55 
6.2 
Dosage, Preparation, and Administration of Study Intervention/ Investigational 
Product ......................................................................................................................56 
6.3 
Modification of Study Intervention/Investigational Product for a Subject ...............57 
6.4 
Accountability Procedures for the Study Intervention/ Investigational Product ......58 
6.5 
Assessment of Subject Compliance with Study Intervention/ Investigational Product
...................................................................................................................................58 
6.6 
Concomitant Medications/Treatments ......................................................................59 
7 
Study Procedures and Evaluations ........................................................................................60 
7.1 
Clinical Evaluations ..................................................................................................60 
7.2 
Laboratory Evaluations .............................................................................................61 
7.2.1 Clinical Laboratory Evaluations ...................................................................61 
7.2.2 Special Assays or Procedures .......................................................................62 
7.2.3 Specimen Preparation, Handling, and Shipping ...........................................64 
7.2.3.1 Instructions for Specimen Preparation, Handling, and Storage ........64 
7.2.3.2 Specimen Shipment ..........................................................................65 
8 
Study Schedule......................................................................................................................66 
8.1 
Screening (Optional) and Enrollment Visits .............................................................66 
8.1.1 Visit 00, Screening Clinic Visit (Optional) (Day -28 to -1) .........................66 
8.1.2 Visit 01 Day 01, Enrollment (for subjects previously screened at Day -28 to 
-1) and First Vaccination (Dose 1), Clinic Visit ...........................................67 
8.1.3 Visit 01, Day 1, Enrollment/Baseline (for subjects not previously screened 
at Day -28 to -1) and First Study Vaccination (Dose 1), Clinic Visit ...........69 
8.2 
Follow-up Visits........................................................................................................71 
8.2.1 Visit 02, Day 4, Memory Aid Review, Phone Call ......................................71 
8.2.2 Visit 03, Day 8, Clinic Visit..........................................................................71 
8.2.3 Visit 04, Day 22, Second Study Vaccination (Dose 2), Clinic Visit ............72 
8.2.4 Visit 05, Day 25, Memory Aid Review, Phone Call ....................................74 
8.2.5 Visit 06, Day 29, Clinic Visit........................................................................75 
8.2.6 Visit 07, Day 43, Clinic Visit........................................................................75 
8.2.7 Visit 08, Day 82, Safety Follow-up, Phone Call...........................................76 
8.2.8 Visit 09, Day 142, Safety Follow-up, Phone Call.........................................77 
8.2.9 Visit 10, Day 202, Safety Follow-up, Clinic Visit ........................................77 
8.2.10 Visit 11, Day 387, Safety Follow-up, Phone Call.........................................78 
8.2.11 Early Termination Visit (if needed) ..............................................................78 
8.2.12 Unscheduled Visit (if needed) ......................................................................79 
9 
Assessment of Safety ............................................................................................................81 


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9.1 
Specification of Safety Parameters ...........................................................................81 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 81 
9.2.1 Adverse Events .............................................................................................81 
9.2.2 Reactogenicity...............................................................................................83 
9.2.3 Additional Adverse Event Severity Grading ................................................85 
9.2.4 Serious Adverse Events ................................................................................88 
9.2.5 Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings .........................................................89 
9.3 
Reporting Procedures ................................................................................................90 
9.3.1 Serious Adverse Events ................................................................................90 
9.3.2 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND
.......................................................................................................................91 
9.3.3 Reporting of Pregnancy ................................................................................91 
9.4 
Type and Duration of Follow-up of Subjects after Adverse Events .........................91 
9.5 
Halting Rules ............................................................................................................92 
9.6 
Safety Oversight........................................................................................................93 
9.6.1 Independent Safety Monitor (ISM) ...............................................................93 
9.6.2 Data and Safety Monitoring Board (DSMB) ................................................94 
10 
Clinical Monitoring ...............................................................................................................96 
10.1 
Site Monitoring Plan .................................................................................................96 
11 
Statistical Considerations ......................................................................................................97 
11.1 
Introduction ...............................................................................................................97 
11.2 
Study Hypotheses......................................................................................................97 
11.3 
Study Outcome Measures .........................................................................................97 
11.4 
Sample Size Considerations ......................................................................................97 
11.4.1 Study Population ...........................................................................................97 
11.4.2 Subject Enrollment and Follow-up ...............................................................98 
11.4.3 Sample Size ...................................................................................................98 
11.5 
Planned Interim Analyses .......................................................................................101 
11.5.1 Interim Safety Review ................................................................................101 
11.5.2 Interim Immunogenicity Review ................................................................102 
11.6 
Final Analysis Plan .................................................................................................103 
11.6.1 Analysis Populations ...................................................................................103 
11.6.2 Safety Data ..................................................................................................104 
11.6.3 Immunogenicity Data..................................................................................105 
11.6.4 Missing Values and Outliers .......................................................................106 
12 
Data Collection Forms and Access to Source Data/Documents .........................................107 
13 
Quality Control and Quality Assurance ..............................................................................108 
14 
Ethics/Protection of Human Subjects .................................................................................109 
14.1 
Ethical Standard ......................................................................................................109 


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14.2 
Institutional Review Board .....................................................................................109 
14.3 
Informed Consent Process ......................................................................................109 
14.3.1 Informed Consent........................................................................................109 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) ..................110 
14.5 
Subject Confidentiality ...........................................................................................111 
14.6 
Study Discontinuation .............................................................................................112 
14.7 
Costs, Subject Compensation, and Research Related Injuries ................................112 
14.8 
Future Use of Stored Specimens .............................................................................113 
15 
Data Handling and Record Keeping ...................................................................................115 
15.1 
Data Management Responsibilities.........................................................................115 
15.2 
Data Capture Methods ............................................................................................115 
15.3 
Types of Data ..........................................................................................................116 
15.4 
Timing/Reports .......................................................................................................116 
15.5 
Study Records Retention.........................................................................................117 
16 
Protocol Deviations .............................................................................................................118 
17 
Publication Policy ...............................................................................................................119 
18 
Literature References ..........................................................................................................120 
APPENDICES .............................................................................................................................125 
Appendix A. 
SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS .........126 
Appendix B. 
LIST OF POTENTIALLY IMMUNE-MEDIATED MEDICAL 
CONDITIONS ..........................................................................................................................
 
130 
 
 


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LIST OF TABLES 
Table 1: Study Design ....................................................................................................................xx 
Table 2: Venipuncture Volumes (mL): ..........................................................................................64 
Table 3: Power (%) to Detect Safety Events: ................................................................................99 
Table 4: Precision of Binomial Confidence Intervals: ...................................................................99 
Table 5: Minimum Detectable Difference in Proportion Responders with 80% Power..............100 
Table 6: Lower Confidence bound2 for difference in proportion of responders  between 
Adjuvanted (N = 100) and unadjuvanted (N = 50) arms, 19-64 years stratum ........100 
Table 7: Lower Confidence bound2 for difference in proportion of responders  between 
Adjuvanted (N = 50) and unadjuvanted (N = 25) arms, ≥65 years stratum .............100 
 


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LIST OF FIGURES 
Figure 1: Schematic of Study Design .......................................................................................... xxi 
 


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LIST OF ABBREVIATIONS 
A/H1N1 
Influenza A Virus of the H1N1 Subtype 
A/H2N2 
Influenza A Virus of the H2N2 Subtype 
A/H3N2 
Influenza A Virus of the H3N2 Subtype 
A/H3N2v 
Influenza A Virus of the H3N2 Variant Subtype 
A/H5N1 
Influenza A Virus of the H5N1 Subtype 
A/H5N2 
Influenza A Virus of the H5N2 Subtype 
A/H5N3 
Influenza A Virus of the H5N3 Subtype 
A/H5N6 
Influenza A Virus of the H5N6 Subtype 
A/H5N8 
Influenza A Virus of the H5N8 Subtype 
A/H7N1 
Influenza A Virus of the H7N1 Subtype 
A/H7N7 
Influenza A Virus of the H7N7 Subtype 
A/H7N9 
Influenza A Virus of the H7N9 Subtype 
A/H9N2 
Influenza A Virus of the H9N2 Subtype 
AS03 
Adjuvant System 03 
AdvantageEDCSM 
Electronic Data Capture System 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine Aminotransferase 
BARDA 
Biomedical Advanced Research and Development Authority 
BLA 
Biologics License Applications 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BPM 
Beats Per Minute 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CHMP 
Committee for Medicinal Products for Human Use 
CI 
Confidence Interval 
CMS 
Clinical Materials Services 
Cr 
Creatinine 
CSL 
Commonwealth Serum Laboratories 
CSR 
Clinical Study Report 
CVV 
Candidate Vaccine Virus 
°C 
Degrees Celsius 
°F 
Degrees Fahrenheit 
D 
Day(s) 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, NIH 
DSMB 
Data and Safety Monitoring Board 


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eCRF 
Electronic Case Report Form 
EIA 
Enzyme Immunoassay 
ELISpot 
Enzyme-Linked Immunosorbent Spot  
ESR 
Erythrocyte Sedimentation Rate 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
FWA 
Federalwide Assurance 
g/dL 
Grams per Deciliter 
GBS 
Guillain-Barré Syndrome 
GCP 
Good Clinical Practice 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline Biologicals 
HA 
Hemagglutinin 
HAI 
Hemagglutination Inhibition 
Hgb 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HPAI 
Highly Pathogenic Avian Influenza 
HPLC 
High-Performance Liquid Chromatography 
HRSA 
Health Resources and Services Administration 
IATA 
International Air Transport Association 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IgG 
Immunoglobulin G 
IGHV 
Immunoglobulin G Heavy Chain Variable 
IIV 
Inactivated Influenza Virus Vaccine 
IIV3 
Trivalent Inactivated Influenza Vaccine 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IU/L 
International Unit(s) per Liter 
mcg  
Microgram(s) 
µL 
Microliter(s) 
MAAEs 
Medically-Attended Adverse Events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF59 
MF59C.1 Adjuvant 
mg/dL 
Milligram(s) per Deciliter 


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mITT 
Modified Intent-to-Treat 
mL 
Milliliter(s) 
mm 
Millimeter(s) 
mmHg 
Millimeters of Mercury 
MOP 
Manual of Procedures 
N 
Number of Subjects 
NA 
Neuraminidase 
Neut 
Neutralizing or Neutralization 
NIAID 
National Institute of Allergy and Infectious Diseases, NIH, 
DHHS 
NIH 
National Institutes of Health 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
NOCMCs 
New-Onset Chronic Medical Conditions 
NVD 
Novartis Vaccines and Diagnostics 
OER 
Office of Extramural Research 
OHRP 
Office for Human Research Protections 
PBS 
Phosphate Buffered Saline 
PCR 
Polymerase Chain Reaction 
PHI 
Personal Health Information 
PIMMCs 
Potentially Immune-Mediated Medical Conditions 
PLT 
Platelets 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SDCC 
Statistical and Data Coordinating Center 
SDS-PAGE 
Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SRID 
Single Radial Immunodiffusion 
T. Bili 
Total Bilirubin 
TBD 
To Be Determined 
TGA 
Therapeutics Goods Administration 
UK 
United Kingdom 
US 
United States 
USDA 
US Department of Agriculture 
V 
Visit(s) 
VTEU 
Vaccine and Treatment Evaluation Unit 


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WBC 
White Blood Cells 
WHO 
World Health Organization 


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PROTOCOL SUMMARY 
Title: 
A Phase II Study in Healthy Adults 19 Years and Older to Assess 
the Safety, Reactogenicity and Immunogenicity of a Sanofi 
Pasteur A/H7N9 Inactivated Influenza Vaccine Administered 
Intramuscularly With or Without AS03 Adjuvant  
Phase: 
II 
Population: 
Approximately 400 (up to 420) individuals 19-64 years old, and 
approximately 240 (up to 300) individuals greater than or equal to 
(≥) 65 years old who have no history of influenza A/H7N9 
infection or prior receipt of an influenza virus H7 subtype vaccine. 
Number of Sites: 
Up to 9 Vaccine and Treatment Evaluation Unit (VTEU) sites 
Study Duration: 
Approximately sixteen (16) months 
Subject Participation 
Duration: 
Approximately thirteen (13) months 
Estimated Time to Complete 
Enrollment: 
Approximately 12 weeks 
Description of Agent: 
Two doses delivered intramuscularly (IM) approximately 21 days 
apart of a monovalent inactivated pre-pandemic influenza A/H7N9 
vaccine (2017 H7N9 IIV) manufactured by Sanofi Pasteur, at 
different dosages administered with AS03 adjuvant 
(GlaxoSmithKline Biologicals (GSK)) and Phosphate Buffered 
Saline (PBS) diluent (3.75 micrograms/0.5mL of hemagglutinin 
(HA)  from A/Hong Kong/125/2017 H7N9 vaccine per dose), or at 
dosages administered with AS03 adjuvant (GlaxoSmithKline 
Biologicals (GSK)) (7.5 and 15 micrograms /0.5mL of 
hemagglutinin (HA) from A/Hong Kong/125/2017 H7N9 vaccine 
per dose) or without adjuvant (15 mcg HA and 45 mcg HA per 
dose). 
Study Objectives: 
 
Primary: 
Safety: 
• To assess the safety and reactogenicity following receipt of 
two doses of 2017 H7N9 IIV administered intramuscularly 
at different dosages approximately 21 days apart given 
with or without AS03 adjuvant  
Immunogenicity: 


DMID Protocol 17-0075 
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• To assess the serum hemagglutination inhibition (HAI) and 
neutralizing (Neut) antibody responses following receipt of 
two doses of 2017 H7N9 IIV administered intramuscularly 
at different dosages approximately 21 days apart with or 
without AS03 adjuvant, stratified by age of recipient. 
Secondary: 
Safety: 
• To assess unsolicited non-serious adverse events (AEs) 
following receipt of two doses of a 2017 H7N9 IIV 
administered IM at different dosages approximately 21 
days apart with or without AS03 adjuvant  
• To assess medically-attended adverse events (MAAEs) 
including new-onset chronic medical conditions 
(NOCMCs), potentially immune-mediated medical 
conditions (PIMMCs), and all serious adverse events 
(SAEs) following receipt of two doses of a 2017 H7N9 IIV 
administered IM at different dosages approximately 21 
days apart with or without AS03 adjuvant 
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses 
approximately 7 and 21 days following receipt of a single 
dose, and approximately 7 days following receipt of two 
doses of 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without AS03 
adjuvant, stratified by age of recipient. 
Exploratory: 
Immunogenicity: 
• To assess the effects of age, sex, body mass index, and 
prior receipt of seasonal influenza vaccine(s) on serum 
HAI and Neut antibody responses following receipt of two 
doses of a 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without AS03 
adjuvant. 
• To assess, in at least a subset of samples, the cross-
reactivity of serum HAI and Neut antibody responses to 


DMID Protocol 17-0075 
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xv 
antigenically drifted variants of influenza A/H7 viruses 
following receipt of two doses of a 2017 H7N9 IIV 
administered intramuscularly at different dosages 
approximately 21 days apart with or without AS03 
adjuvant, stratified by age of recipient.  
• To assess the durability of serum HAI and Neut antibody 
responses at approximately 180 days following receipt of 
two doses of 2017 H7N9 IIV administered intramuscularly 
at different dosages approximately 21 days apart with or 
without AS03 adjuvant, stratified by age of recipient.  
• To assess the neuraminidase (NA) content of the 2017 
H7N9 IIV and determine the serum antibody responses to 
NA following receipt of 2017 H7N9 IIV. 
Study Outcome Measures: 
 
Primary: 
Safety: 
• 
Occurrence of study vaccine-related serious adverse events 
(SAEs) from the time of the first study vaccination through 
approximately 12 months after the last study vaccination. 
• 
Occurrence of solicited injection site and systemic 
reactogenicity events from the time of each study 
vaccination through 7 days after each study vaccination. 
• 
Occurrence of clinical safety laboratory adverse events 
from the time of each study vaccination through 
approximately 7 days after each study vaccination. 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving seroconversion against the influenza 2017 H7N9 
study vaccine strain (defined as either a pre-vaccination 
titer <1:10 and a post-vaccination titer ≥1:40 or a pre-
vaccination titer ≥1:10 and a minimum four-fold rise in 
post-vaccination antibody titer) at approximately 21 days 
after the second study vaccination (Study Day 43). 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving titer ≥1:40 against the influenza 2017 H7N9 


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study vaccine strain at approximately 21 days after the 
second study vaccination (Study Day 43). 
• 
Geometric Mean Titers (GMTs) of serum HAI and Neut 
antibodies against the influenza 2017 H7N9 vaccine strain 
at approximately 21 days after the second study 
vaccination (Study Day 43). 
Secondary: 
Safety: 
• 
Occurrence of study vaccine-related unsolicited non-
serious AEs from the time of each study vaccination 
through approximately 21 days after each study 
vaccination. 
• 
Occurrence of all unsolicited adverse events, regardless of 
the assessment of seriousness or relatedness, from the time 
of each study vaccination through approximately 21 days 
after each study vaccination.  
• 
Occurrence of MAAEs, including NOCMCs, and PIMMCs 
from the time of the first study vaccination through 
approximately 12 months after the last study vaccination. 
• 
Occurrence of all serious adverse events (SAEs), 
regardless of the assessment of relatedness, from the time 
of the first vaccination through approximately 12 months 
after the last study vaccination. 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving seroconversion against the influenza 2017 H7N9 
vaccine strain at approximately 7, 21, and 28 days after the 
first study vaccination (Study Days 8, 22, 29). 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving antibody titers of 1:40 or greater against the 
influenza 2017 H7N9 vaccine strain at baseline and 
approximately 7, 21, and 28 days after the first study 
vaccination (Study Days 8, 22, 29). 


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• 
GMTs of serum HAI and Neut antibodies against the 
influenza 2017 H7N9 vaccine virus at baseline and 
approximately 7, 21, and 28 days after the first study 
vaccination (Study Days 8, 22, 29). 
Exploratory: 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving seroconversion and the Geometric Mean Titers 
of serum HAI antibody against the 2017 H7N9 study 
vaccine strain approximately 21 and 180 days after the 
second study vaccination (Study Days 43 and 202), 
stratified by age, sex, body mass index, and prior receipt of 
seasonal influenza vaccine(s). 
• 
For HAI and Neut antibodies, for at least a subset of 
subjects, percentage achieving seroconversion, percentage 
with titer ≥1:40, and Geometric Mean Titers against 
antigenically drifted variants of influenza A/H7 viruses at 
baseline and approximately 21 and 180 days after the 
second study vaccination (Study Day 43 and 202). 
• 
For HAI and Neut antibodies, percentage of subjects 
achieving seroconversion, percentage with titer ≥1:40, and 
Geometric Mean Titers against the 2017 H7N9 study 
vaccine strain at approximately 180 days after the second 
study vaccination (Study Day 202). 
 
• 
Percentage of subjects with detectable levels of serum N9 
NA specific antibody elicited by 2017 H7N9 vaccination, 
and the correlation of the NA content of 2017 H7N9 IIV 
with the elicited NA specific antibody responses at 
baseline and approximately 8 and 21 days after the first 
study vaccination (Study Day 1, 9 and 21) and 8, 21 and 
180 days after the second study vaccination (Study Day, 
29, 43 and 202). 
 
Description of Study Design: This is a randomized, double-blinded, Phase II study in males and 
non-pregnant females, who are in good health, aged 19 years and 
older. This clinical trial is designed to assess the safety, 
reactogenicity, and immunogenicity of a pre-pandemic 2017 
monovalent inactivated influenza A/H7N9 virus vaccine (2017 


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H7N9 IIV),), manufactured by Sanofi Pasteur, administered at 
different dosages given 1) with AS03 adjuvant and Phosphate 
Buffered Saline (PBS) diluent [manufactured by GlaxoSmithKline 
(GSK) and Sanofi Pasteur, respectively], (3.75 mcg of HA per 
dose), 2) with AS03 adjuvant       (7.5 mcg and 15 mcg of HA per 
dose), or 3)   without adjuvant (15 mcg and 45 mcg of HA per 
dose). The 2017 H7N9 IIV was manufactured using a reverse 
genetics-derived reassortant candidate vaccine virus IDCDC 
RG56B (H7N9), containing the HA and NA from low pathogenic 
influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, 
NP, M and NS from A/Puerto Rico/8/1934 (H1N1). 
 
Subjects who are in good health and meet all eligibility criteria 
(including an erythrocyte sedimentation rate [ESR], urine or serum 
pregnancy test, history and physical exam) within 28 days prior to 
the first vaccination or on the day of, but prior to, first vaccination, 
will be randomized into one of five study groups, stratified by age 
as shown in Table 1. Baseline clinical safety laboratories will be 
drawn prior to the first vaccine dose and will not be used to screen 
subjects for eligibility. 
Reactogenicity will be measured by the occurrence of solicited 
injection site and systemic reactions from the time of each study 
vaccination through 7 days after each study vaccination. 
Unsolicited non-serious AEs will be collected from the time of 
each study vaccination through approximately 21 days after each 
study vaccination. SAEs, MAAEs, including NOCMCs, and 
PIMMCs, will be collected from the time of the first study 
vaccination through approximately 12 months after the last study 
vaccination. Clinical laboratory evaluations for safety will be 
performed on venous blood collected prior to each study 
vaccination and approximately 7 days after each study 
vaccination. 
Immunogenicity testing will include performing HAI and Neut 
antibody assays against the 2017 H7N9 vaccine virus on serum 
samples obtained immediately prior to each study vaccination 
(Days 1 and approximately Day 22), approximately 7 days after 


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each study vaccination (Days 8 and 29), and approximately 21 and 
180 days after the second study vaccination (Days 43 and 202). 
Novel methods for identifying and assessing alternative correlates 
of protection against influenza infection are needed.  To assess the 
NA specific antibody response to vaccination, it is first necessary 
to determine the NA content of inactivated influenza vaccine; this 
assay is under development.  If successful, the NA content in a 
dosage specific manner can be correlated to the N9 NA-specific 
antibody responses elicited by the 2017 H7N9 IIV. 
Subjects who have not received licensed 2017-2018 seasonal 
trivalent or quadrivalent inactivated influenza vaccine (IIV3 or 
IIV4, including high dose vaccine for the elderly) prior to 
enrollment may receive it anytime following completion of the 
Day 43 study visit or upon early termination. 


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Table 1: Study Design 
Treatment Arms 
Stratum 
Day 1 
Day 22 
Group 1, n=160 
Age 19-64, n=100 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent plus GSK AS03 
adjuvant 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/PBS 
diluent plus GSK AS03 
adjuvant 
Age ≥ 65, n=60 
Group 2, n=160 
Age 19-64, n=100 
Sanofi Pasteur H7N9 
vaccine 7.5 mcg plus GSK 
AS03 adjuvant 
Sanofi Pasteur H7N9 
vaccine 7.5 mcg plus GSK 
AS03 adjuvant 
Age ≥ 65, n=60 
Group 3, n=160 
Age 19-64, n=100 
Sanofi Pasteur H7N9 
vaccine 15 mcg plus GSK 
AS03 adjuvant 
Sanofi Pasteur H7N9 
vaccine 15 mcg plus GSK 
AS03 adjuvant 
Age ≥ 65, n=60 
Group 4, n=80 
Age 19-64, =50 
Sanofi Pasteur H7N9 
vaccine 15 mcg 
unadjuvanted 
Sanofi Pasteur H7N9 
vaccine 15 mcg 
unadjuvanted 
Age ≥ 65, n=30 
Group 5, n=80 
Age 19-64, n=50 
Sanofi Pasteur H7N9 
vaccine 45 mcg 
unadjuvanted 
Sanofi Pasteur H7N9 
vaccine 45 mcg 
unadjuvanted 
Age ≥ 65, n=30 
Total Enrollment, 
n = 640 
Age 19-64, n=400* 
*Over enrollment up to 420 subjects may be allowed to 
ensure approximately 100 subjects in each AS03 
adjuvanted treatment arm, and 50 subjects in each of the 
unadjuvanted treatment arm are eligible for inclusion in 
post Dose 2 immunogenicity analyses 
Age ≥ 65, n=240** 
**Over enrollment up to 300 subjects may be allowed to 
ensure 60 subjects in each of the AS03 adjuvanted 
treatment arms, and 30 subjects in each of the 
unadjuvanted treatment arms are eligible for inclusion in 
post Dose 2 immunogenicity analyses 
 


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Figure 1: Schematic of Study Design 
 
 
≥ 65 Years Old 
(N = 240) 
Randomize 2:2:2:1:1 
Planned Enrollment: Total N=640 Subjects* 
 
*The study is planned to enroll a minimum of 640 subjects with a target of (n=160 in each treatment 
arm with AS03 adjuvant, (100 in the subjects 19-64 years old, 60 in the subjects ≥ 65 years old)) and 
(n=80 in each treatment arm with no adjuvant, (50 in the subjects 19-64 years old, 30 in the subjects ≥ 
65 years old)), but may continue enrollment up to a maximum of 420 subjects in the 19-64 years old 
age stratum and 300 subjects in the ≥65 years old age stratum. 
Administer Study Vaccine per Subject Treatment 
Assignments on Day 1 and approximately Day 22 
Assessment of 
Final Outcome 
Measures 
Consent 
 
Assess Eligibility 
19-64 Years Old 
(N = 400) 
Randomize 2:2:2:1:1 
Clinical, Safety, Reactogenicity, and 
Immunogenicity Assessments 


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1 
KEY ROLES 
Lead Principal Investigator: 
 
Lisa A. Jackson, MD, MPH 
Kaiser Permanente Washington Health Research Institute 
 
DMID Clinical Project Manager: 
Robin M. Mason, MS 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
 
DMID Medical Monitor: 
Mohamed Elsafy, MD 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
 
DMID Medical Officer: 
 
Francisco J. Leyva MD, PhD, ScM 
Division of Microbiology and Infectious Diseases 
NIAID, NIH  
 
DMID Scientific Lead: 
 
Chris Roberts, Ph.D. 
Division of Microbiology and Infectious Diseases 
NIAID/NIH/DHHS 
 
Safety and Pharmacovigilance 
Contractor: 
 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support 
(CROMS) 
 
 
 
 
Site Principal Investigators: 
Lisa A. Jackson, MD, MPH 
Kaiser Permanente Washington Health Research Institute 
Kaiser Permanente 
 
Jack Stapleton, MD  
Depts. of Internal Medicine & Microbiology and Immunology 
University of Iowa 
 
Wilbur Chen, MD 
University of Maryland 
 
 


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Emmanuel “Chip” Walter, MD, MPH 
Duke University School of Medicine 
 
Evan J. Anderson, MD 
Emory University School of Medicine 
 
Nadine Rouphael, MD 
Emory University School of Medicine 
 
Statistical and Data Coordinating 
Center: 
The Emmes Corporation 
 
Clinical Materials Services: 
Fisher BioServices 
 
HAI and Neut Antibody Assays 
Laboratory: 
Southern Research 
 


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2 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 
Background Information 
The continued emergence of novel influenza A viruses in humans including subtypes H5N1, 
H3N2v, H7N7, H9N2, 2009 H1N1, and most recently H5N6 and H7N9, underscores the need 
for focused efforts to prepare for the next influenza pandemic [1-6]. Four pandemics occurred 
during the last century. It was estimated that during the 1918 influenza A/H1N1 pandemic as 
many as 40 million deaths occurred worldwide [7]. Excess mortality, high morbidity, and social 
disruption were all noted during the 1957 influenza A/H2N2 and the 1968 influenza A/H3N2 
pandemics [8]. In April 2009, a novel influenza virus (2009 A/H1N1) originated in pigs and 
spread to humans around the world becoming the first pandemic of this century. In each of these 
influenza pandemics, human populations lacked significant levels of pre-existing immunity to a 
highly transmissible form of the virus enabling it to spread rapidly. Thus, each emergence of a 
new strain of influenza virus in the human population has the potential to result in a global public 
health emergency. 
A major cornerstone of pandemic preparedness is the capacity to rapidly produce and deliver 
sufficient quantities of safe and effective strain-specific pandemic influenza vaccines. The threat 
of pandemic influenza in 1976 (swine influenza) and again in 1977 (Russian influenza) resulted 
in inactivated influenza virus vaccine (IIV) development programs that provided important 
insights into variables influencing the immune responses to immunization [9, 10]. Vaccine- 
associated factors potentially affecting the immunogenicity of IIVs that were noted during the 
1976 experience and have been refined in subsequent years include the amount of viral 
hemagglutinin (HA) protein in the vaccine, the number and intervals of doses administered, the 
addition of immune stimulating components (i.e., adjuvants), and the manufacturing methods 
used to produce the vaccine (i.e., whole virus, split virus, or purified surface antigen). Host-
specific factors, including the recipient’s age, their prior influenza infections and/or vaccinations, 
and the presence of underlying diseases and their treatments, all can influence the immune 
responses elicited by an influenza vaccine. 
Serum antibodies targeting the influenza virus HA and neuraminidase (NA), the major surface 
glycoproteins on influenza viruses, play a key role in protective immunity to influenza virus 
infection [11]. Since protection against infection with seasonal influenza virus strains has been 
shown to correlate with both serum hemagglutination inhibition (HAI) and neutralizing (Neut) 
antibody levels, their measurements are used routinely to assess the immunogenicity of both 
seasonal and pandemic IIVs. Recent data also supports an important role for neuraminidase 
inhibiting (NI) antibodies in protection against disease [12]. In a recent human influenza 


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challenge study, serum NI antibody levels were also identified as an independent correlate of 
protection against influenza illness [13].  In the current study, we plan to assess the NA content 
of 2017 H7N9 IIV and determine the correlation of NA content at different vaccine dosages with 
the elicited humoral antibody responses to the NA. 
Several approaches have been used to increase the immunogenicity of IIVs. Standard-dose 
inactivated seasonal influenza vaccines contain 7.5 mcg of HA antigen per vaccine strain (for 
children aged <36 months) or 15 mcg of HA antigen per vaccine strain (for persons aged ≥36 
months). Clinical studies evaluating increased HA-containing influenza vaccines performed over 
the past 35 years have shown dose-related increases in serum and mucosal antibody responses 
[14-22]. Higher HA dosage vaccines can lead to enhanced antibody responses in the elderly [23]. 
In 2009, a high-dose IIV containing 4 times the standard HA antigen per seasonal vaccine strain 
was approved in the United States (US) for use in individuals 65 years of age and older.  
In general, clinical studies evaluating vaccines made from novel avian influenza viruses (e.g., 
A/H5N1, A/H7N7) suggest that these vaccines are substantially less immunogenic than those 
from other novel subtypes (e.g., 2009 A/H1N1 pandemic virus, even when administered at high 
HA dosages [24, 25]). Due to the poor immunogenicity of H5 and H7 vaccines, the inclusion of 
adjuvants was evaluated to assess their ability to boost anti-viral serum IgG levels. In the United 
States, aluminum salts are licensed as adjuvants in combination with several vaccines; however, 
their use in subvirion influenza A/H5N1 vaccines has shown either no effect or a very modest 
enhancement of immune responses compared to non-aluminum salt containing formulations [26-
28]. In contrast, the use of oil-in-water emulsion adjuvants, most notably proprietary adjuvants 
AS03 and MF59 produced by GlaxoSmithKline Biologicals (GSK) and Seqirus, respectively, 
has resulted in increased antibody responses to IIVs containing novel HAs in numerous clinical 
trials [29-33]. In an early study, dosage levels ranging from 3.75 to 30 mcg of A/H5N1 antigen 
administered with or without AS03 resulted in significant increases in antibody Geometric Mean 
Titers (GMTs) in groups who received the adjuvanted formulations [31]. These GMTs met the 
Committee for Medicinal Products for Human Use (CHMP) criterion for seroconversion rate 
(>40%) after a single dose with adjuvant. Following the second vaccine dose, all adjuvanted 
formulations complied with both CHMP and US Food and Drug Administration (FDA) criteria 
for seroconversion and seroprotection rates, whereas from the non-adjuvanted groups only the 30 
mcg formulation met the CHMP criterion for seroconversion [31]. GSK received approval for 
the registration of a pre-pandemic AS03-adjuvanted, monovalent inactivated A/H5N1 virus 
vaccine by European regulatory authorities in 2008 and FDA approval of their Biologics License 
Applications (BLA) for an Influenza A (H5N1) Virus Monovalent Vaccine Adjuvanted (with 
AS03) in 2013. 
Following the 2009 emergence of the novel A/H1N1 pandemic virus, the European Commission 
granted marketing authorization of GSK’s egg-derived AS03-adjuvanted monovalent inactivated 


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2009 A/H1N1 virus vaccine (Pandemrix™) and Novartis’ egg-derived MF59-adjuvanted, 
monovalent inactivated 2009 A/H1N1 virus vaccine (FOCETRIATM). These adjuvanted 
monovalent inactivated 2009 A/H1N1 virus vaccines were widely used throughout Europe and in 
many other countries, albeit not in the US. 
The inclusion of adjuvants in clinical trials evaluating IIVs has also frequently been associated 
with increased injection site reactogenicity [26]. Additionally, in late 2010, a possible association 
between an increased risk of narcolepsy in children and adolescents who had received the AS03-
containing Pandemrix™ was reported in Finland and Sweden. Some, but not all, countries in 
which retrospective studies were conducted showed a similar association [34-43]. (See also 
Section 2.3.1 Potential Risks for further discussion). 
Because of the substantial increases in antibody responses when these oil-in-water emulsion 
adjuvants were added to otherwise poorly immunogenic, novel HA influenza vaccines, they may 
be a critical component of the public health response to the next influenza pandemic. As part of 
its pandemic preparedness efforts, the US Government maintains stockpiles of unique HA-
containing influenza vaccines, including those against influenza A/H7N9 and A/H5N1 viruses, 
as well as AS03 and MF59 adjuvants. The National Institute of Allergy and Infectious Diseases 
(NIAID) has conducted several clinical trials to evaluate A/H7N9 and A/H5N1 vaccines 
administered with and without these adjuvants in healthy adult and elderly populations and found 
that the vaccines co-administered with adjuvants were well tolerated, exhibited dose-sparing and 
substantially increased the immunogenicity of strain-specific novel HA vaccines compared to 
non-adjuvanted formulations [44-49]. In response to emerging H5N8 viruses that have caused 
extensive outbreaks in domestic poultry and wild birds in South East Asia [50, 51], NIAID is 
also conducting 2 ongoing clinical trials with an H5N8 vaccine produced by bioCSL (Seqirus) 
administered with either AS03 (GSK) or MF59 (Seqirus) in healthy individuals 19-64 years of 
age (NCT02624219 and NCT03014310). 
Since March of 2013 [52], avian influenza A/H7N9 viruses have continued to circulate in China 
causing discrete outbreaks (or waves) in humans with high mortality over the past 5 years. By 
late 2016, a “fifth wave” of outbreaks was identified in China and as of December 7, 2017 a total 
of 1,565 laboratory-confirmed human infections with avian influenza A/H7N9 virus have been 
reported by the World Health Organization [53, 54]. Whereas most cases have been centered in 
and around mainland China, there have been several traveler associated cases, including two in 
travelers reported by Canada who were returning from China in early 2015 [55]. Most of the 
reported human cases have been associated with exposure to infected live poultry or 
contaminated environments, including markets where live poultry are sold. Influenza A/H7N9 
viruses continue to be detected in poultry and their environments in the areas where human cases 
are occurring. Information to date indicates that these viruses do not transmit easily from human 
to human with most isolates appearing to have retained their susceptibility to NA inhibitors [53]. 


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Laboratory studies have shown that A/H7N9 influenza viruses readily infect cells from human 
respiratory tract tissue samples and can spread from ferret to ferret by droplet transmission, 
thereby increasing the concern about the pandemic potential of these viruses [56, 57]. 
Since the onset of the “fifth wave” of H7N9 outbreaks in October 2016, more human cases of 
H7N9 infection have been reported in China than any prior H7N9 epidemic wave [54]. In 
addition, an antigenically distinct lineage of these fifth wave H7N9 viruses known as the 
Yangtze River Delta lineage, has recently emerged and has been associated with an increasing 
number of human cases. This lineage has also resulted in a broader geographic spread of infected 
birds and human cases within China than previously seen. Further, several H7N9 viruses in the 
Yangtze River Delta lineage have recently acquired genetic changes characteristic of highly 
pathogenic avian influenza (HPAI) viruses and have now shown an increased ability to infect 
and kill poultry [53, 58].  
The U.S. Department of Health and Human Services (HHS) recently assessed H7N9 influenza 
virus as having a significant potential to cause a pandemic, and the greatest risk of causing 
severe disease. As a result, HHS has supported the production of fifth wave inactivated influenza 
H7N9 vaccine for the U.S. stockpile and for an assessment of its safety and immunogenicity in 
clinical trials. 
2.1.1 
Public Readiness and Emergency Preparedness Act 
For this protocol the study products monovalent inactivated influenza 2017 H7N9 virus vaccine 
manufactured by Sanofi Pasteur and adjuvant (AS03) manufactured by GSK, are covered under 
the Public Readiness and Emergency Preparedness Act (PREP Act). Under the PREP Act, 
covered persons are immune from liability actions brought from the administration or use of a 
covered countermeasure that is the subject of a declaration. The PREP Act provides immunity 
for covered persons (such as manufacturers, distributers, program planners, and other qualified 
persons who prescribe, administer, or dispense the 2017 H7N9 IIV with or without adjuvant) 
from tort liability, unless the injury was caused by willful misconduct. 
The PREP Act also established the Countermeasures Injury Compensation Program (CICP)to 
provide compensation for serious injuries that occur as the result of the administration or use of 
certain countermeasures. Any requests for compensation must be filed within one year of 
administration or use of the countermeasure. Requests would go to the Health Resources and 
Services Administration (HRSA) Preparedness Countermeasures Injury Compensation Program 
(http://www.hrsa.gov/cicp/). Compensation may then be available for medical benefits, lost 
wages, and death benefits to eligible individuals for specified injuries in accordance with 
regulations published by the Secretary of HRSA. Eligibility for compensation and the injuries for 
which compensation may be available are further defined by regulation. 


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An individual who suffers a serious physical injury or death from administration and use of the 
2017 H7N9 IIV with or without adjuvant may request benefits from the CICP. A serious physical 
injury means an injury that is life threatening, results in, or requires, medical or surgical 
intervention to prevent permanent impairment of a body function, or permanent damage to body 
structure. The CICP is the payer of last resort. This means that it only covers expenses or 
provides benefits that other third-party payers, such as health insurance, the Department of 
Veterans Affairs, or Workers’ Compensation programs don’t have an obligation to pay.  
If no funds have been appropriated to the compensation program, the Secretary of HRSA does 
not make a final determination on the individual’s request within 240 days, or if the individual 
decides not to accept the compensation, the injured individual or his representative may pursue a 
tort claim in the US District Court for the District of Columbia, but only if the claim involves 
willful misconduct, is pled with particularity required under the PREP Act, verified, and 
accompanied by an affidavit by a physician who did not treat the individual and certified medical 
records. Any award is reduced by any public or private insurance or worker’s compensation 
available to the injured individual. Awards for non-economic damages, such as pain, suffering, 
physical impairment, mental anguish, and loss of consortium are also limited. If the individual 
accepts compensation, or if there is no willful misconduct, then the individual does not have a 
tort claim that can be filed in a United States Federal or a State court. 
2.2 
Scientific Rationale 
As part of the US Government’s past pandemic preparedness efforts, Sanofi Pasteur under 
contract to the Biomedical Advanced Research and Development Authority 
(BARDA)/Department of Health and Human Services (DHHS), produced several novel pre-
pandemic vaccines that were evaluated by NIAID’s VTEU sites to assess their safety, 
reactogenicity, and immunogenicity when mixed prior to administration with either AS03 or 
MF59 oil-in-water adjuvants manufactured by GSK and Seqirus, respectively. In general, these 
trials have demonstrated that adjuvant use results in a significant dose-sparing effect. NIAID is 
currently conducting similar “mix and match” clinical trials using an H5N8 vaccine antigen 
produced by Seqirus and mixed with either AS03 or MF59 adjuvants (NCT03014310, 
NCT02624219). 
The large number of human infections starting with the “fifth wave” of H7N9 outbreaks in late 
2016, has raised the pandemic risk assessment of influenza A/H7N9 viruses circulating in China. 
The Yangtze River Delta lineage, a distinct H7N9 viral lineage, has now emerged and has been 
associated with many of the cases in the fifth epidemic wave. This has also resulted in a broader 
geographic spread of infected birds and human cases within China than previously reported. 
Further, several H7N9 viruses in the Yangtze River Delta lineage have recently acquired genetic 
changes characteristic of highly pathogenic avian influenza (HPAI) viruses and have now shown 


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an increased ability to infect and kill poultry [54, 58]. To date, no cases of H7N9 from the new 
lineage have been identified in birds or people infected outside of China; however, a few cases 
have been identified in Hong Kong and Taiwan in infected travelers returning from China. 
Importantly, antigenic analysis of the fifth wave H7N9 viruses and serology studies indicate that 
the stockpiled H7N9 vaccine manufactured several years ago does not induce protective HAI or 
Neut antibodies against the Yangtze River Delta lineage. Hence, there is broad consensus across 
HHS and interagency leadership that a new vaccine should be developed that would be effective 
against the currently predominating H7N9 viruses.  
Several candidate vaccine viruses are under evaluation by the CDC and the World Health 
Organization (WHO) H5 Reference Laboratories Network.  Under contract to BARDA/DHHS, 
Sanofi has produced a monovalent inactivated influenza pre-pandemic 2017 A/H7N9 virus 
vaccine (2017 H7N9 IIV) using largely the same manufacturing process as its licensed seasonal 
trivalent inactivated influenza virus vaccine. The availability of the US Government-stockpiled 
AS03 (GSK) oil-in-water adjuvant provides an opportunity to determine if dose-sparing effects 
occur when mixing the Sanofi 2017 H7N9 vaccine with the AS03 adjuvant (See Sections 2.3.1 
and 6.1 for additional details on the H7N9 vaccine). 
The goal of this clinical trial is to assess the safety, reactogenicity and immunogenicity of two 
doses of the 2017 H7N9 IIV administered with or without AS03 in healthy adult and the elderly 
individuals.  The 2017 H7N9 IIV manufactured by Sanofi will be mixed at the site with or 
without AS03 and will be administered IM at different dosages with AS03 [3.75, 7.5 and 15 mcg 
HA per dose (based on label content)] or without AS03 (15 or 45 mcg HA per dose) to evaluate 
the dose-sparing potential of the adjuvant. Data from phase I clinical trials of avian IIVs suggest 
that they are poorly immunogenic and require multiple high-doses or the inclusion of an adjuvant 
to induce serum HAI titer of 40 or greater against the study vaccine virus. In previous NIAID 
sponsored clinical trials of 2013 H7N9 IIV, 2 doses of non-adjuvanted 45 mcg of HA per dose 
did not confer significant seroprotection [46, 48].  However, to confirm the poor immunogenicity 
of the 2017 H7N9 IIV, a study arm with 2 high-doses (45 mcg HA per dose administered 
approximately 21 days apart) of non-adjuvanted 2017 H7N9 IIV is included in the study 
design.  The 45 mcg dosage represents a 12-, 6-, and 3-fold excess of vaccine antigen, 
respectively, over the 3.75 mcg, 7.5 mcg, and 15 mcg dose-sparing formulations achievable with 
the AS03 adjuvant. In addition to assessing antigen-sparing strategies, another goal of this study 
is to assess in at least a subset of samples, if serum IgG elicited by the 2017 H7N9 IIV recognize 
antigenically drifted variants of influenza A/H7 viruses. Since antibodies targeting the NA may 
represent an independent correlate of protection against influenza infection [11-13], we plan to 
assess the NA content of the 2017 H7N9 vaccine and determine if there is a dose-specific 
correlation of NA content with elicited humoral antibody responses to the N9 NA. 
Based on previously conducted studies with a 2013 H7N9 IIV manufactured by Sanofi Pasteur 
administered with or without AS03, we anticipate that two doses of the 2017 H7N9 IIV 


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administered IM at different dosages with AS03 adjuvant approximately 21 days apart will be 
well-tolerated and more immunogenic compared to the non-adjuvanted vaccine in healthy adult 
and elderly individuals. 
2.3 
Potential Risks and Benefits 
2.3.1 
Potential Risks 
The potential risks of participating in this trial are those associated with having blood drawn, the 
IM injection and possible reactions to the monovalent inactivated influenza H7N9 vaccine, with 
or without PBS diluent, and/or AS03 adjuvant, and breach of confidentiality. 
Drawing blood may cause transient discomfort and fainting. Fainting is usually transient and 
managed by having the subject lie down and elevate his/her legs. Bruising at the blood draw site 
may occur, but can be prevented or lessened by applying pressure to the blood draw site for a 
few minutes after the blood is taken. IM injection may also cause transient discomfort and 
fainting. Drawing blood and IM injection may cause infection. The use of aseptic (sterile) 
technique will make infection at the site where blood will be drawn or where the study 
vaccination will be given extremely unlikely. 
There is a small amount of risk to subjects who report that they are in good health but who have 
an unknown health problem at the time of screening. This trial will screen by physical exam, 
history, vital signs and sedimentation rate. Baseline safety labs for white blood cells (WBC), 
hemoglobin (Hgb), platelets (PLT), alanine aminotransferase (ALT), total bilirubin (T. Bili), and 
creatinine (Cr) will be drawn prior to study vaccination but results will not be reviewed until 
after study vaccination. To minimize the risk, subjects will not receive the second study 
vaccination unless, the most recently evaluated clinical safety laboratory values obtained prior to 
the second study vaccination are Grade 2 or less and the subject does not meet any of the other 
criteria listed in Section 5.2.3. 
There is potential for AEs to occur more frequently in the adjuvanted vaccine groups [59] than in 
the non-adjuvanted group and there is potentially a higher risk for AEs to occur more frequently 
in the higher dose influenza antigen groups than in the lower dose viral antigen groups. The 
monovalent A/H7N9 vaccine to be used in this study has not been tested for safety in animals 
and has not previously been evaluated in humans. The Division of Microbiology and Infectious 
Diseases (DMID), NIAID sponsored two Phase II clinical trials that included an assessment of 
the safety, reactogenicity, and immunogenicity of two IM doses of a monovalent A/H7N9 
vaccine produced by Sanofi Pasteur, Swiftwater, PA, administered with or without AS03 in 
healthy adults (DMID Protocol 13-0032; NCT01938742 and DMID Protocol 13-0033; 
NCT01942265).  


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Overall, the study products administered in both of these clinical trials were generally safe and 
well-tolerated. For DMID Protocol 13-0032, nine SAEs were reported. All were assessed as 
being not related to study product. Two AEs of special interest (AESIs) were reported in this 
clinical trial: Hashimoto’s disease (assessed as not related to study product) and Hashimoto’s 
thyroiditis (assessed as related to study product). For DMID Protocol 13-0033, sixteen SAEs 
were reported, fifteen of these SAEs were assessed as being not related to study product. One 
SAE was considered to be related: acute inferior myocardial infarction. Two AESIs were 
reported in this clinical trial: psoriasiform dermatitis and celiac disease (both assessed as not 
related to study product because both disorders pre-existed to vaccination, but both disorders 
received the diagnosis after vaccination). 
The current monovalent split IIV was derived from the influenza virus A/Hong Kong/125/2017 
(H7N9). The manufacturing process for the production of this investigational A/H7N9 vaccine 
is similar to the process used to produce the licensed Influenza Virus Vaccine Fluzone® family 
of products. As such, the safety profile of the candidate A/H7N9 vaccine should be similar to 
the current Fluzone® vaccine. 
 
 
 
 
 
 
 
 
 
  
The potential risks to subjects are anticipated to be similar to those observed for Sanofi Pasteur’s 
unadjuvanted licensed inter-pandemic (seasonal) IIVs (Fluzone® and Fluzone® High-Dose), their 
unadjuvanted licensed 2009 A/H1N1 and A/H5N1 monovalent IIVs, and for previously 
conducted 2013 H7N9 IIV administered with and without AS03 and MF59 (see the Sanofi 
Pasteur Investigator’s Brochure Investigational Pandemic Influenza Virus vaccines, Monovalent 
A/Shanghai/2/2013 (H7N9) product code 504, Monovalent A/Hong Kong/125/2017 (H7N9) 
product code 504, Monovalent A/Indonesia/05/2005 (H5N1) product code 458, Monovalent 
A/Vietnam/1203/2004 (H5N1) product code 399, Monovalent A/Bar-Headed Goose/Qinghai 
Lake/1A/2005 (H5N1) product code 458, Version Number 1.0, January 2018). 
Occasionally, adult recipients of unadjuvanted licensed, IIVs may develop influenza-like 
reactions, such as fever, feverishness (chills/shivering/sweating), fatigue (tiredness), malaise 
(general unwell feeling), myalgia (body aches/muscular pain), arthralgia (joint pain), headache, 
and/or nausea. Some subjects may develop reactions at the injection site, including pruritus 


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(itching), ecchymosis (bruising), erythema (redness), induration (hardness), swelling, pain, 
and/or tenderness. Most of these reactions peak in intensity in the first 24 hours after vaccination 
and disappear without treatment within 1 or 2 days. Analgesics (e.g., acetaminophen, ibuprofen, 
or similar non-steroidal anti-inflammatory drugs (NSAIDs)) and rest may generally relieve or 
lessen these reactions. Bruising can sometimes occur due to the vaccination procedure. 
In addition, post-marketing surveillance indicates autoimmune disorders as potential risks for 
pandemic vaccines based on those identified for the seasonal IIVs; these may also include, but 
are not limited to, neuritis, convulsions, severe allergic reactions, syncope, encephalitis, 
thrombocytopenia, vasculitis, and Guillain-Barré syndrome. Reports of these reactions were rare; 
however, exact incidence rates cannot be precisely calculated.  
Acute and potentially life-threatening allergic reactions (i.e., anaphylaxis) are also possible. 
These reactions occur in about 1 in 4 million people given a vaccination. These reactions can 
manifest as skin rash (hives), swelling around the mouth, throat, or eyes (angioedema), difficulty 
breathing (bronchospasm), a fast pulse (tachycardia), or decrease in blood pressure 
(hypotension). If these reactions occur, they can usually be stopped by the administration of 
emergency medications by the study personnel. As with any vaccine or medication, there is a 
very small chance of a death, although researchers do not expect this to occur. 
During the swine influenza (H1N1) vaccine campaign of 1976, some recipients developed a 
paralytic illness called Guillain-Barré syndrome (GBS). GBS is an acute inflammatory 
neuropathy characterized by weakness, hyporeflexia or areflexia, and elevated protein 
concentrations in cerebrospinal fluid. The rate of GBS was significantly increased in individuals 
receiving the 1976 swine influenza (H1N1) vaccine at about 1 per 100,000 vaccine recipients. 
This syndrome has not been seen consistently with other influenza vaccines. Most persons who 
develop GBS recover completely, although the recovery period may be as little as a few weeks 
or as long as a few years. About 30% of those with GBS still have residual weakness after 3 
years and about 3% may suffer a relapse of muscle weakness and tingling sensations many years 
after the initial attack. Intensive surveillance of GBS after administration of IIVs since 1976 has 
shown a slight increase in risk over background cases (more than one additional case of GBS per 
million persons) following vaccination, typically with onset within 6 weeks after vaccination 
[60]. Interestingly, although vaccination rates have increased in the last 10 years, the numbers of 
reported cases of vaccine-associated GBS have declined [61]. A recent study in Canada showed 
that the 2009 H1N1 vaccine was associated with a small but significant risk of GBS in persons 
50 years and older [62]. An active, population-based surveillance study conducted in the United 
States during the 2009-2010 influenza season found less than 1 excess GBS case per million 
doses of 2009 H1N1 vaccine administered – a rate similar to that associated with some 
previously administered annual influenza vaccines [63-65]. Another study using the Medicare 
system showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate 


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ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses 
administered, 95% confidence interval: 0.21, 5.48) [66]. An international collaboration study 
also supported a conclusion of an association between 2009 H1N1 vaccination and GBS [67]. It 
is unknown if the administration of the monovalent inactivated influenza 2017 H7N9 virus 
vaccine to be used in this clinical trial will result in an increased incidence of GBS as the 
mechanism leading to this AE has not been completely elucidated. 
As of November 22, 2015 (per the manufacturer’s IB dated February 2016), data are available 
for 56 GSK sponsored clinical trials of AS03-adjuvanted monovalent pandemic vaccines 
manufactured by GSK. More than 18,000 adult (age ≥18 years) and 6,900 pediatric (6 months to 
17 years old) clinical trial participants have received at least one dose of a GSK-manufactured, 
AS03-adjuvanted monovalent pandemic influenza vaccine. Clinical data collected by GSK as of 
November 22, 2015, suggest that inactivated monovalent (pre)pandemic influenza virus antigens 
adjuvanted with AS03 have generally acceptable safety and benefit/risk profiles, though the 
incidence rates of solicited local and systemic AEs are higher with AS03-adjuvanted antigens 
than with antigen alone, a licensed IIV3, or placebo. Some unsolicited AEs (e.g., insomnia, 
dizziness, cystitis) were associated with a higher relative risk among H5N1/AS03 recipients in 
contrast to Fluarix® or placebo recipients. 
The information and guidance that follow are based on pre-clinical and clinical study results for 
GSK-manufactured AS03-adjuvanted monovalent pandemic vaccines, post-marketing safety 
surveillance data seen with unadjuvanted, IIV3s and (in the case of the H1N1 vaccines) post-
marketing safety surveillance data seen to date for both Pandemrix™ and Arepanrix™ H1N1 
vaccines. 
The reactogenicity profile in humans of GSK-manufactured AS03-adjuvanted vaccines is 
primarily associated with the adjuvant. The incidence and severity of injection site redness, 
swelling, and pain at the injection site in recipients of AS03-adjuvanted vaccines are increased 
relative to monovalent pandemic influenza antigen alone, a licensed IIV3, or placebo. There is no 
increase in injection site and systemic reactogenicity events in recipients of AS03-adjuvanted 
vaccines after a second dose of vaccine relative to the first when given 21 days apart. In young 
children (6 months to 6 years old), increased frequency of fever has been observed following a 
heterologous booster dose of adjuvanted vaccine administered 6 months after the primary series. 
As of November 22, 2015, there has been no evidence in clinical trials to support a conclusion 
that any potential immune-mediated disease or group of diseases was causally related to an AS03-
adjuvanted vaccine. There have been no deaths in GSK clinical trials of AS03-adjuvanted 
pandemic influenza vaccines assessed as related to study vaccine. A total of 1,428 non-fatal SAEs 
have been reported for adult subjects as of November 22, 2015. Fifteen of these events were 
deemed related to vaccination by the Investigator or GSK. Of these, six occurred in recipients of 
an adjuvanted H1N1 vaccine: asthma, herpes zoster, hepatic enzyme increased, and pain in 


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extremity, polymyalgia rheumatic, and thrombocytopenia. Three occurred in recipients of 
unadjuvanted H1N1 vaccine: alanine aminotransferase increased, hypersensitivity, and multiple 
sclerosis. One SAE classified as related (myalgia) occurred in a subject who received a control 
product. Four SAEs classified as related occurred in recipients of an adjuvanted H5N1 vaccine: 
autoimmune hepatitis, angina pectoris, pulmonary embolism, and non-Hodgkin’s lymphoma. One 
SAE classified as related (lobar pneumonia) occurred in a recipient of an unadjuvanted H5N1 
vaccine. Overall, the reactogenicity and safety profile of AS03-adjuvanted pandemic vaccines is 
acceptable and no safety concerns have been identified in clinical trials. 
Narcolepsy is a chronic sleep disorder with a background incidence rate, based on US data, of 
approximately 1.37 per 100,000 per year, with a peak onset between 10 and 19 years of age in 
some datasets. Narcolepsy, when associated with cataplexy is seen almost exclusively in 
individuals who are HLA DQB1*0602 allele carriers[68]. An autoimmune etiology has been 
proposed. In the post-marketing period for adjuvanted H1N1 pandemic vaccines, several 
epidemiological studies conducted in several countries independently of GSK reported an 
increased risk of narcolepsy with or without cataplexy in subjects who were vaccinated with 
Dresden-manufactured H1N1 (Pandemrix™ H1N1) vaccine during the 2009-2010 season. These 
studies have described an absolute risk increase of narcolepsy of approximately 1.4 to 8 additional 
cases per 100,000 vaccinated children/adolescents, and approximately one additional case per 
100,000 vaccinated adults compared to background rates of 0.12 to 0.79 per 100,000 
children/adolescents per year and 0.67 to 1.10 per 100,000 adults per year. The observed temporal 
association between narcolepsy and vaccination with Pandemrix™ H1N1 is not fully understood, 
and further research to evaluate the association between narcolepsy and Pandemrix™ H1N1, and 
other possible contributory factors to the development of narcolepsy during the 2009-2010 
pandemic, such as genetic and environmental factors, is being conducted. A GSK-supported 
study was conducted in Quebec, Canada, to assess the risk of narcolepsy associated with 
Arepanrix H1N1, using various index dates, risk periods, observation periods, and 
epidemiological designs. Overall, GSK considers that there is no strong evidence of an 
association between Q-Pan-H1N1 and narcolepsy in Quebec.  Recently, the CDC conducted a 
study to assess trends in narcolepsy incidence rates before and after 2009 H1N1 influenza 
(pH1N1) vaccination campaigns and to evaluate the risk of narcolepsy following adjuvanted 
pH1N1 vaccines. Results of the incidence rates analysis indicated no change in narcolepsy rates 
between the period before wild-type pH1N1 virus circulation and the period after the start of 
pH1N1vaccination campaigns in any countries except Sweden, the first signaling country, and 
Taiwan, where incidence began to increase upon wild-type pH1N1 virus circulation. In the case-
control analysis, no association was observed for AS03-adjuvanted pH1N1 vaccine and 
narcolepsy in children or adults, and in the case-coverage analysis no association was observed 
for narcolepsy in children, the only age groups studied. However, the data for the AS03-
adjuvanted pH1N1 vaccine, Pandemrix™, were limited. (20th Annual Conference on Vaccine 
Research, April 24-26th, 2017, Abstract S6-1). 


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No post-marketing data are available for AS03 administered in combination with any GSK-
manufactured H5N1, H7N1, H7N9, or H9N2 antigen. However, millions of doses of GSK-
manufactured H1N1 antigens, combined with AS03, were administered in the context of the 
2009/10 pandemic response. In addition to the adverse reactions reported in clinical trials, the 
following have been reported during post-marketing experience with Pandemrix™ (H1N1) and 
Arepanrix™ (H1N1): 
• Immune system disorders 
o Rare: anaphylaxis, allergic reactions 
• Nervous system disorders 
o Rare: febrile convulsions (in subjects below 20 years of age), somnolence**, 
Guillain-Barré syndrome* 
*Spontaneous reports of Guillain-Barré syndrome have been received following 
vaccination with Arepanrix™ (H1N1); however, a causal association between 
vaccination and Guillain-Barré syndrome has not been established. Data from a post-
marketing epidemiological study in Canada indicate a small but significant increased 
relative risk of Guillain-Barré syndrome of 1.80 (95% CI, 1.63-4.62) in the 56-day 
period following vaccination with Arepanrix™ (H1N1, in persons 50 years of age 
and older). The number of GBS cases attributable to vaccination was approximately 
2 per 1 million doses. 
**reported in patients with narcolepsy and as a temporary event following 
vaccination 
o Very rare1: narcolepsy with or without cataplexy 
1Frequency based on estimated attributable risk from epidemiological studies in 
several European countries. 
• Skin and subcutaneous tissue disorders 
o Rare: angioedema, generalized skin reactions, urticaria 
• General disorders and administration site conditions 
o Rare: injection site reactions (such as inflammation, mass, ecchymosis) 


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From post-marketing surveillance with interpandemic (seasonal) trivalent vaccines, the following 
additional AEs have been reported: 
• Blood and lymphatic system disorders 
o Transient thrombocytopenia 
• Nervous system disorders 
o Neuralgia, convulsions 
o Neurological disorders, such as encephalomyelitis, neuritis, and Guillain-Barré 
syndrome 
• Vascular disorders 
o Vasculitis with transient renal involvement 
As of November 22, 2015, the available data for women who become pregnant during clinical 
trials of AS03-adjuvanted (pre) pandemic influenza vaccines do not suggest any causal 
relationship between adverse pregnancy outcomes and receipt of an AS03-adjuvanted vaccine. 
However, there is no available data related to the risks of exposure to H7N9 vaccines 
administered with or without AS03 upon pregnancy and pregnancy outcomes. 
Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that 
unauthorized persons will see the subject’s PHI. All study records will be kept in a locked file 
cabinet or maintained in a locked room at the participating VTEU sites. Electronic files will be 
password-protected. Only people who are involved in the conduct, oversight, monitoring, or 
auditing of this trial will be allowed access to the PHI that is collected. Any publications from 
this trial will not use information that will identify subjects by name. Organizations that may 
inspect and/or copy research records maintained at the participating VTEU sites for quality 
assurance and data analysis include groups such as the local Institutional Review Board (IRB), 
NIAID, and the FDA. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
US Law. This web site will not include information that can identify subjects.  
There may be other risks, discomforts, or side effects that are unknown at this time. 


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2.3.2 
Known Potential Benefits 
There are no known benefits attributable to the receipt of the 2017 H7N9 IIV with or without 
AS03 adjuvant. Vaccination using the 2017 H7N9 IIV with or without AS03 adjuvant may or 
may not provide protection against a serious disease with the influenza 2017 H7N9 virus, should 
the participant be exposed. The duration of any such protection is currently unknown. The 2017 
H7N9 IIV with or without AS03 adjuvant is not expected to offer protection against circulating 
seasonal influenza viruses. There may be pandemic preparedness benefits to society in the future 
if the vaccine and adjuvants being evaluated in this clinical trial prove to be sufficiently safe and 
immunogenic and can be employed if a need for widespread influenza 2017 H7N9 vaccination 
occurs. 


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3 
STUDY OBJECTIVES AND OUTCOME MEASURES 
3.1 
Study Objectives 
3.1.1 
Primary 
Safety: 
• To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV 
administered intramuscularly at different dosages approximately 21 days apart given with 
or without AS03 adjuvant  
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody 
responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly 
at different dosages approximately 21 days apart with or without AS03 adjuvant, 
stratified by age of recipient. 
3.1.2 
Secondary  
Safety: 
• To assess unsolicited non-serious adverse events (AEs) following receipt of two doses of 
a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with 
or without AS03 adjuvant  
• To assess medically-attended adverse events (MAAEs) including new-onset chronic 
medical conditions (NOCMCs), potentially immune-mediated medical conditions 
(PIMMCs), and all serious adverse events (SAEs) following receipt of two doses of a 
2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with 
or without AS03 adjuvant  
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses approximately 7 and 21 days 
following receipt of a single dose, and approximately 7 days following receipt of two 
doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days 
apart with or without AS03 adjuvant, stratified by age of recipient. 


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3.1.3 
Exploratory 
Immunogenicity: 
• To assess the effects of age, sex, body mass index, and prior receipt of seasonal influenza 
vaccine(s) on serum HAI and Neut antibody responses following receipt of two doses of 
a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with 
or without AS03 adjuvant. 
• To assess, in at least a subset of samples, the cross-reactivity of serum HAI and Neut 
antibody responses to antigenically drifted variants of influenza A/H7 viruses following 
receipt of two doses of a 2017 H7N9 IIV administered intramuscularly at different 
dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of 
recipient.  
• To assess the durability of serum HAI and Neut antibody responses at approximately 180 
days following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at 
different dosages approximately 21 days apart with or without AS03 adjuvant, stratified 
by age of recipient.  
• 
To assess the NA content of the 2017 H7N9 IIV and determine the serum antibody responses to 
NA following receipt of 2017 H7N9 IIV. 
3.2 
Study Outcome Measures 
3.2.1 
Primary 
Safety: 
• 
Occurrence of study vaccine-related serious adverse events (SAEs) from the time of the 
first study vaccination through approximately 12 months after the last study vaccination. 
• 
Occurrence of solicited injection site and systemic reactogenicity events from the time of 
each study vaccination through 7 days after each study vaccination. 
• 
Occurrence of clinical safety laboratory adverse events from the time of each study 
vaccination through approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
the influenza 2017 H7N9 study vaccine strain (defined as either a pre-vaccination titer 
<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a minimum 


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four-fold rise in post-vaccination titer) at approximately 21 days after the second study 
vaccination (Study Day 43). 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥1:40 against the 
influenza 2017 H7N9 study vaccine strain at approximately 21 days after the second 
study vaccination (Study Day 43). 
• Geometric Mean Titers (GMTs) of serum HAI and Neut antibodies against the influenza 
2017 H7N9 vaccine strain at approximately 21 days after the second study vaccination 
(Study Day 43).  
3.2.2 
Secondary 
Safety: 
• 
Occurrence of study vaccine-related unsolicited non-serious AEs from the time of each 
study vaccination through approximately 21 days after each study vaccination. 
• 
Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness 
or relatedness, from the time of each study vaccination through approximately 21 days 
after each study vaccination.  
• 
Occurrence of MAAEs, including NOCMCs, and PIMMCs from the time of the first 
study vaccination through approximately 12 months after the last study vaccination. 
• 
Occurrence of all serious adverse events (SAEs), regardless of the assessment of 
relatedness, from the time of the first vaccination through approximately 12 months after 
the last study vaccination.  
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
the influenza 2017 H7N9 vaccine strain at approximately 7, 21, and 28 days after the first 
study vaccination (Study Days 8, 22, 29). 
• 
For HAI and Neut antibodies, percentage of subjects achieving titers of 1:40 or greater 
against the influenza 2017 H7N9 vaccine strain at baseline and approximately 7, 21, and 
28 days after the first study vaccination (Study Days 8, 22, 29). 
• 
GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine virus 
at baseline and approximately 7, 21, and 28 days after the first study vaccination (Study 
Days 8, 22, 29).  


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3.2.3 
Exploratory 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects achieving seroconversion and the 
Geometric Mean Titers of serum HAI antibody against the 2017 H7N9 study vaccine 
strain approximately 21 and 180 days after the second study vaccination (Study Days 43 
and 202), stratified by age, sex, body mass index, and prior receipt of seasonal influenza 
vaccine(s). 
• 
For HAI and Neut antibodies, for at least a subset of subjects, percentage achieving 
seroconversion, percentage with titer ≥1:40, and Geometric Mean Titers against 
antigenically drifted variants of influenza A/H7 viruses at baseline and approximately 21 
and 180 days after the second study vaccination (Study Day 43 and 202). 
• 
For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40, and Geometric Mean Titers against the 2017 H7N9 study 
vaccine strain at approximately 180 days after the second study vaccination (Study Day 
202). 
• 
Percentage of subjects with detectable levels of serum N9 NA specific antibody elicited 
by 2017 H7N9 vaccination, and the correlation of the NA content of 2017 H7N9 IIV with 
the elicited NA specific antibody responses at baseline and approximately 8 and 21 days 
after the first study vaccination (Study Day 1, 9 and 21) and 8, 21 and 180 days after the 
second study vaccination (Study Day, 29, 43 and 202). 
 


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4 
STUDY DESIGN 
This is a randomized, double-blinded, Phase II study in males and non-pregnant females, who 
are in good health, aged 19 years and older. This clinical trial is designed to assess the safety, 
reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza 
A/H7N9 virus vaccine (2017 H7N9 IIV),), manufactured by Sanofi Pasteur, administered at 
different dosages given 1) with AS03 adjuvant and Phosphate Buffered Saline (PBS) diluent 
[manufactured by GlaxoSmithKline (GSK) and Sanofi Pasteur, respectively], (3.75 mcg of HA 
per dose), 2) with AS03 adjuvant (7.5 mcg and 15 mcg HA per dose),), or 3) without adjuvant 
(15 mcg and 45 mcg of HA per dose). The 2017 H7N9 IIV was manufactured using a reverse 
genetics-derived reassortant candidate vaccine virus IDCDC RG56B (H7N9), containing the HA 
and NA from low pathogenic influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, 
NP, M and NS from A/Puerto Rico/8/1934 (H1N1). 
Subjects who are in good health and meet all eligibility criteria (including an erythrocyte 
sedimentation rate [ESR], urine or serum pregnancy test, history and physical exam) within 28 
days prior to the first vaccination or on the day of, but prior to, first vaccination, will be 
randomized into one of 5 study groups, stratified by age as shown in Table 1. Baseline clinical 
safety laboratories will be drawn prior to the first vaccine dose and will not be used to screen 
subjects for eligibility. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study vaccination. 
Unsolicited non-serious AEs will be collected from the time of each study vaccination through 
approximately 21 days after each study vaccination. SAEs, MAAEs, including NOCMCs, and 
PIMMCs, will be collected from the time of the first study vaccination through approximately 12 
months after the last study vaccination. Clinical laboratory evaluations for safety will be 
performed on venous blood collected prior to each study vaccination and approximately 7 days 
after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 2017 
H7N9 vaccine virus on serum samples obtained immediately prior to each study vaccination 
(Days 1 and approximately Day 22), approximately 7 days after each study vaccination (Days 8 
and 29), and approximately 21 and 180 days after the second study vaccination (Days 43 and 
202). 
Novel methods for identifying and assessing alternative correlates of protection against influenza 
infection are needed.  To assess the NA specific antibody response to vaccination, it is first 
necessary to determine the NA content of inactivated influenza vaccine; this assay is under 


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development.  If successful, the NA content in a dosage specific manner can be correlated to the 
N9 NA-specific antibody responses elicited by the 2017 H7N9 IIV. 
Subjects who have not received licensed 2017-2018 seasonal trivalent or quadrivalent inactivated 
influenza vaccine (IIV3 or IIV4, including high dose vaccine for the elderly) prior to being 
enrolled in the study may receive it anytime following completion of the Day 43 study visit or 
upon early termination.  
For additional details on study procedures and evaluations and study schedule by study 
visits/days, see Sections 7 and 8 and Appendix A: Schedule of Study Procedures and 
Evaluations. 


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5 
STUDY ENROLLMENT AND WITHDRAWAL 
Approximately 400 (up to 420) individuals 19-64 years old, and approximately 240 (up to 300) 
greater than or equal to (≥) 65 years old, males and non-pregnant females, who are in good 
health by history and meet all eligibility criteria, will be enrolled at up to 9 VTEU sites 
participating in this trial. The target population should reflect the community at large at each of 
the participating VTEU sites. Estimated time to complete enrollment in this trial is 
approximately 12 weeks. Information regarding this trial may be provided to potential subjects 
who have previously participated in vaccine trials conducted at the participating VTEU sites. 
Other forms and/or mechanisms of recruitment may also be used. The local Institutional Review 
Board (IRB) will approve all materials prior to use. 
Subject Inclusion and Exclusion Criteria must be assessed by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or sub-
investigator. 
No exemptions are granted on Subject Inclusion or Exclusion Criteria in DMID-sponsored 
studies. Questions about eligibility should be directed toward the DMID Medical Officer. 
5.1 
Eligibility Criteria 
5.1.1 
Subject Inclusion Criteria 
Subjects eligible to participate in this trial must meet all of the following inclusion criteria: 
1. Provide written informed consent prior to initiation of any study procedures. 
2. Are able to understand and comply with planned study procedures and be available for all 
study visits. 
3. Are males or non-pregnant females, 19 years of age and older, inclusive. 
4. Are in good health1. 
1As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical 
diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment 
of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should 
be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition and no adverse symptoms that need 
medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription 
medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days 
prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or 
that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this 
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the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion 
criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator 
or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and 
immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes 
subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject’s 
chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or 
interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with 
the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria (see Section 5.1.2), herbals, 
vitamins, and supplements are permitted. 
5. Oral temperature is less than 100.0°F. 
6. Pulse is 47 to 100 bpm, inclusive. 
7. Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects <65 years of age), 85 to 
160 mmHg, inclusive (subjects > 65 years of age). 
8. Diastolic blood pressure is 55 to 95 mmHg, inclusive. 
9. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour. 
10. Women of childbearing potential2 must use an acceptable contraception method3 from 30 
days before first study vaccination until 60 days after last study vaccination. 
2Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® 
placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at 
least 90 days after the procedure, and still menstruating or <1 year of the last menses if menopausal. 
3Includes, , non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous 
relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving 
the first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective 
intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, injectables, or oral contraceptives 
(“the pill”). 
11. Women of childbearing potential must have a negative urine or serum pregnancy test 
within 24 hours prior to study vaccination. 
5.1.2 
Subject Exclusion Criteria 
Subjects eligible to participate in this trial must not meet any of the following exclusion criteria: 
1. Have an acute illness4, as determined by the site principal investigator or appropriate sub-
investigator, within 72 hours prior to study vaccination. 
4An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion 
of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the 
ability to assess safety parameters as required by the protocol. 


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2. Have any medical disease or condition that, in the opinion of the site principal 
investigator or appropriate sub-investigator, is a contraindication to study participation5. 
5Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place 
the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may 
interfere with the evaluation of responses or the subject’s successful completion of this trial. 
3. Have immunosuppression as a result of an underlying illness or treatment, a recent 
history or current use of immunosuppressive or immunomodulating disease therapy.  
4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to 
study vaccination. 
5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-
melanoma, treated, skin cancers are permitted. 
6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 
7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based 
adjuvants, or other components of the study vaccine. 
8. Have a history of severe reactions following previous immunization with licensed or 
unlicensed influenza vaccines. 
9. Have a personal or family history of narcolepsy. 
10. Have a history of Guillain-Barré syndrome. 
11. Have a history of convulsions or encephalomyelitis within 90 days prior to study 
vaccination. 
12. Have a history of PIMMCs6 
6Refer to Appendix B: List of Potentially Immune-Mediated Medical Conditions. 
13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination. 
14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric 
diagnosis that may interfere with subject compliance or safety evaluations. 
15. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement 
for danger to self or others within 10 years prior to study vaccination. 


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16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 
30 days prior to study vaccination. 
17. Have taken high-dose inhaled corticosteroids7 within 30 days prior to each study 
vaccination. 
7High-dose defined as per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-
pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses  
18. Received a licensed live vaccine within 30 days prior to the first study vaccination, or 
plan to receive a licensed live vaccine within 30 days before or after each study 
vaccination. 
19. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu vaccines) 
within 14 days before or after each study vaccination.  
20. Received or plan to receive an inactivated seasonal flu vaccine within 21 days before or 
after each study vaccination.  
21. Received immunoglobulin or other blood products (with exception of Rho D 
immunoglobulin) within 90 days prior to each study vaccination. 
22. Received an experimental agent8 within 30 days prior to the first study vaccination, or 
expect to receive an experimental agent9 during the 13-month trial-reporting period. 
8Including vaccine, drug, biologic, device, blood product, or medication. 
9Other than from participation in this trial. 
23. Are participating or plan to participate in another clinical trial with an interventional 
agent10 that will be received during the 13-month trial-reporting period. 
10Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. 
24. Received or plan to receive an influenza A/H7 vaccine11 or have a history of influenza 
A/H7 subtype infection.  
11And assigned to a group receiving influenza A/H7 vaccine, does not apply to documented placebo recipients. 
25. Have traveled to mainland China and had substantial12 direct contact with live or freshly 
slaughtered poultry or pigeons within the past five years. 
12substantial contact is defined as visited a poultry farm and/or a live poultry market.  
26. Occupational exposure to or substantial direct physical contact13 with birds in the past 
year and through the 21 days after the second study vaccination. 


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13Exposure to free range chickens in the yard is exclusionary. Casual contact with birds at petting zoos or county or 
state fairs or having pet birds does not exclude subjects from study participation. 
27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the 
first study vaccination until 30 days after the last study vaccination. 
28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment 
through 21 days after the second study vaccination. 
5.2 
Treatment Assignment Procedures 
5.2.1 
Enrollment and Randomization Procedures 
Per ICH guideline E6: Good Clinical Practice (GCP), screening records will be kept at each 
participating VTEU site to document the reason why an individual was screened, but failed trial 
entry criteria. The reasons why individuals failed screening will be recorded in the Statistical and 
Data Coordinating Center’s (SDCC) AdvantageEDCSM (Electronic Data Capture System). 
Once consented and upon entry of demographic data and confirmation of eligibility for this trial, 
the subject will be enrolled, randomly assigned to 1 of 5 treatment groups. All subjects will 
receive 2 vaccinations; the same dose will be given to the subject at both the first and second 
vaccination. Subjects will be randomized with allocation 2:2:2:1:1 into 5 groups, stratified by 
site and age (see Table 1) to receive IM 2017 H7N9 IIV at 3.75 mcg, 7.5 mcg or 15 mcg at Days 
1 and 22 with AS03 adjuvant or 15 mcg or 45 mcg at Days 1 and 22 administered without 
adjuvant. 
Enrollment of subjects will be done online using the enrollment module of AdvantageEDCSM. 
The randomization code will be prepared by statisticians at the SDCC and included in the 
enrollment module for this trial. AdvantageEDCSM will assign each subject to a treatment arm 
after the demographic and eligibility data have been entered into the system. A designated 
individual at each participating VTEU site will be provided with a code list for emergency 
unblinding purposes, which will be kept in a secure place. 
Instructions for use of the enrollment module are included in the AdvantageEDCSM User’s 
Guide. Manual back-up procedures and instructions are provided for use in the event that a 
participating VTEU site temporarily loses access to the Internet or the online enrollment system 
is unavailable. 
Over-enrollment is allowed to account for subjects who do not receive the full schedule of study 
vaccinations, as shown in Table 1. 


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5.2.2 
Masking Procedures 
This is a double-blind clinical trial. 
Subjects, investigators, study personnel performing any study-related assessments following 
study vaccine administration are blinded to study treatment. Laboratory personnel performing 
HAI and Neut antibody assays will receive serum samples blinded to subject ID number and 
sample visit number. 
The randomization scheme will be generated by the SDCC and provided to unblinded study 
personnel (i.e., research pharmacists performing study vaccination preparations and unblinded 
study vaccine administrators) at the participating VTEU sites. 
The unblinded study vaccine administrator is a study personnel member credentialed to 
administer vaccines and may also participate in dose preparation, but will not be involved in 
study-related assessments or have subject contact for data collection following study vaccine 
administration. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented by 
treatment arm. The DSMB may also be provided with expected and observed rates of the 
expected AEs in an unblinded fashion, and may request the treatment arm be unblinded for an 
individual subject if required for safety assessment. The DSMB will review grouped and 
unblinded data in the closed session only. 
5.2.3 
Reasons for Withdrawals and Discontinuation of Treatment 
Subjects may voluntarily withdraw their consent for trial participation at any time and for any 
reason, without penalty. 
A subject may withdraw or be withdrawn from this trial for any of the following reasons: 
• Medical disease or condition, or any new clinical finding for which continued 
participation, in the opinion of the site principal investigator or appropriate sub-
investigator, would compromise the safety of the subject, or would interfere with the 
subject's successful completion of this trial, or would interfere with the evaluation of 
responses (for example, has baseline significant laboratory abnormalities). 
• Subject no longer meets eligibility criteria (see Section 5.1). Note: Medication changes in 
the 60 days prior to enrollment, as specified in Subject Inclusion Criterion #4, are 
exclusionary for receipt of the first study vaccination only. 


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• As deemed necessary by the site principal investigator or appropriate sub-investigator for 
noncompliance or other reasons. 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• New information becomes available that makes further participation unsafe. 
The second study vaccination will not be administered to a subject if any of the following criteria 
are met: 
• Medical condition or medication change for which continued participation, in the opinion 
of the site principal investigator or appropriate sub-investigator, would pose a risk to the 
subject or would be likely to confound interpretation of the results. 
• Presence of signs or symptoms that could confound or confuse assessment of study 
vaccine reactogenicity. For subjects with injection site or systemic signs or symptoms, or 
with an acute illness, including an oral temperature greater than or equal to 100°F, the 
second study vaccination should be postponed/deferred until signs, symptoms, or acute 
illness have resolved, or are improving as further specified below, and if within the 
acceptable protocol-specified window for that visit (Day 22+7).). No exceptions to the 
protocol-specified window will be made. Note for afebrile, acute illness only: If a 
subject is afebrile, his/her acute illness is nearly resolved with only minor residual 
symptoms remaining, this occurs within the acceptable protocol-specified window for 
that visit (Day 22+7), and, in the opinion of the site principal investigator or appropriate 
sub-investigator, the residual symptoms will not interfere with the ability to assess safety 
parameters as required by the protocol, the subject may receive the second study 
vaccination without further approval from the DMID Medical Officer. No exceptions to 
the protocol-specified window will be made. Grade 3 solicited or unsolicited AE that is 
ongoing, whether or not it is improved or resolving.  
• Any unresolved or continuing Grade 2 AE that has not decreased in severity to Grade 1 
or less.   
• An unresolved or continuing Grade 1 AE is permissible following the documented 
determination by the site PI or appropriate sub-investigator, that it would not render study 
vaccination unsafe or interfere with the evaluation of responses. 


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• Grade 3 solicited or unsolicited AE that occurs without alternative etiology in the 8 days 
following the first study vaccination. 
• Grade 3 clinical safety laboratory value (according to the toxicity table, Section 9.2.3) 
that does not decrease to Grade 2 or less prior to the second study vaccination. Any 
clinical safety laboratory parameter may be re-evaluated only once at the central (clinical) 
laboratory in order to assess eligibility prior to the second study vaccination. If the 
clinical safety laboratory value decreases to Grade 2 or less, the subject may receive the 
second study vaccination. The second study vaccination should be scheduled to occur 
within the acceptable protocol-specified window for that visit (Day 22+7 days post first 
study vaccination). No exceptions to the protocol-specified window will be made. 
• New onset of illness or condition that meets the Subject Exclusion Criteria (see Section 
5.1.2). 
• Hospitalization that occurs before administration of the second study vaccination.  
• Subject no longer meets eligibility criteria (see Section 5.1). Note: Medication changes 
subsequent to the first study vaccination are not exclusionary for receipt of the second 
study vaccination provided there was no deterioration in the subject’s chronic medical 
condition that necessitated a medication change, and there is no additional risk to the 
subject or interference with the evaluation of responses to study vaccination. 
• As deemed necessary by the site principal investigator or appropriate sub-investigator for 
noncompliance or other reasons. 
• Subject refusal of further study vaccination. 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• New information becomes available that makes further participation unsafe. 
5.2.4 
Handling of Withdrawals and Discontinuation of Treatment 
The primary reason for withdrawal from this trial will be recorded on the Study Status data 
collection form. Subjects will be encouraged to complete the Early Termination Visit. The Early 
Termination Visit procedures are listed in Section 8.2.11. 


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Although subjects are free to withdraw at any time or may be withdrawn by the site principal 
investigator or appropriate sub-investigator at any time (see Section 5.2.3), those subjects who 
receive only one dose of study vaccine will be encouraged to remain in this trial for follow-up 
safety assessments (may be conducted by phone call rather than in person) continuing through 
approximately 12 months after their last study vaccination. These subjects will also be 
encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 
days and 180 days after their last study vaccination, if applicable. See the protocol-specific 
Manual of Procedures (MOP) for alternate follow-up requirements. 
Every attempt will be made to follow all AEs, including solicited injection site and systemic 
reactions, unsolicited non-serious AEs, SAEs, MAAEs, including NOCMCs, and PIMMCs, 
ongoing at the time of early withdrawal through resolution as per applicable collection times 
defined for the specific type of AE. 
In the case of subjects who fail to appear for a follow-up safety assessment, extensive effort (i.e., 
three documented contact attempts via phone calls made on separate occasions and followed by a 
certified letter) will be made to locate or recall them, or at least to determine their health status. 
These efforts will be documented in the subject’s study records. 
Subjects who withdraw, or are withdrawn or terminated from this trial, or are lost to follow-up 
after signing the informed consent form, randomization, and receipt of study vaccine will not be 
replaced.  
5.2.5 
Termination of Study 
Although the sponsor has every intention of completing this trial, it reserves the right to 
terminate this trial at any time for clinical or administrative reasons. Reasons for termination 
include, but are not limited to, study closure due to DSMB review and recommendation and at 
the discretion of DMID. 


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6 
STUDY INTERVENTION/INVESTIGATIONAL 
PRODUCT 
6.1 
Study Product Description 
2017 H7N9 IIV 
Sanofi Pasteur has developed a monovalent 2017 H7N9 IIV manufactured from a reverse 
genetics-derived reassortant virus containing the HA and NA from influenza A/Hong 
Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 
(H1N1). The manufacturing process for the production of this monovalent 2017 H7N9 IIV is 
similar to the manufacturing process used to produce the licensed IIV Fluzone® family of 
products. 
 
 
 
 
 
 
PBS Diluent 
The PBS diluent was produced in accordance with the commercial process utilized in 
manufacture of 
 PBS buffer/diluent for the formulation of Fluzone®, influenza virus 
vaccine. 
AS03 Adjuvant [Adjuvant System AS(03)] 
 
6.1.1 
Acquisition 
2017 H7N9 IIV will be provided by Sanofi Pasteur under contract to BARDA/DHHS. 
The PBS diluent will be provided by Sanofi Pasteur under contract to BARDA/DHHS. 
AS03 adjuvant will be provided by GSK under contract to BARDA/DHHS. 


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Upon request by DMID, 2017 H7N9 IIV, PBS diluent, and AS03 adjuvant will be transferred to 
the following address: 
DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
 
 
  
 
Sterile empty vials will be obtained by the DMID Clinical Materials Services (CMS), Fisher 
BioServices. 
2017 H7N9 IIV, PBS diluent, AS03 adjuvant, and sterile empty vials for study vaccine 
preparation will be provided through the DMID CMS to the participating VTEU sites prior to the 
start of this trial upon request and with prior approval from DMID. Should the site principal 
investigator require additional 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, or sterile empty 
vials during this trial, further instructions are provided in the protocol-specific MOP. 
6.1.2 
Formulation, Storage, Packaging, and Labeling 
2017 H7N9 IIV 
Investigational influenza virus A/Hong Kong vaccine (H7N9), a monovalent type A inactivated 
vaccine for IM use, is a sterile suspension prepared from pandemic influenza virus candidate 
vaccine propagated in embryonated chicken eggs. The vaccine contains no preservative 
(thimerosal). No components of this vaccine contain latex. It is essentially clear and slightly 
opalescent in color and supplied in single-dose glass vials. The vials must be stored at 2°C to 
8°C (36°F to 46°F). Do not freeze. Vials will be provided with latex-free stoppers. 
 
 
 
 
 
 
 


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Specific mixing instructions are included in the MOP to achieve specific dosages. 
PBS Diluent 
 
 
It is 
essentially clear and slightly opalescent in color and must be stored at 2°C to 8°C (36°F to 46°F). 
Vials will be provided with latex-free stoppers. 
AS03 Adjuvant [Adjuvant System (03)] 
The AS03 adjuvant is supplied as a preservative-free, oil-in-water, whitish to yellowish 
homogenous milky liquid emulsion presented in a 3 mL Type I, single-use glass vials. The vials 
must be stored at 2°C to 8°C (36°F to 46°F). Do not freeze. Vials will be provided with latex-
free stoppers. 
Each of these study products will be labeled according to manufacturer specifications and 
include the statement “Caution: New Drug Limited by Federal Law to Investigational Use.” 
Further details are included in the respective, applicable Investigator’s Brochures for the 2017 
H7N9 IIV, AS03 adjuvant, as well as in the protocol-specific MOP. 
Sterile empty vials will be provided with latex-free stoppers. 
6.1.3 
Study Product Storage and Stability Procedures 
The temperature of the storage unit must be manually recorded daily (excluding non-business 
days and holidays as applicable) and continuously monitored and recorded during the duration of 
this trial per the participating VTEU site standard operating procedures (SOPs), and 
documentation will be maintained. If the temperature fluctuates outside of the required range, the 
affected study product(s) must be quarantined at the correct storage temperature and labeled as 
‘Do Not Use’ (until further notice). The research pharmacist must alert the site principal 
investigator and study coordinator, if the temperature fluctuates outside of the required range. In 
the event the temperature fluctuates outside of the required range, including accidental deep-
freezing or disruption of the cold chain, the affected study product(s) must not be administered. 
The site principal investigator or responsible person should immediately contact the DMID 
Product Support Team at DMIDProductSupportTeam@niaid.nih.gov for further instructions 
before any additional study vaccinations are administered. Based on the information collected, 
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If it cannot be used, the site will receive specific instructions on how to return the affected study 
product(s) to the DMID CMS or destroy it on site.   
6.2 
Dosage, Preparation, and Administration of Study Intervention/ 
Investigational Product 
See the protocol-specific MOP Appendices for detailed information on the preparation, labeling, 
storage, and administration of study vaccine for each treatment arm. Study vaccine preparation 
will be performed by the participating VTEU site research pharmacist on the same day of study 
vaccine administration. 
Visually inspect the 2017 H7N9 IIV, PBS diluent and AS03 adjuvant upon receipt and prior to 
use. If the study product(s) appear(s) to have been damaged, contaminated or discolored, contain 
visible particulate matter   or if there are any concerns regarding its integrity, do NOT use the 
affected study product(s). The affected study product(s) must be quarantined at 2°C to 8°C (36°F 
to 46°F) and labeled as ‘Do Not Use’ (until further notice). The site principal investigator or 
responsible person should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project Manager for further 
instructions before any additional study vaccinations are administered. Based on the information 
collected, DMID and/or the manufacturer will determine whether the affected study product(s) 
can be used. If it cannot be used, the site will receive specific instructions on how to return the 
affected study product(s) to the DMID CMS or destroy it on site. If the 2017 H7N9 IIV , PBS 
diluent or the AS03 adjuvant is unusable, study personnel will use another vial from the study 
supply. Replacement vials may be requested by contacting DMID. Additional instructions for 
quarantine and DMID contact information are provided in the protocol-specific MOP. 
For those doses that must be admixed with AS03, visually inspect the 2017 H7N9 IIV/PBS 
diluent plus adjuvant admixture prior to use. The admixture will be milky in appearance. If it 
appears to have been damaged, contaminated or discolored, contain visible particulate matter, or 
if there are any concerns regarding its integrity, do NOT use it. The affected 2017 H7N9 
IIV/PBS diluent plus adjuvant admixture must be quarantined at room temperature and labeled 
as ‘Do Not Use’ (until further notice). The site principal investigator or responsible person 
should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project Manager for further 
instructions before any additional study vaccinations are administered. Based on the information 
collected, DMID and/or the manufacturer will determine whether the 2017 H7N9 IIV/PBS 
diluent plus adjuvant admixture can be used. If it cannot be used, the site will receive specific 
instructions on how to send the 2017 H7N9 IIV/PBS diluent plus adjuvant admixture to the 
DMID CMS or destroy it on site. If the 2017 H7N9 IIV/PBS diluent plus adjuvant admixture is 


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unusable, the participating VTEU sites’ research pharmacist will prepare another vial. Additional 
instructions for quarantine and DMID contact information are provided in the protocol-specific 
MOP. 
For those doses that must be admixed with AS03, the 2017 H7N9 IIV/PBS diluent plus adjuvant 
admixture, once mixed, must be stored at room temperature in an upright position and must be 
used within 8 hours.  Gently invert the final mixed vial 5 to 7 times immediately before the 
single dose is withdrawn.  Do not shake the final mixed vial.  Only one dose should be 
withdrawn from the final mixed vial. 
Once mixed, the A/H7N9 unadjuvanted vaccine admixture for the 45 mcg/dose study group 
(Group 5) must be stored at 2°C to 8°C (36°F to 46°F) and must be used within 8 hours. 
Study vaccine administration will be performed by an unblinded study personnel member who is 
credentialed to administer vaccines and may also participate in dose preparation, but will not be 
involved in study-related assessments or have subject contact for data collection following study 
vaccine administration. Each dose of study vaccine will be administered via a single IM injection 
given in the deltoid muscle of the subjects’ preferred arm. The site of injection (right or left arm) 
will be recorded on the appropriate data collection form. Aseptic technique will be used for the 
withdrawal and administration of each dose of study vaccine using a disposable sterile needle 
appropriate in length for each subject and a disposable sterile 1-mL syringe. See the protocol-
specific MOP for information on how to administer IM injections. Each dose of study vaccine 
must be administered within 30 minutes of drawing into the syringe (not to exceed 8 hours total 
since admixing time), and the prepared syringe must be stored at room temperature until 
administered.  
Dose calculations are based on the actual HA content per 0.5 mL. Each 0.5 mL dose of AS03 
adjuvanted study vaccine contains one 0.25 mL dose of AS03 adjuvant. 
6.3 
Modification of Study Intervention/Investigational Product for a 
Subject 
There will be no dose modifications. If a subject’s second study vaccination is deferred, it should 
be rescheduled to occur within the acceptable protocol-specified window for that visit (Day 22+7 
days post first study vaccination). No exceptions to the protocol-specified window will be made. 


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6.4 
Accountability Procedures for the Study Intervention/ 
Investigational Product 
After receipt of the 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, and sterile empty vials, the site 
principal investigator is responsible for study product distribution and disposition, and has 
ultimate responsibility for study product accountability. The site principal investigator may 
delegate to the participating VTEU sites’ research pharmacist responsibility for study product 
accountability. The participating VTEU sites’ research pharmacist will be responsible for 
maintaining complete records and documentation of study product receipt, accountability, 
dispensation, storage conditions, and final disposition of the study product(s). The study product 
accountability records and dispensing logs will also capture vial numbers, including final mixed 
vial number, date of study vaccine preparation/administration, time of study vaccine preparation, 
expiration of study vaccine preparation, time study vaccine is drawn into the syringe, and amount 
of study vaccine withdrawn for administration. Time of study vaccine administration to the 
subject will be captured on the appropriate data collection form. All study product(s), including 
the amount of 2017 H7N9 IIV, AS03 adjuvant, and admixture, whether administered or not, 
must be documented on the appropriate study product accountability record or dispensing log. 
The sponsor's monitoring staff will verify the participating VTEU sites’ study product 
accountability records and dispensing logs per the site monitoring plan. 
Used and unused vials of 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, and admixture will be 
retained until monitored and released for disposition as applicable. This can occur on an ongoing 
basis for used vials of 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, and admixture. Used vials 
of A/H7N9 vaccine, PBS diluent, AS03 adjuvant and admixture may be destroyed in accordance 
with site-specific SOPs following each monitoring visit where Study Product Accountability is 
monitored, and resolution of any discrepancies. Final disposition of the unused 2017 H7N9 IIV, 
PBS diluent, AS03 adjuvant, and sterile empty vials will be determined by DMID and 
communicated to the participating VTEU sites by the DMID Clinical Project Manager. 
6.5 
Assessment of Subject Compliance with Study Intervention/ 
Investigational Product 
Study product will be administered to subjects by an unblinded study vaccine administrator via 
IM injection at all dosing times according to subject treatment assignment and as described in 
Section 6.2. Thus, subject compliance is not anticipated to be an issue. Deviations from the dose 
schedule may only occur as described in Section 6.3. 


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6.6 
Concomitant Medications/Treatments 
Administration of any medications, therapies, or vaccines will be recorded on the appropriate 
data collection form. Concomitant medications will include all current medications and 
medications taken in the 60 days prior to signing the informed consent form through 
approximately 21 days after the last study vaccination or early termination (if prior to 21 days 
after the last study vaccination), whichever occurs first. Medications reported in the electronic 
case report form (eCRF) are limited to those taken within 30 days prior to the first study 
vaccination through approximately 21 days after the last study vaccination. Prescription and 
over-the-counter drugs will be included as well as herbals, vitamins, and supplements. In 
addition, receipt of non-study influenza vaccines will be solicited through approximately 180 
days after the last study vaccination, and reported in the eCRF. Use of a new medication should 
prompt evaluation for the occurrence of any MAAE, including a new diagnosis of chronic 
medical disease or condition. 
Medications that might interfere with the evaluation of the investigational product(s) should not 
be used during the trial-reporting period (approximately 12 months after the last study 
vaccination) unless clinically indicated as part of the subject’s health care. Medications in this 
category include the prohibited medications per the Subject Exclusion Criteria (see Section 
5.1.2). In addition, the site principal investigator or appropriate sub-investigator may identify 
other medications that should not be used due to a risk to subject safety or assessment of 
reactogenicity and immunogenicity. 


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7 
STUDY PROCEDURES AND EVALUATIONS 
7.1 
Clinical Evaluations 
Complete medical history will be obtained by interview of subjects at the screening visit 
(optional) or on Day 1 prior to the first study vaccination. Subjects will be queried regarding a 
history of significant medical disorders of the head, eyes, ears, nose, throat, mouth, 
cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, urologic system, 
nervous system, blood, lymph nodes, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract. A history of any allergies, cancer, immunodeficiency, psychiatric 
illness, substance abuse, and autoimmune disease will be solicited. Subjects will also be queried 
regarding a personal history and family history of narcolepsy. At follow-up visits after the first 
study vaccination, an interim medical history will be obtained by interview of subjects noting 
any changes since the previous clinic visit or contact. The interim medical history should include 
an assessment for new medical conditions and symptoms suggestive of PIMMCs. 
Concomitant medications will be collected as described in Section 6.6. 
At the screening visit (optional) or the baseline visit (Day 1) a physical examination will be 
performed on all subjects to include the following organs and organ systems: including skin, 
head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, and nervous system, by a 
study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site 
principal investigator or sub-investigator. At follow-up visits after the first study vaccination, a 
targeted physical examination may be performed, if indicated based on the subject’s interim 
medical history, by a study clinician licensed to make medical diagnoses and listed on the Form 
FDA 1572 as the site principal investigator or sub-investigator. Targeted physical examinations 
should also include an assessment for signs suggestive of PIMMCs. 
Vital signs (oral temperature, pulse, and blood pressure) will be collected at the screening visit 
(optional) and prior to each study vaccination (Days 1 and 22). Vital signs assessed on Day 1 
prior to the first study vaccination will be considered as baseline. Subjects must not eat or drink 
anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
Height and weight will be collected at the screening visit (optional) or on Day 1 prior to the first 
study vaccination for the calculation of Body Mass Index (BMI). 
Reactogenicity assessments will include an assessment of solicited AEs occurring from the time 
of each study vaccination through Day 8 after each study vaccination, which includes an 
assessment of injection site reactions including pruritus (itching), ecchymosis (bruising), 
erythema (redness), induration (hardness), swelling, pain, and tenderness as well as systemic 


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reactions including fever, feverishness (chills/shivering/sweating), fatigue (tiredness), malaise 
(general unwell feeling), myalgia (body aches/muscular pain exclusive of the injection site), 
arthralgia (joint pain exclusive of the injection site), headache, and nausea. Pre-administration 
reactogenicity assessments will be performed prior to each study vaccination to establish 
baseline, then the study vaccination will be given. 
Subjects will be observed in the clinic for at least 20 minutes after each study vaccination. The 
study vaccination site will be examined, post-administration reactogenicity assessments will be 
performed, and any AE/SAEs will be recorded on the appropriate data collection form prior to 
discharge from the clinic. The study vaccination site will also be examined approximately 7 days 
after each study vaccination. 
All subjects will complete a subject memory aid from the time of each study vaccination through 
7 days after each study vaccination. Subject memory aids will be reviewed with the subjects for 
AEs (solicited injection site and systemic reactions and unsolicited AEs) approximately 3 and 7 
days after each study vaccination via phone call (Day 4) and clinical visit (Day 8). 
7.2 
Laboratory Evaluations 
7.2.1 
Clinical Laboratory Evaluations 
Urine or serum pregnancy tests will be performed locally by site laboratory at the screening visit 
(optional) and within 24 hours prior to each study vaccination on all women of childbearing 
potential. Results must be negative and known prior to randomization on Day 1 and 
administration of each study vaccination to be eligible for participation in this trial and receipt of 
each study vaccination. Erythrocyte sedimentation rate (ESR) will be collected from each subject 
at screening (optional) (within 28 days prior to the first study vaccination) or on Day 1 prior to 
study vaccination to confirm trial eligibility. To be eligible for participation in this trial and 
receipt of the first study vaccination, the subject’s ESR evaluation must be confirmed to meet the 
eligibility criteria as outlined in the Subject Inclusion Criteria (see Section 5.1.1). 
• The ESR evaluation will be performed locally by the site. A venous blood sample 
(approximately 4 mL) will be collected from each subject at the baseline visit. 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, Cr) will be collected from 
each subject prior to each study vaccination and approximately 7 days after each study 
vaccination. These evaluations will be performed by the central (clinical) laboratory. Venous 
blood samples (approximately 10 mL) will be collected for these safety labs. The results from the 
clinical safety laboratory parameters collected on Day 1 will not be available or reviewed prior to 
study vaccination, and will serve as a safety baseline assessment only. 


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The volume of venous blood to be collected for ESR as well as clinical safety laboratory 
evaluations is presented in Table 2. 
7.2.2 
Special Assays or Procedures 
Immunogenicity 
Assays to determine serum levels of HAI and Neut antibodies will be performed at Southern 
Research. Venous blood samples (approximately 10 mL) for antibody assays will be collected 
from each subject immediately prior to each study vaccination (Day 1 and approximately Day 
22) and, approximately 7 days after each study vaccination (approximately Day 8 and Day 29), 
and approximately 21 days and 180 days after the second study vaccination (approximately Days 
43 and 202). Subjects who withdraw early will have HAI and Neut antibody assays run on 
available sera. 
Venous blood samples (10 mL) will also be collected for future use at the same time points. Sites 
may elect to allow subjects to consent to study participation but to have the option to opt out of 
the collection of the future use samples, or may include collection of future use samples as a 
condition of study participation and not allow the opt out option.  
The assays for determination of the NA content and antibodies to the NA are under development. 
If successful, the correlation of NA content in the 2017 H7N9 IIV with elicited N9 NA specific 
serum antibody responses may be assessed; no additional venous blood will be collected from 
subjects.  2017 H7N9 IIV and Adjuvant will be shipped from the DMID CMS to the NA content 
assay designated laboratory for NA content assessment. Any laboratory involved with the 
determination of NA content or NA specific antibody responses will remain blinded to the HAI 
and Neut antibodies results performed at Southern Research. 
Samples for interim immunogenicity assessments (for HAI and Neut antibody assays) will be 
shipped from the DMID CMS to Southern Research for post-study vaccination immunogenicity 
assessment at Visit 03, 06, and 07 once available for the first 25 subjects per adjuvanted 
treatment arm and 13 subjects per unadjuvanted treatment arm in the 19-64 year-old age stratum 
and the first 15 subjects per adjuvanted treatment arm and 8 subjects per unadjuvanted treatment 
arm within the ≥65 year-old age stratum. Following the last subject’s Visit 7, samples for all 
subjects for visits through Visit 7 (Day 43) will be shipped to Southern Research for the final 
HAI and Neut analysis. For subjects included in the interim assessments new samples will be 
shipped and tested for the final analysis. Following the last subject’s visit 10, samples from all 
subjects for visit 10 (Day 202) will be shipped to Southern Research for the final HAI and Neut 
analysis. 


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The volume of venous blood to be collected for immunogenicity assays and future research is 
presented in Table 2. 


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Table 2: Venipuncture Volumes (mL): 
Study Visit 
Number 
V00 
V01 
V03 
V04 
V06 
V07 
V10 
Total 
(mL) 
Study Day post 
first study 
vaccination 
Screening 
(Optional)  
D -28 to -1 
Enrollment 
and Dose 1 
D1 
D8+2d 
D22+7d 
D29 
D43 
D202 
Study Day post 
second study 
vaccination 
 
 
 
Dose 2 
D1 
D8±3d 
D22+7d 
D181±14d 
Study Vaccination 
 
X 
 
X 
 
 
 
 
ESR 
4^ 
4^* 
 
 
 
 
 
4  
Clinical Baseline 
and Safety 
Laboratory 
Evaluations~ 
  
10† 
10 
10† 
10 
 
 
40  
Immunogenicity 
Assays 
  
10† 
10 
10† 
10 
10 
10 
60 
Serum Sample for 
Future Research# 
 
10† 
10 
10† 
10 
10 
10 
60 
Total (mL) 
(0) 4 
(34) 30 
30 
30 
30 
20 
20 
164 
^ Drawn up to 28 days prior to study vaccination. Results must be known and confirmed to meet the eligibility 
criterion prior to randomization and first study vaccination.   
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the collection 
of the future use samples, or may include collection of future use samples as a condition of study participation and 
not allow the opt out option.  
† All blood drawn immediately prior to study vaccination. 
* Not required if done at the optional screening visit 
7.2.3 
Specimen Preparation, Handling, and Shipping 
7.2.3.1 
Instructions for Specimen Preparation, Handling, and Storage 
Instructions for specimen preparation, handling, and storage are included in the central (clinical) 
laboratory manual and protocol-specific MOP as appropriate. 


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7.2.3.2 
Specimen Shipment 
Specimen shipment will occur at intervals during the course of this trial following all applicable 
International Air Transport Association (IATA) requirements and according to the specifics for 
storage temperature and documentation as detailed in the central (clinical) laboratory manual and 
protocol-specific MOP as appropriate. 
Specimens for safety laboratory evaluations will be shipped from the participating VTEU sites to 
the central (clinical) laboratory. 
Specimens for HAI and Neut antibody assays will be shipped from the participating VTEU sites 
to the DMID CMS, and then provided by the DMID CMS to Southern Research in a blinded 
manner. 
Specimens for the NA antibody assays will be shipped from the participating VTEU sites to the 
DMID CMS, and then provided by the DMID CMS to the NA antibody assay laboratory once it 
has been identified. 
Further instructions for specimen shipment are included in the central (clinical) laboratory 
manual and protocol-specific MOP, as appropriate. 


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8 
STUDY SCHEDULE 
Complete study schedule details listed by type of visit are described below. Refer also to 
Sections 4 and 7 and Appendix A: Schedule of Study Procedures and Evaluations. 
8.1 
Screening (Optional) and Enrollment Visits 
8.1.1 
Visit 00, Screening Clinic Visit (Optional) (Day -28 to -1) 
• Subjects will be provided with a description of this trial (purpose and study procedures) 
and asked to read and sign the informed consent form. The informed consent form will be 
signed prior to performing any study procedures, including administration of the first 
study vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Eligibility criteria will be reviewed with subjects. 
• Complete medical history will be obtained by interview of subjects to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the informed consent 
form will be reviewed with subjects to determine stability of chronic diseases and 
eligibility. Medications reported in the eCRF are limited to those taken within 30 days 
prior to the first study vaccination.  
• Subject receipt of licensed seasonal influenza vaccine over the previous two seasons, 
what type (inactivated or live attenuated), and approximate date of vaccination will be 
recorded on the appropriate data collection form, if known. Prior receipt of licensed 
seasonal influenza vaccine is not exclusionary, as long as it has been administered within 
the allowable window (see Section 5.1.2). 
 
• Subject receipt of non-seasonal influenza vaccines, including those that are experimental, 
what type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known. Prior 
receipt of non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 
vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to first study vaccination. Subjects must not eat or drink anything 
hot or cold, or smoke within 10 minutes prior to taking oral temperature. 


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• Height and weight will be collected for the calculation of BMI. 
• A physical examination will be performed on all subjects to include the following organs 
and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 
nodes, abdomen, general appearance, musculoskeletal  and nervous system and as 
assessment for signs suggestive of a PIMMC, by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or 
sub-investigator. 
• A urine or serum pregnancy test may be performed on all women of childbearing 
potential. Results must be negative to ensure eligibility. 
• Approximately 4 mL of venous blood will be collected for ESR, and performed locally 
by the site. The ESR value must be confirmed as less than 30 mm per hour prior to 
randomization and first study vaccination. 
8.1.2 
Visit 01 Day 01, Enrollment (for subjects previously screened at Day -28 to -1) 
and First Vaccination (Dose 1), Clinic Visit   
• Subject’s willingness to participate will be reconfirmed and documented in the subject’s 
study records prior to performing any further study procedures, including administration 
of the first study vaccination. 
• Eligibility criteria, including results of the ESR will be reviewed.  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the study vaccination and any changes since the previous clinic visit or 
contact will be noted. 
• All concomitant medications will be reviewed with subjects prior to the first study 
vaccination for accuracy and completeness. Any new concomitant medications taken 
since the screening visit will be reviewed with subjects and assessed for continued 
eligibility prior to the first study vaccination.  
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to first study vaccination. Vital signs assessed on Day 1 prior to 
the first study vaccination will be considered as baseline. Subjects must not eat or drink 
anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 


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• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed prior to the first study vaccination, if indicated based on 
review of complete medical history and any updates obtained by interview of subjects 
since the screening visit, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site principal investigator or sub-investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the first study 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first study vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
study vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
study vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr), 
and performed by the central (clinical) laboratory. The results from this blood draw will 
not be available or reviewed prior to study vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to study vaccination for 
future research from subjects who consent to collection of serum for future use, either by 
signing an informed consent form that includes collection of future use samples as a 
condition of study participation or by indicating that they opt in to sample collection for 
future use if the informed consent form allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The site of injection (right or left arm) and time of 
administration will be recorded on the appropriate data collection form. Subjects will be 
observed in the clinic for at least 20 minutes after the first study vaccination. The first 
study vaccination site will be examined, post-administration reactogenicity assessments 
will be performed, and any AE/SAEs will be recorded on the appropriate data collection 
form prior to discharge from the clinic.  
• Subjects will be provided with a memory aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited 


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AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the first study vaccination. If the site principal 
investigator or appropriate sub-investigator deems the reaction severe enough, further 
instructions will be given to the subject on the proper course of action, including a return 
to the clinic for immediate evaluation if appropriate. 
8.1.3 
Visit 01, Day 1, Enrollment/Baseline (for subjects not previously screened at Day 
-28 to -1) and First Study Vaccination (Dose 1), Clinic Visit 
• Subjects will be provided with a description of this trial (purpose and study procedures) 
and asked to read and sign the informed consent form. The informed consent form will be 
signed prior to performing any study procedures, including administration of the first 
study vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Complete medical history will be obtained by interview of subjects prior to the first study 
vaccination to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the informed consent 
form will be reviewed with subjects. Medications reported in the eCRF are limited to 
those taken within 30 days prior to the first study vaccination. 
• Subject receipt of licensed seasonal influenza vaccine over the previous two seasons, 
what type (inactivated or live attenuated), and approximate date of vaccination will be 
recorded on the appropriate data collection form, if known. Prior receipt of licensed 
seasonal influenza vaccine is not exclusionary, as long as it has been administered within 
the allowable window (see Section 5.1.2).Subject receipt of non-seasonal influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known. Prior receipt of non-seasonal influenza 
vaccines are not exclusionary, except influenza A/H7 vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to first study vaccination. Vital signs assessed on Day 1 prior to 
the first study vaccination will be considered as baseline. Subjects must not eat or drink 
anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 


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• Height and weight will be collected prior to the first study vaccination for the calculation 
of BMI. 
• A physical examination will be performed on all subjects to include the following organs 
and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 
nodes, abdomen, general appearance, musculoskeletal and nervous system and as 
assessment for signs suggestive of a PIMMC, by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or 
sub-investigator. 
• Approximately 4 mL of venous blood will be collected for ESR, and performed locally 
by the site. The ESR value must be confirmed as less than 30 mm per hour prior to 
randomization and first study vaccination. 
• Eligibility criteria, including results of ESR evaluation, will be reviewed with subjects 
prior to the first study vaccination to ensure continued eligibility. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the first study 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first study vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
study vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
study vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr), 
and performed by the central (clinical) laboratory. The results from this blood draw will 
not be available or reviewed prior to study vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to study vaccination for 
future research from subjects who consent to collection of serum for future use, either by 
signing an informed consent form that includes collection of future use samples as a 
condition of study participation or by indicating that they opt in to sample collection for 
future use if the informed consent form allows the option to choose that option. 


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• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The site of injection (right or left arm) and time of 
administration will be recorded on the appropriate data collection form. Subjects will be 
observed in the clinic for at least 20 minutes after the first study vaccination. The first 
study vaccination site will be examined, post-administration reactogenicity assessments 
will be performed, and any AE/SAEs will be recorded on the appropriate data collection 
form prior to discharge from the clinic. 
• Subjects will be provided with a memory aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the first study vaccination. If the site principal 
investigator or appropriate sub-investigator deems the reaction severe enough, further 
instructions will be given to the subject on the proper course of action, including a return 
to the clinic for immediate evaluation if appropriate. 
8.2 
Follow-up Visits 
Follow-up visits are scheduled in reference to study vaccination dates as indicated for each visit 
window. 
8.2.1 
Visit 02, Day 4, Memory Aid Review, Phone Call 
(Window: Day 4±1 day post first study vaccination) 
Study personnel will contact subjects by phone to solicit any AE/SAE, medical history, and 
concomitant medication information (including solicitation for receipt of any non-study 
influenza vaccines, including those that are experimental, what type (inactivated or live 
attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected.) and review 
information on their memory aid. Based on the information, subjects may be asked to return to 
the clinic for evaluation. 
  
8.2.2 
Visit 03, Day 8, Clinic Visit 
(Window: Day 8+2 days post first study vaccination) 


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• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected.) will be 
recorded on the appropriate data collection form. 
• All AE/SAEs will be recorded on the appropriate data collection form.  
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The first study vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs, WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use, either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or 
by indicating that they opt in to sample collection for future use if the informed consent 
form allows the option to choose that option. 
8.2.3 
Visit 04, Day 22, Second Study Vaccination (Dose 2), Clinic Visit 
(Window: Day 22+7 days post first study vaccination) 
• Eligibility criteria will be reviewed with subjects prior to the second study vaccination to 
ensure continued eligibility. 
• For a subject to receive the second study vaccination, refer to section 5.2.3 for second 
vaccination eligibility criteria.   


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• Interim medical history, including an assessment for new medical conditions stability of 
chronic diseases and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the second study vaccination and any changes since the previous clinic 
visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected. Prior receipt of 
non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 vaccines 
(see Section 5.1.2)will be recorded on the appropriate data collection form prior to the 
second study vaccination. 
• All AE/SAEs will be recorded on the appropriate data collection form.  
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained prior 
to the second study vaccination. Subjects must not eat or drink anything hot or cold, or 
smoke within 10 minutes prior to taking oral temperature. Note: Vital signs are not 
required for subjects who are discontinued from receipt of the second study vaccination 
and are being followed for safety. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed prior to the second study vaccination, if indicated based on 
review of interim medical history, by a study clinician licensed to make medical 
diagnoses and listed on the Form FDA 1572 as the site principal investigator or sub-
investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the second 
study vaccination on all women of childbearing potential. Results must be negative and 
known prior the second study vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the second study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected for safety labs WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected immediately prior to the second 
study vaccination for serum antibody assays. 


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• Approximately 10 mL of venous blood will be collected immediately prior to the second 
study vaccination for future research from subjects who consent to collection of serum 
for future use, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The second study vaccination may be given in the same 
preferred arm as long as there is no interference with the reactogenicity assessment. The 
site of injection (right or left arm) and time of administration will be recorded on the 
appropriate data collection form. Subjects will be observed in the clinic for at least 20 
minutes after the second study vaccination. The second study vaccination site will be 
examined, post-administration reactogenicity assessments will be performed, and any 
AE/SAEs will be recorded on the appropriate data collection form prior to discharge from 
the clinic. 
• Subjects will be provided with a memory aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the second study vaccination. If the site principal 
investigator or appropriate sub-investigator deems the reaction severe enough, further 
instructions will be given to the subject on the proper course of action, including a return 
to the clinic for immediate evaluation if appropriate. 
8.2.4 
Visit 05, Day 25, Memory Aid Review, Phone Call 
(Window: Day 4+1 day post second study vaccination) 
Study personnel will contact subjects by phone to solicit any AE/SAE, medical history, and 
concomitant medication information (including solicitation for receipt of any non-study 
influenza vaccines, including those that are experimental, what type (inactivated or live 
attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected.) and review 
information on their memory aid. Based on the information, subjects may be asked to return to 
the clinic for evaluation. Note: For subjects who are discontinued from the receipt of the second 
study vaccination, AEs will be limited to SAEs, MAAEs, including NOCMCs, and PIMMCs. 


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8.2.5 
Visit 06, Day 29, Clinic Visit 
(Window: Day 8+2 days post second study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected.) will be 
recorded on the appropriate data collection form. 
• All AE/SAEs will be recorded on the appropriate data collection form. Note: for subjects 
who discontinued from the receipt of the second study vaccination, AEs will be limited to 
SAEs, MAAEs, including NOCMCs, and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The second study vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use, either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or 
by indicating that they opt in to sample collection for future use if the informed consent 
form allows the option to choose that option. 
8.2.6 
Visit 07, Day 43, Clinic Visit 
(Window: Day 22+7 days post second study vaccination) 


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• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected.) will be 
recorded on the appropriate data collection form. 
• All AE/SAEs will be recorded on the appropriate data collection form. Note: for subjects 
who discontinued from the receipt of the second study vaccination, AEs will be limited to 
SAEs, MAAEs, including NOCMCs, and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for HAI and Neut antibody 
assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use, either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or 
by indicating that they opt in to sample collection for future use if the informed consent 
form allows the option to choose that option. 
8.2.7 
Visit 08, Day 82, Safety Follow-up, Phone Call 
(Window: Day 61±7 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events and solicitation for receipt of any 
non-study influenza vaccines , including those that are experimental, what type (inactivated or 
live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination 
will be recorded on the appropriate DCF, if known and not previously collected. Adverse events 
limited to MAAEs including NOCMCs, PIMMCS, and SAEs that have occurred since the 
previous clinic visit or contact will be solicited. Based on the information, subjects may be asked 
to return to the clinic for evaluation. 


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8.2.8 
Visit 09, Day 142, Safety Follow-up, Phone Call 
(Window: Day 121±14 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events and solicitation for receipt of any 
non-study influenza vaccines, including those that are experimental, what type (inactivated or 
live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination 
will be recorded on the appropriate DCF, if known and not previously collected. Adverse events 
limited to MAAEs including NOCMCs, PIMMCs, and SAEs that have occurred since the 
previous clinic visit or contact will be solicited. Based on the information, subjects may be asked 
to return to the clinic for evaluation. 
8.2.9 
Visit 10, Day 202, Safety Follow-up, Clinic Visit 
(Window: Day 181±14 days post second study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 
interview of subjects and any changes since the previous clinic visit or contact will be 
noted. 
• Receipt of any non-study influenza vaccines, including those that are experimental, what 
type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known and 
not previously collected will be solicited. 
• Adverse events limited to MAAEs including NOCMCs, PIMMCs, and SAEs that have 
occurred since the previous clinic visit or contact will be solicited  
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use, either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or 
by indicating that they opt in to sample collection for future use if the informed consent 
form allows the option to choose that option.  


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8.2.10 
Visit 11, Day 387, Safety Follow-up, Phone Call 
(Window: Day 366±14 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events. AEs limited to MAAEs including 
NOCMCs, and PIMMCS, and SAEs that have occurred since the previous clinic visit or contact 
will be solicited. Based on the information, subjects may be asked to return to the clinic for 
evaluation. 
8.2.11 
Early Termination Visit (if needed) 
The following activities will be performed at the early termination visit on subjects who 
withdraw, or are withdrawn or terminated from this trial: 
• Interim medical history, including an assessment for new medical conditions and 
symptoms suggestive of PIMMCs, will be obtained by interview of subjects and any 
changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects (if within 7 days after the last 
study vaccination). 
• All concomitant medications will be recorded on the appropriate data collection form (if 
within 21 days after the last study vaccination). Receipt of any non-study influenza 
vaccine, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected will be recorded 
if within 180 days after the second study vaccination. 
• All AE/SAEs will be recorded on the appropriate data collection form. AEs will be 
limited to SAEs, MAAEs, including NOCMCs, and PIMMCs that have occurred since 
the previous clinic visit or contact will be solicited (if after 21 days after last study 
vaccination).  
• Vital signs, including oral temperature, pulse, and blood pressure, may be obtained if 
indicated. Subjects must not eat or drink anything hot or cold, or smoke within 10 
minutes prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 


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• The study vaccination site will be examined (if within 7 days after the last study 
vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
the last study vaccination). 
• Approximately 10 mL of venous blood will be collected for WBC, Hgb, PLT, ALT, T. 
Bili, Cr, and performed by the central (clinical) laboratory (if within 7 days after the last 
study vaccination). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if 
within 21 days after the last study vaccination). 
• Approximately 10 mL of venous blood will be collected for future research (if within 21 
days after the last study vaccination) from subjects who consent to collection of serum for 
future use, either by signing an informed consent form that includes collection of future 
use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option.  
8.2.12 
Unscheduled Visit (if needed) 
Unscheduled visits may occur at any time during this trial. Any of the following activities may 
be performed: 
• Interim medical history, including an assessment for new medical conditions and 
symptoms suggestive of PIMMCs, will be obtained by interview of subjects and any 
changes since the previous clinic visit or contact will be noted (if indicated). 
• Memory aid information will be reviewed with subjects (if within 7 days after the last 
study vaccination). 
• All concomitant medications will be recorded on the appropriate data collection form (if 
within 21 days after the last study vaccination). Receipt of any non-study influenza 
vaccine, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected will be recorded 
if within180 days after the second study vaccination. 


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• All AE/SAEs will be recorded on the appropriate data collection form. AEs will be 
limited to SAEs, MAAEs, including NOCMCs, and PIMMCs if after 21 days after the 
last study vaccination. 
• Vital signs, including oral temperature, pulse, and blood pressure, may be obtained if 
indicated. Subjects must not eat or drink anything hot or cold, or smoke within 10 
minutes prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The study vaccination site will be examined (if within 7 days after the last study 
vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
the last study vaccination). 
• Approximately 10 mL of venous blood will be collected for WBC, Hgb, PLT, ALT, T. 
Bili, Cr, and performed by the central (clinical) laboratory (if indicated). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if 
within 21 days after the last study vaccination). 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use (if within 21 days after the last study 
vaccination), either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 


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9 
ASSESSMENT OF SAFETY 
9.1 
Specification of Safety Parameters 
Safety will be assessed by the frequency and severity of: 
1. SAEs occurring from the time of the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study vaccination 
through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, induration/swelling, 
pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, arthralgia, 
headache, and nausea. 
3. Clinical safety laboratory AEs occurring from the time of each study vaccination through 
approximately 7 days after each study vaccination. Parameters to be evaluated include 
WBC, Hgb, PLT, ALT, T. Bili, Cr. 
4. Unsolicited AEs –non-serious AEs occurring from the time of each study vaccination 
through approximately 21 days after each study vaccination. 
5. MAAEs, including NOCMCs, and PIMMCs occurring from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
9.2.1 
Adverse Events 
Adverse Event (AE): (ICH) E6 defines an AE as any untoward medical occurrence in a patient 
or clinical investigation subject administered a pharmaceutical product regardless of its causal 
relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product. The occurrence of an AE may come to the attention 
of study personnel during study visits and interviews of a study recipient presenting for medical 
care, or upon review by a study monitor. 


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AEs, including solicited injection site and systemic (subjective and quantitative) reactions, not 
meeting the protocol-defined criteria for SAEs will be captured on the appropriate data collection 
form and eCRF. Information to be collected for unsolicited non-serious AEs includes event 
description, date of onset, licensed study clinician’s assessment of severity and relationship to 
study product and alternate etiology (if not related to study product) (assessed only by those with 
the training and authority to make a diagnosis and listed on the Form FDA 1572 as the site 
principal investigator or sub-investigator), date of resolution of the event, seriousness, and 
outcome. AEs occurring during the trial collection and reporting period will be documented 
appropriately regardless of relationship. AEs will be followed through resolution. 
Any medical condition that is present at the time that the subject is screened will be considered 
as baseline and not reported as an AE. However, if the severity of any pre-existing medical 
condition increases, it will be recorded as an AE. 
AEs must be graded for severity and assessed for relationship to study product (see definitions 
below). AEs characterized as intermittent require documentation of onset and duration of each 
episode. The start and stop date of each reported AE will be recorded on the appropriate data 
collection form and eCRF. 
FDA defines an AE as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
New-Onset Chronic Medical Conditions (NOCMCs): NOCMCs are defined as any new ICD-
10 diagnosis that is applied to the subject during the duration of the study, after receipt of the 
study agent, that is expected to continue for at least 3 months and requires continued health care 
intervention. 
Medically-Attended Adverse Events (MAAEs): For each unsolicited AE experienced, the 
subject will be asked if he/she had received medical attention, defined as hospitalization, an 
emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any 
reason. AEs characterized by such unscheduled medical care will be designated as MAAEs. 
Potentially Immune-Mediated Medical Conditions (PIMMCs): PIMMCs constitute a group 
of AEs that includes diseases which are clearly autoimmune in etiology and other inflammatory 
and/or neurologic disorders which may or may not have autoimmune etiologies. PIMMCs 
currently in effect are presented in Appendix B: List of PIMMCs. 
Severity of Event: AEs will be assessed by a licensed study clinician listed on the Form FDA 
1572 as the site principal investigator or appropriate sub-investigator using a protocol-defined 
grading system (see Sections 9.2.2 and 9.2.3). For events not included in the protocol-defined 
grading system, the following guidelines will be used to quantify severity: 


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• 
Mild (Grade 1): Events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
• 
Moderate (Grade 2): Events result in a low level of inconvenience or concern with 
therapeutic measures. Moderate events may cause some interference with functioning and 
daily activities. 
• 
Severe (Grade 3): Events interrupt the subject’s daily activities and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
Relationship to Study Product: The licensed study clinician’s assessment of an AE's 
relationship to study product is part of the documentation process, but it is not a factor in 
determining what is or is not reported in this trial. If there is any doubt as to whether a clinical 
observation is an AE, the event should be reported. The relationship to study product must be 
assessed for AEs using the terms: related or not related. In a clinical trial, the study product must 
always be suspect. To help assess, the following guidelines are used: 
• Related – There is a reasonable possibility that the study product caused the AE. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event. 
9.2.2 
Reactogenicity 
Reactogenicity events are AEs that are common and known to occur following administration of 
this type of study vaccine. The following Toxicity Grading Scales will be used to grade solicited 
local (injection site) and systemic (subjective and quantitative) reactions: 
Injection Site Reactogenicity Grading 
Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain – experienced 
without touching the 
injection site 
(spontaneous discomfort) 
Subject is aware of pain, 
but it does not interfere 
with daily activity, and 
no pain medication is 
taken 
Subject is aware of pain; 
there is interference with 
daily activity or it 
requires repeated use of a 
non-narcotic pain reliever 
for >24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or requires any use 
of a narcotic pain reliever 


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Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Tenderness – hurts only 
when injection site is 
touched or the arm is 
moved 
The area immediately 
surrounding the injection 
site hurts only when 
touched or with arm 
motion, and it does not 
interfere with daily 
activity 
The area immediately 
surrounding the injection 
site hurts when touched or 
with arm motion, and it 
interferes with daily 
activity 
The area immediately 
surrounding the injection 
site hurts when touched or 
with arm motion, and it 
prevents daily activity 
Pruritus (Itching) 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Ecchymosis (Bruising)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Erythema (Redness)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Induration 
(Hardness)/Swelling* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
* Will also be measured in mm but size will not be used as halting criteria. 
 
Ecchymosis, erythema, and induration/swelling as analyzed by measurement will be graded as 
follows: 
Local (Injection Site) Reactogenicity Measurements 
Local (Injection Site) Reaction 
Small 
Medium 
Large 
Ecchymosis (Bruising)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Erythema (Redness)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Induration (Hardness)/Swelling* 
<20 mm 
20 mm – 50 mm 
>50 mm 
* Will not be used as halting criteria. 
Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverishness 
(Chills/Shivering/Sweating) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 


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Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Fatigue (Tiredness) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Malaise (General Unwell 
Feeling) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Myalgia (Body 
Aches/Muscular Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Arthralgia (Joint Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Headache 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Nausea 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
* Not at injection site. 
 
Oral temperature# will be graded as follows: 
Quantitative Systemic Reactogenicity Grading 
Systemic (Quantitative) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Fever* - oral† 
38.0°C – 38.4°C 
100.4°F – 101.1°F 
38.5°C – 38.9°C 
101.2°F – 102.0°F 
>38.9°C 
>102.0°F 
# Oral temperature assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
* A fever can be considered not related to the study product if an alternative etiology can be documented. 
† Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
9.2.3 
Additional Adverse Event Severity Grading 
For Individuals 19-64 years of age, pulse and blood pressure# will be graded as follows: 
Physiologic Parameter 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Bradycardia - beats per minute 
45 – 46 
40 – 44 
<40 


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Tachycardia - beats per minute 
101 – 130 
131 – 155 
>155 
Hypotension (systolic) mmHg 
80 – 84 
75 – 79 
<75 
Hypotension (diastolic) mmHg 
50 – 54 
45 – 49 
<45 
Hypertension (systolic) mmHg 
151 – 155 
156 – 160 
>160 
Hypertension (diastolic) mmHg 
96 – 100 
101 – 105 
>105 
# Pulse and blood pressure assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
 
 


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For Individuals >65 years of age, pulse and blood pressure# will be graded as follows:  
Physiologic Parameter 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Bradycardia - beats per minute 
45 – 46 
40 – 44 
<40 
Tachycardia - beats per minute 
101 – 130 
131 – 155 
>155 
Hypotension (systolic) mm Hg 
80 – 84 
75 – 79 
<75 
Hypotension (diastolic) mm Hg 
50 – 54 
45 – 49 
<45 
Hypertension (systolic) mm Hg 
161 – 165 
166 – 170 
>170 
Hypertension (diastolic) mm Hg 
96 – 100 
101 – 105 
>105 
# Pulse and blood pressure assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
 
 


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Clinical safety laboratory results# will be graded as follows: 
Clinical Safety Laboratory Adverse Event Grading
# 
Hematology 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC 103/µL (Decrease) 
2.5 – 3.9 
1.5 – 2.4 
<1.5 
WBC 103/µL (Increase) 
10.6 – 15.0 
15.1 – 20.0 
>20.0 
Hgb g/dL (Decrease) (Female) 
10.1 – 11.4 
8.5 – 10 
<8.5 
Hgb g/dL (Decrease) (Male) 
11.0 – 12.4 
9.5 – 10.9 
<9.5 
Platelets 103/µL (Decrease) 
125 – 139 
100 – 124 
<100 
Platelets 103/µL (Increase) 
416 – 550 
551– 750 
>750 
 
 
 
 
Chemistry 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
ALT IU/L (Increase) (Female) 
44 – 100 
101 – 200 
>200 
ALT IU/L (Increase) (Male) 
61 – 138 
139 – 275 
>275 
Total Bilirubin mg/dL (Increase) – 
when accompanied by any increase in 
ALT 
1.30 – 1.59 
1.60 – 1.80 
>1.80 
Total Bilirubin mg/dL (Increase) – 
when ALT is normal 
1.30 – 1.89 
1.90 – 2.40 
>2.40 
Creatinine mg/dL (Increase) 
(Female) 
1.1 – 1.7 
1.8 – 2.0 
>2.0 
Creatinine mg/dL (Increase) (Male) 
1.4 – 1.7 
1.8 – 2.0 
>2.0 
# Clinical laboratory evaluations assessed on Day 1 prior to the first study vaccination will be considered as 
baseline. 
9.2.4 
Serious Adverse Events 
Serious Adverse Event (SAE): An AE or suspected adverse reaction is considered “serious” if, 
in the view of either the site principal investigator or sponsor, it results in any of the following 
outcomes: 
• Death, 
• A life-threatening AE*, 
• Inpatient hospitalization or prolongation of existing hospitalization, 


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• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
• A congenital anomaly/birth defect. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical 
judgment they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
* Life-threatening AE. An AE is considered “life-threatening” if, in the view of either the site 
principal investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an AE that, had it occurred in a more severe form, might have caused 
death. 
SAEs will be: 
• 
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• 
Recorded on the appropriate SAE form and eCRF. 
• 
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator. 
• 
Reviewed and evaluated by an Independent Safety Monitor (ISM) (as deemed necessary), 
the DSMB (periodic review unless related), DMID, and the IRB. 
9.2.5 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
The site principal investigator or appropriate sub-investigator is responsible for recording all 
AE/SAEs that are observed or reported during this trial, regardless of the relationship to study 
product. AE/SAEs, abnormal laboratory test values, or abnormal clinical findings will be 
collected, assessed, documented, reported, and followed appropriately, using a local laboratory 
as necessary. In determining eligibility, refer to section 5.2.3 and the protocol-specific MOP. 


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9.3 
Reporting Procedures 
Solicited injection site and systemic reactogenicity events will be documented and reported from 
the time of each study vaccination through 7 days after each study vaccination. 
Clinical safety laboratory AEs will be documented and reported from the time of each study 
vaccination through approximately 7 days after each study vaccination. 
Unsolicited non-serious AEs will be documented and reported from the time of each study 
vaccination through approximately 21 days after each study vaccination. 
SAEs, MAAEs, including NOCMCs, and PIMMCs will be documented and reported from the 
time of the first study vaccination through approximately 12 months after the last study 
vaccination. 
9.3.1 
Serious Adverse Events 
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group at the 
following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
 
 
 
In addition to the SAE form, selected SAE data fields must also be entered into 
AdvantageEDCSM. Please see the protocol-specific MOP for details regarding this procedure. 
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible. 
The site will send a copy of the SAE report(s) to the ISM (as deemed necessary) when they are 
provided to the DMID Pharmacovigilance Group. The DMID Medical Monitor and DMID 
Clinical Project Manager will be notified of the SAE by the DMID Pharmacovigilance Group. 
The DMID Medical Monitor will review and assess the SAE for regulatory reporting and 
potential impact on study subject safety and protocol conduct. 


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At any time after completion of this trial, if the site principal investigator or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the site 
principal investigator or appropriate sub-investigator will report the event to the DMID 
Pharmacovigilance Group. 
9.3.2 
Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND 
Following notification from the site principal investigator or appropriate sub-investigator, 
DMID, the Investigational New Drug (IND) sponsor, will report any suspected adverse reaction 
that is both serious and unexpected. DMID will report an AE as a suspected adverse reaction 
only if there is evidence to suggest a causal relationship between the drug and the AE. DMID 
will notify FDA and all participating site principal investigators (i.e., all principal investigators to 
whom the sponsor is providing drug under its IND(s) or under any principal investigator’s 
IND(s)) in an IND safety report of potential serious risks from clinical trials or any other source, 
as soon as possible, but in no case later than 15 calendar days after the sponsor determines that 
the information qualifies for reporting as specified in 21 CFR Part 312.32. DMID will also notify 
FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible, 
but in no case later than 7 calendar days after the sponsor’s initial receipt of the information. 
Relevant follow up information to an IND safety report will be submitted as soon as the 
information is available. Upon request from FDA, DMID will submit to FDA any additional data 
or information that the agency deems necessary, as soon as possible, but in no case later than 15 
calendar days after receiving the request. 
All serious events designated as “not related” to study product(s), will be reported to the FDA at 
least annually in a summary format. 
9.3.3 
Reporting of Pregnancy 
Pregnancies occurring in study subjects will be reported via AdvantageEDCSM on the Pregnancy 
Report form. No further study vaccinations will be administered to pregnant subjects, but with 
the subject’s permission all protocol-required venous blood samples will be obtained and the 
subject will continue to be followed for safety for the duration of this trial. Efforts will be made 
to follow all pregnancies reported during the course of this trial to pregnancy outcome pending 
the subject’s permission. 
9.4 
Type and Duration of Follow-up of Subjects after Adverse Events 
AEs will be collected, assessed, and followed through resolution from the time of each study 
vaccination through approximately 21 days after each study vaccination. 


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SAEs, MAAEs, including NOCMCs, and PIMMCs will be collected, assessed, and followed 
from the time of the first study vaccination through resolution even if this extends beyond the 
trial-reporting period (approximately 12 months after the last study vaccination). 
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
Follow-up procedures, evaluations, and outcomes will be recorded on the appropriate data 
collection form. 
9.5 
Halting Rules 
Further enrollment and study vaccinations will be halted for DSMB review/recommendation if 
any of the following are reported: 
• Any subject experiences ulceration, abscess, or necrosis at the injection site related to 
study product administration. 
• Any 2 or more subjects experience laryngospasm, bronchospasm, or anaphylaxis within 1 
day after administration of study product that is considered related to study product. 
• Three or more subjects experience generalized urticaria (defined as occurring at more 
than two body parts) within 3 days after administration of study product that is 
considered related to study product. 
• Any subject experiences a study vaccine-related SAE from the time of the first study 
vaccination through the subject’s last study visit. 
• Any subject experiences acute weakness of limbs and/or cranial nerve innervated muscles 
(description of potential signal of GBS) after administration of study product. 
• Any subject develops a PIMMC after administration of study product. 
This trial will also be halted for DSMB review/recommendation if, within 7 days after 
administration of either study vaccination, any of the following occurs within the AS03-
adjuvanted treatment arms or within the two unadjuvanted treatment arms.   
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administration, across all groups, 
experience the same severe (Grade 3) study vaccine-related injection site reaction. 


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Ecchymosis, erythema, and induration/swelling will also be measured in mm but size will 
not be used as halting criteria.  
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administration, across all groups, 
experience the same severe (Grade 3) study vaccine-related subjective systemic reaction, 
for which the severity (grade) is corroborated by study personnel. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administration, across all groups, 
experience the same severe (Grade 3) study vaccine-related quantitative systemic 
reaction. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administration, across all groups, 
experience the same severe (Grade 3) study vaccine-related clinical safety laboratory AE. 
Grading scales for solicited injection site and systemic (subjective and quantitative) reactions are 
included in Section 9.2.2. 
Grading scales for clinical safety laboratory AEs are included in Section 9.2.3. 
If any of the halting rules are met following any subject receipt of any study vaccination, then 
this trial will not continue with the remaining enrollments or study vaccinations without a review 
by and recommendation from the DSMB to proceed. 
DMID retains the authority to suspend additional enrollment and study interventions/ 
administration of study product during the entire trial, as applicable. 
The DMID Medical Monitor is empowered to stop enrollment and study vaccinations if AEs that 
meet the halting criteria are reported. 
9.6 
Safety Oversight 
9.6.1 
Independent Safety Monitor (ISM) 
The ISM is a physician with relevant expertise whose primary responsibility is to provide 
independent safety monitoring in a timely fashion. For this trial an ISM is not required. 
However, at each participating VTEU site, and at the request of DMID, in real time, the principal 
investigator should be able to identify an independent physician to function as an ad hoc ISM. 


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That person should have the privileges to examine the subject, review the subject’s medical and 
study records, and provide an independent medical assessment and recommendation to DMID. 
9.6.2 
Data and Safety Monitoring Board (DSMB) 
Safety oversight will be conducted by a DSMB that is an independent group of experts that 
monitors subject safety and advises DMID. The DSMB members will be separate and 
independent of study personnel participating in this trial and should not have scientific, financial 
or other conflict of interest related to this trial. The DSMB will consist of members with 
appropriate expertise to contribute to the interpretation of the data from this trial. The DSMB 
will operate under the rules of a DMID-approved charter that will be written at the organizational 
meeting of the DSMB. Procedures for DSMB reviews/meetings will be defined in the charter. 
Reports may include enrollment and demographic information, medical history, concomitant 
medications, physical assessments, clinical laboratory values, dosing compliance, and solicited 
and unsolicited AE/SAEs, HAI and Neut antibody assay results. The DSMB will review SAEs 
on a regular basis and ad hoc during this trial. The DMID Medical Monitor and the ISM (as 
deemed necessary) will be responsible for reviewing SAEs in real time.  
The DSMB will conduct the following reviews: 
• Bi-monthly safety data reviews (including monthly safety data and cumulative safety 
data) until the last subject completes the visit that occurs approximately 21 days after the 
last study vaccination.  
• Interim analysis of serum antibody responses comparing venous blood samples collected 
at baseline, Visit 03, Visit 06, and Visit 07 for 25 subjects per adjuvanted treatment arm 
and 13 subjects per unadjuvanted treatment arm within the 19-64year-old stratum, and 
the first 15 subjects per adjuvanted treatment arm and 8 subjects per unadjuvanted 
treatment arm within the ≥65 year-old stratum. These reviews may be conducted as part 
of the scheduled monthly reviews or as the data become available. Reports will include 
data summarized by unblinded treatment arm, but the presentation will be in a format that 
prevents inadvertent unblinding of any individual subjects.  
• Data review 9 days after all subjects have received Dose 2 (complete study visit number 
V06). This review may be conducted as part of the scheduled monthly reviews.  
• Ad hoc when a halting rule is met or DMID/DSMB chair may convene an ad hoc meeting 
if there are immediate concerns regarding observations during the course of this trial. 
• Final review meeting may be held 6 to 8 months after clinical database lock to review the 
cumulative unblinded safety and immunogenicity data for this trial. If a final review 


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meeting is held, the data will be provided in a standard summary format. The DSMB may 
be asked to provide recommendations in response to questions posed by DMID. 
Additional data may be requested by the DSMB, and interim statistical reports may be generated 
as deemed necessary and appropriate by DMID. The DSMB may receive data in aggregate and 
presented by treatment arm. The DSMB may also be provided with expected and observed rates 
of the expected AEs in an unblinded fashion, and may request the treatment assignment be 
unblinded for an individual subject if required for safety assessment. The DSMB will review 
grouped and unblinded data in the closed session only. As an outcome of each review/meeting, 
the DSMB will make a recommendation as to the advisability of proceeding with study 
vaccinations (as applicable), and to continue, modify, or terminate this trial. 
The DSMB will operate under the rules of a DMID-approved charter that will be written at the 
organizational meeting of the DSMB. At this time, each data element that the DSMB needs to 
assess will be clearly defined. Procedures for DSMB reviews/meetings will be defined in the 
charter. The DSMB will review applicable data to include, but not limited to, study progress and 
participant, clinical, safety and reactogenicity data. Reports may include enrollment and 
demographic information, medical history, concomitant medications, physical assessments, 
clinical laboratory values, dosing compliance, and solicited and unsolicited AE/SAEs, HAI and 
Neut antibody assay results. 
DMID or the DSMB chair may convene the DSMB on an ad hoc basis according to protocol 
criteria or if there are immediate concerns regarding observations during the course of this trial. 
The DMID Medical Monitor is empowered to stop enrollment and study vaccinations if AEs that 
meet the halting criteria are reported. The DMID Medical Monitor and the ISM (as deemed 
necessary) will be responsible for reviewing SAEs in real time. The DSMB will review SAEs on 
a regular basis and ad hoc during this trial. 


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10 
CLINICAL MONITORING 
10.1 
Site Monitoring Plan 
Site monitoring is conducted to ensure that the human subjects’ protections, study and laboratory 
procedures, study intervention administration, and data collection processes are of high quality 
and meet sponsor, ICH/GCP guidelines and applicable regulations, and that this trial is 
conducted in accordance with the protocol, protocol-specific MOP and applicable sponsor 
standard operating procedures. DMID, the sponsoring agency, or its designee will conduct site-
monitoring visits as detailed in the clinical monitoring plan. 
Site visits will be made at standard intervals as defined by DMID and may be made more 
frequently as directed by DMID. Monitoring visits will include, but are not limited to, review of 
regulatory files, accountability records, eCRFs, informed consent forms, medical and laboratory 
reports, and protocol and GCP compliance. Site monitors will have access to each participating 
VTEU site, study personnel, and all study documentation according to the DMID-approved site 
monitoring plan. Study monitors will meet with site principal investigators to discuss any 
problems and actions to be taken and document visit findings and discussions. 


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11 
STATISTICAL CONSIDERATIONS 
11.1 
Introduction 
The goal of this clinical trial is to assess in healthy adults ages 19 – 64 and in healthy adults ages 
≥65 the safety, reactogenicity, and immunogenicity of a 2017 H7N9IIV manufactured by Sanofi 
Pasteur administered intramuscularly at different dosages (3.75 mcg, 7.5 mcg and 15 mcg of HA 
per dose) given with AS03 adjuvant manufactured by GSK approximately 21 days apart, and two 
dose levels (15 or 45 mcg) administered without adjuvant approximately 21 days apart. These 
treatment arms are included to allow evaluation of antigen dosage as well as the potential of the 
adjuvant to enhance the immune response to the 2017 H7N9 IIV. 
11.2 
Study Hypotheses 
This Phase II study is not designed to test a formal null hypothesis. Rather, it is intended to 
obtain sufficient data to obtain meaningful estimates of the immune response induced by this 
vaccine and to uncover any safety issues that occur at a sufficiently high rate that they might be 
observed in a study of this size. The sample size facilitates formal testing of selected hypotheses 
as discussed in Section 11.4.3, along with the probability of observing safety outcomes and the 
precision of immunogenicity outcomes. 
11.3 
Study Outcome Measures 
Please refer to study outcome measures in Section 3.2. 
11.4 
Sample Size Considerations 
Please refer to study design outlined in Section 4. 
11.4.1 
Study Population 
The study population for this clinical trial includes males and non-pregnant females, aged 19 
years and older, who are in good health and meet all eligibility criteria. The subjects will be 
recruited from the general population at the participating VTEU sites that have substantial 
experience conducting large influenza vaccine studies. 


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11.4.2 
Subject Enrollment and Follow-up 
Based on the accrual rates observed in similar studies, it seems reasonable to expect that the 
participating VTEUs will be able to enroll this trial in a timely fashion. In previous DMID trials 
of A/H7N9 vaccines, 5 VTEUs recruited 975 healthy adults ages 19-64 in 10 weeks, and 10 
VTEU sites (or sub-contracted sites) recruited 479 healthy adults ≥65 years old in 14 weeks. 
Prior experience suggests up to 5% of subjects ages 19 – 64, and 12% of subjects ages ≥65 may 
be excluded from the per protocol analysis for the primary immunogenicity outcome either 
because they did not receive the second study vaccination, were lost-to-follow-up, or because 
they had a protocol deviation requiring their exclusion from the per protocol analysis.  
Within the 19-64 years age stratum, over enrollment up to 5% is allowed, to ensure a minimum 
of n=100 per adjuvanted treatment arm and n = 50 per unadjuvanted treatment arm are available 
for the primary immunogenicity analysis. Within the ≥65 years treatment arm a minimum of 60 
subjects are planned to enroll in each adjuvanted treatment arm and a minimum of 30 subjects 
are planned to enroll in each unadjuvanted treatment arm to ensure at least 50 subjects in each 
adjuvanted arm and 25 subjects in each unadjuvanted arm are available for analysis of the 
primary immunogenicity endpoint. Enrollment within this age stratum may continue up to 
approximately 75 subjects per adjuvanted arm and approximately 38 subjects per unadjuvanted 
arm. 
Follow-up will consist of 2 segments. The first encompasses the core data for this trial and will 
consist of results for all study visits through approximately 21 days after the last study 
vaccination. The second segment consists of a 6-month immunogenicity assessment and follow-
up safety assessments through approximately 12 months after the last study vaccination. 
11.4.3 
Sample Size 
This study is planned to enroll a minimum of 160 subjects in each adjuvanted treatment arm (100 
in 19-64 years age stratum, 60 in ≥65 years stratum), and 80 subjects in each unadjuvanted 
treatment arm (50 in 19-64 years age stratum, 30 in ≥65 years stratum). The sample size for this 
study was selected to obtain preliminary estimates in a time critical manner. While this study is 
not designed to test any specific null hypothesis, the following tables illustrate the precision and 
power that is available for select estimates and comparisons of interest. 
 
Table 3 indicates the probability of observing one or more safety events, such as solicited 
injection site or systemic reactogenicity events or an unsolicited non-serious AE of a particular 
type for a single adjuvanted treatment arm/stratum (N = 60, or 100), for a single adjuvanted 


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treatment arm combined over age strata (N=160), for all subjects receiving unadjuvanted vaccine 
(N = 160), and for all subjects receiving adjuvanted vaccine (N = 480). 
Table 3: Power (%) to Detect Safety Events: 
Event 
Frequency 
N = 60 
N = 100 
N = 160 
N = 480 
≥10% 
Very Common 
>99 
>99 
>99 
>99 
≥1% 
Common 
45 
63 
80 
>99 
≥0.1% 
Uncommon 
6 
10 
15 
38 
≥0.01% 
Rare 
<1 
1 
2 
5 
Binomial confidence intervals (CI) are widest (have the least precision) when the response rate is 
50%. Table 4 is presented to indicate the worst case scenario for precision of observed exact 
(Clopper-Pearson) binomial confidence intervals. 
Table 4: Precision of Binomial Confidence Intervals: 
N 
95% CI 
60 
37-63 
100 
40-60 
160 
42-58 
480 
45-55 
Table 5 illustrates the minimum detectable differences in the proportion of subjects responding 
(e.g., attaining seroconversion or a titer ≥1:40) between two adjuvanted treatment arms within 
each stratum using a two-sided Likelihood Ratio Test and alpha = 0.05. 
Over enrollment is allowed as described in Section 11.4.3, to ensure a minimum of n=100 per 
adjuvanted treatment arm in the 19-64 years age stratum, therefore power calculations will 
assume n=100 per group. Based on previous DMID A/H7N9 trials it is expected 5% of enrolled 
subjects in this stratum may be excluded from analysis of the primary endpoint. In the event that 
only 100 subjects are actually enrolled in a treatment arm, the small dropout rates anticipated 
would have a minimal impact on the calculations below.  
Within the ≥65 years treatment arm a dropout rate of up to 12% is expected based on previous 
DMID trials in this population, so a minimum of 60 subjects are planned to enroll in each 
treatment arm to ensure at least 50 are available for analysis of the primary immunogenicity 
endpoint. 
 


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Table 5: Minimum Detectable Difference in Proportion Responders with 80% Power 
Assumed Proportion of subjects with titer 
≥40 in comparator arm 
19-64 years stratum  
(N = 100) 
≥65 years stratum 
(N = 50) 
0.40 
0.19 
0.27 
0.50 
0.19 
0.27 
0.60 
0.18 
0.25 
0.70 
0.16 
0.21 
0.80 
0.13 
0.16 
0.90 
0.08 
0.10 
Per FDA guidance, for differences in HAI antibody response rates, the lower confidence limit on 
the appropriate point estimate excluding equality (i.e., 0 for the difference parameter) may be 
sufficient to demonstrate the added value of the adjuvant. Table 6 and Table 7 show the lower 
bound of the 95% confidence interval for the difference in the proportion responders between the 
adjuvanted and unadjuvanted arms (e.g. 15 mcg + AS03 minus 45 mcg unadjuvanted) assuming 
the proportion of responders in the unadjuvanted arm is 0.10 and considering a range for the 
proportion of responders in the adjuvanted arm ranges from 0.50 to 0.90.  
Table 6: Lower Confidence bound2 for difference in proportion of responders  
between Adjuvanted (N = 100) and unadjuvanted (N = 50) arms, 19-64 years stratum 
Adjuvanted Arm 
Unadjuvanted 
Arm 
Difference 
Lower Confidence 
Bound 
0.50 
0.10 
0.40 
0.26 
0.60 
0.10 
0.50 
0.36 
0.70 
0.10 
0.60 
0.46 
0.80 
0.10 
0.70 
0.56 
0.90 
0.10 
0.80 
0.67 
 
Table 7: Lower Confidence bound2 for difference in proportion of responders  
between Adjuvanted (N = 50) and unadjuvanted (N = 25) arms, ≥65 years stratum 
Adjuvanted Arm 
Unadjuvanted 
Arm 
Difference 
2:1 Allocation 
NUA=25 
0.50 
0.10 
0.40 
0.19 
0.60 
0.10 
0.50 
0.29 
0.70 
0.10 
0.60 
0.39 
0.80 
0.10 
0.70 
0.49 
0.90 
0.10 
0.80 
0.60 
2. Farrington-Manning confidence limits.  


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11.5 Planned Interim Analyses 
Interim analyses will only be used to terminate this trial in the event that unanticipated safety 
events deemed to be of sufficient concern require such action by the sponsor. These assessments 
will not be made on the basis of testing a formal statistical hypothesis; therefore, p-value 
adjustment will not be made to any analyses. A DSMB will be convened by DMID to review 
study progress and participant, clinical, safety, and reactogenicity and immunogenicity data as 
described in Section 9.6.2. 
An interim analysis of immunogenicity is planned, as described in Section 11.5.2, which 
includes a series of Expedited Interim Immunogenicity Reports of serum HAI and Neut antibody 
responses. This information will be reviewed due to the extraordinary need to inform public 
health decision makers in their preparations for their response to a potential 2017 A/H7N9 
pandemic. Although interim immunogenicity results will not be used to make decisions 
concerning the conduct of this trial, they may be used to make decisions on activities external to 
this trial, e.g., designing future trials of the 2017 H7N9 IIV with and without AS03 adjuvant in 
other age groups. 
Additionally, a preliminary report of safety and immunogenicity data through Day 202, including 
a set of “topline” immunogenicity and safety tables produced on an expedited timeline, may be 
prepared as described in section 11.6; though this report will be released while subjects remain in 
the trial for long-term safety follow-up, it will be considered the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. If 
this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 
11.5.1 
Interim Safety Review 
An interim safety review may include enrollment and demographic information, medical history, 
concomitant medications, physical assessments, clinical laboratory values, dosing compliance, 
and solicited and unsolicited AE/SAEs. Additional data may be requested by the DSMB, and 
interim statistical reports may be generated as deemed necessary and appropriate by DMID. The 
DSMB may receive data in aggregate and presented by treatment arm. The DSMB may also be 
provided with expected and observed rates of the expected AEs in an unblinded fashion, and may 
request the treatment assignment be unblinded for an individual subject if required for safety 
assessment. The DSMB will review grouped and unblinded data in the closed session only. The 
DSMB will meet and review this data at scheduled time points or ad hoc as needed during this 
trial as defined in the DSMB charter. As an outcome of each review/meeting, the DSMB will 


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make a recommendation as to the advisability of proceeding with study vaccinations (as 
applicable), and to continue, modify, or terminate this trial. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Section 9.5 are met. 
11.5.2 
Interim Immunogenicity Review 
There is no plan to halt this trial prior to full enrollment and completion of all follow-up visits 
based on interim immunogenicity results.  
A series of Expedited Interim Immunogenicity Reports of HAI and Neut serum antibody 
responses comparing venous blood samples collected at baseline (D1), Visit 03 (D8), Visit 06 
(D29), and Visit 07 (D43) is planned. Reports will include HAI and Neut results for 
approximately 25 subjects per adjuvanted treatment arm and 13 subjects per unadjuvanted 
treatment arm within the 19-64year-old stratum and the first 15 subjects per adjuvanted treatment 
arm and 8 subjects per unadjuvanted treatment arm within the ≥65 year-old stratum. Reports will 
be prepared following each post-vaccination visit. This information will be reviewed due to the 
extraordinary need to inform public health decision makers in their preparations for their 
response to a potential 2017 A/H7N9 pandemic. These data will be archived by the SDCC, but 
will not be part of the final clinical database for this study, nor will they be made available to the 
clinical investigators for publication. 
Immune responses will be summarized in terms of strain-specific 2017 A/H7N9 HAI and Neut 
antibody titers and the relationship to study vaccine dosage and adjuvant use. It is anticipated 
that all analyses will be carried out in parallel for both assays, but reports may be prepared 
separately for HAI and Neuts if results are available on different timelines. Interim analyses will 
focus on rates of titers ≥1:40, seroconversion (defined as either a pre-vaccination titer <1:10 and 
a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a minimum four-fold rise in 
post-vaccination titer) and Geometric Mean Titers (GMTs), along with corresponding 95% 
confidence intervals. No formal hypothesis testing will be included in the interim analysis. 
Immunogenicity reports will be provided by the SDCC to the DMID Scientific Lead and Clinical 
Project manager, and the DSMB. Reports will include data summarized by unblinded treatment 
arm, but the presentation will be in a format that prevents inadvertent unblinding of any 
individual subject. 


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11.6 Final Analysis Plan 
Clinical, safety, and reactogenicity data through approximately 180 days after the second study 
vaccination will represent the primary clinical database for this trial. Once the last subject 
completes the visit that occurs approximately 180 days after the last study vaccination, the 
primary clinical database may be cleaned, monitored, and locked, and all serum samples will be 
sent for vaccine-strain HAI and Neut antibody assays. Unblinded analyses of safety 
reactogenicity, and primary and secondary immunogenicity data are planned. A preliminary 
report may be prepared by the SDCC after the primary clinical database is locked and all HAI 
and Neut data through 180 days after the last study vaccination are received.  
Regardless of whether a preliminary report is prepared, a “topline” subset of the immunogenicity 
and safety tables will be provided to DMID on an expedited timeline following database lock, 
concurrently with preliminary report or CSR generation. These analyses may be made available 
to the sponsor for planning subsequent trials and to the lead principal investigator for 
publication. These analyses will not be used to make any decisions concerning the conduct of 
this trial. As it is anticipated that subjects may remain in long term safety follow-up at the time 
of these analyses, blinded investigators and DMID medical monitors not involved in the analysis, 
publication, or clinical study report preparation will be responsible for assessing SAEs and 
MAAEs including PIMMCs and new onset chronic medical conditions until all subjects have 
completed the final follow-up visit. All analyses of data included in the topline and preliminary 
report for early release will be considered the final analysis of these data, and also included in the 
final clinical study report (CSR). 
Analysis of exploratory immunogenicity endpoints may be performed and released as the data 
are available from the research laboratory. Any such analyses would be considered the final 
analysis for the endpoint, and included in the CSR. The final CSR will be completed after the 
last subject’s last visit is completed, and the final clinical database including all long term safety 
follow-up data is cleaned, monitored and locked. Additional exploratory immunogenicity 
endpoint data not available at the time of CSR preparation may be included in an addendum to 
the CSR. 
A formal statistical analysis plan will be developed and finalized prior to unblinding for any 
interim analysis, which defines the analyses to be included in the Expedited Interim 
Immunogenicity Reports, Preliminary report, and the final CSR. 
11.6.1 
Analysis Populations 
The Safety Analysis population includes all subjects who received at least one dose of study 
vaccine. 


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The modified intent-to-treat (mITT) population includes all subjects who received at least one 
dose of study vaccine and contributed both pre- and at least one post-study vaccination venous 
blood samples for immunogenicity testing (HAI or Neut antibody assays) for which valid results 
were reported. For analyses using the mITT population, subjects will be grouped based on 
randomized treatment arm.  
The per protocol (PP) population includes all subjects in the mITT subset with the following 
exclusions: 
• Data from all available visits for subjects found to be ineligible at baseline. 
• Data from all visits subsequent to major protocol deviations, such as: 
• Second study vaccination not received, 
• Second study vaccination received out of window, 
• Receipt of non-study licensed live vaccine within 30 days before or after each study 
vaccination, 
• Receipt of non-study licensed inactivated vaccine within 14 days before or after 
each study vaccination, 
• Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before 
or after each study vaccination. 
• Data from any visit that occurs substantially out of window. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received. 
11.6.2 
Safety Data 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. All 
summaries and analyses will be presented for all subjects, and by age stratum. 
Solicited AEs will be summarized by severity for each day after each study vaccination (Days 1-
7 post each study vaccination) and as the maximum severity over all 8 days. Additionally, 
solicited AEs will be analyzed by taking the most severe response over the follow-up period, 
dichotomizing into a binary variable (none versus mild, moderate, or severe) and using standard 
techniques, such as exact confidence intervals, to summarize the proportion of subjects reporting 
each symptom, any injection site symptom, and any systemic symptom. Summaries of solicited 
AEs will be presented separately for each study vaccination as well as overall study vaccinations 
by treatment arm. The proportion of subjects reporting symptoms may be compared between 


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treatment arms using Chi-square or Fisher’s exact test. The proportion of subjects reporting 
solicited symptoms between the different study vaccinations (i.e., first and second) will be 
compared using McNemar’s test. 
Unsolicited AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) for 
preferred term and system organ class (SOC). The numbers of SAEs, MAAEs, including 
NOCMCs, and PIMMCs are likely to be small in this trial and will be reported by detailed 
listings showing the event description, MedDRA preferred term and SOC, relevant dates (study 
vaccinations and AEs), severity, relatedness, and outcome for each event. Non-serious 
unsolicited AEs will be summarized as number and percentage of subjects reporting at least one 
event in each MedDRA preferred term and SOC, cross tabulated by severity and relationship to 
study product. Additionally, the proportion of subjects and exact 95% confidence intervals of 
AEs in aggregate and by MedDRA categories will be computed. 
Clinical laboratory data will be summarized by severity for each visit and as the maximum over 
all post-study vaccination visits. Graphical presentations may include box plots. 
11.6.3 
Immunogenicity Data  
Summaries and analysis of immunogenicity data will be presented for the mITT and PP 
populations. 
Immune responses in terms of strain-specific 2017 H7N9 HAI and Neut antibody titers will be 
summarized by treatment arm at each time point. Analyses will include percentage of subjects 
with a titer ≥1:40, percentage of subjects achieving seroconversion (defined as either a pre-
vaccination titer <10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a 
minimum four-fold rise in post-vaccination antibody titer), and GMTs along with corresponding 
95% confidence intervals. Descriptive summary statistics will be provided for all assays and time 
points. The correlation between HAI and Neut antibody titers will be evaluated. Plots such as 
reverse cumulative distributions or longitudinal presentations of GMTs will be presented. 
Additionally, the immune response, as described above, will be summarized by available 
covariates, such as age, sex, body mass index, and prior receipt of seasonal influenza vaccine(s), 
and these covariates may be considered statistical modeling. As an exploratory analysis, models 
will be developed to evaluate the relationship between dosage and adjuvant on immune response. 
For example, logistic regression may be used to examine the relationship of proportion of 
responders with dosage and adjuvant, and available covariates may be considered for inclusion in 
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Additionally, N9 NA specific antibody assays are in development.  If successful, N9 NA specific 
responses may be assessed at baseline, and 8, 29, 43 and 202 after receipt of the first study 
vaccination.  For each time point summaries will include percentage of subjects with detectable 
N9 NA response (to be defined in SAP based following assay development and selection) and 
GMTs along with corresponding 95% confidence intervals. Descriptive summary statistics will 
be provided for all assays and time points. The correlation of N9 NA response with HAI and 
Neut antibody titers will be evaluated, and plots such as reverse cumulative distributions or 
longitudinal presentations of GMTs will be presented. 
Further, a determination of the NA content of the 2017 H7N9 IIV is planned, and if successful 
may be used to correlate the N9 NA elicited antibody responses to the NA content of the 2017 
H7N9 IIV. Detectable NA antibody responses and GMTs will be summarized stratified by NA 
content, and statistical modeling may be used to examine the relationship of NA response with 
NA vaccine content, HA antigen dosage, and adjuvant.  
At least a subset of samples will also be tested for cross-reactive serum HAI and Neut antibody 
responses to antigenically drifted variants of influenza A/H7 viruses. Strain-specific results will 
be summarized using descriptive statistics as described above, correlations with 2017 H7N9 
responses, and association with study vaccine dose and adjuvant. 
Further immunogenicity testing and/or analyses may be carried out in the future based upon 
subjects’ prior receipt of non-seasonal influenza vaccines, including type (inactivated or live 
attenuated), what subtype (e.g. A/H3, A/H5, A/H9) and approximate date of vaccination. 
11.6.4 
Missing Values and Outliers 
All attempts will be made to collect all data per protocol. As missing data are expected to be 
minimal, no imputation will be performed for missing values. Any data point that appears to be 
erroneous or inexplicable based on clinical judgment will be investigated as a possible outlier. If 
data points are identified as outliers, sensitivity analyses will be performed to examine the 
impact of including or excluding the outliers. Any substantive differences in these analyses will 
be reported. 


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12 
DATA COLLECTION FORMS AND ACCESS TO 
SOURCE DATA/DOCUMENTS 
Each participating VTEU site will maintain appropriate medical and research records for this 
trial, in compliance with ICH E6, Section 4.9, and regulatory and institutional requirements for 
the protection of confidentiality of subjects. Each participating VTEU site will permit authorized 
representatives of the DMID, its designees, and appropriate regulatory agencies to examine (and 
when required by applicable law, to copy) clinical trial records for the purposes of quality 
assurance reviews, audits, monitoring and evaluation of the study safety and progress. These 
representatives will be permitted access to all source data, which include, but are not limited to, 
hospital records, clinical and office charts, laboratory notes, memoranda, evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions 
certified after verification as being accurate and complete, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, and subject files and records kept at the pharmacy, at the 
laboratories, and medico-technical departments involved in the trial. Source data are all 
information, original records of clinical findings, observations, or other activities in a clinical 
trial necessary for the reconstruction and evaluation of the trial. 
Interview of subjects is sufficient for obtaining medical history. Solicitation of medical records 
from the subject’s primary care provider is not required. 


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13 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted site quality management plan, each participating VTEU site 
is responsible for conducting routine quality assurance (QA) and quality control (QC) activities 
to internally monitor study progress and protocol compliance. Each participating site principal 
investigator will provide direct access to all study-related sites, source data/data collection forms, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. Each site principal investigator will ensure all study personnel are 
appropriately trained and training documentation is current and maintained on site. 
The SDCC will implement QC procedures beginning with the data entry system and generate 
data QC checks that will be run on the database. Any missing data or data anomalies will be 
communicated to the participating VTEU site(s) for clarification and resolution. 


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14 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1 
Ethical Standard 
The site principal investigator will ensure that this trial is conducted in full conformity with 
principles of the Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR 46, 21 CFR 50 
and 56, and ICH E6; 62 Federal Regulations 25691 (1997), if applicable. The site principal 
investigator’s institution will hold a current Federalwide Assurance (FWA) issued by the Office 
of Human Research Protection (OHRP) for federally funded research. 
14.2 
Institutional Review Board 
Prior to enrollment of subjects into this trial, the protocol and informed consent form will be 
reviewed and approved by the appropriate IRB listed on its FWA. 
The responsible official for the IRB will sign the IRB letter of approval of the protocol prior to 
the start of this trial and a copy will be provided to DMID. The IRB FWA number will be 
provided to DMID. 
Should amendments to the protocol be required, the amendments will be written by the sponsor 
and provided to the site principal investigator for submission to the IRB. 
14.3 
Informed Consent Process 
14.3.1 
Informed Consent 
The site principal investigator will choose subjects in accordance with the eligibility criteria 
detailed in Section 5.1. Before any study procedures are performed, subjects must sign an ICF 
that complies with the requirements of 21 CFR Part 50 and 45 CFR 46 and the local IRB. Study 
personnel may employ IRB-approved recruitment efforts prior to obtaining study consent; 
however, before any study procedures are performed to determine protocol eligibility an ICF 
must be signed.  
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Before any study procedures 
are performed subjects will receive a comprehensive explanation of the proposed study 


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procedures and study interventions/products. This will include the nature, risks and possible 
benefits of this trial, alternate therapies, any known AEs, the investigational status of the study 
interventions/products, and the other elements that are part of obtaining proper informed consent. 
Subjects will also receive a detailed explanation of the proposed use and disclosure of their 
protected health information, including specifically their serum samples. Subjects will be 
allowed sufficient time to consider participation in this research trial, after having the nature, 
risks, and possible benefits of this trial explained to them, and have the opportunity to discuss 
this trial with their family, friends, or legally authorized representative, or think about it prior to 
agreeing to participate. 
ICFs describing in detail the study interventions/products, study procedures, risks, and possible 
benefits will be given to subjects. The ICF must not include any exculpatory statements. ICFs 
will be IRB-approved and subjects will be asked to read and review the appropriate document. 
Upon reviewing the appropriate document, the site principal investigator (or designee) will 
explain this research trial to subjects and answer any questions that may arise. Subjects must sign 
the ICF, and written documentation of the informed consent process is required prior to starting 
any study procedures being done specifically for this trial, including determining eligibility and 
administering study product. 
By signing the ICF, subjects agree to complete all study procedures required by this trial, unless 
the subject withdraws voluntarily, or is withdrawn or terminated from this trial for any reason. 
The rights and welfare of subjects will be protected by emphasizing to subjects that the quality of 
their medical care will not be adversely affected if they decline to participate in or withdraw 
from this trial. 
DMID will provide the site principal investigator, in writing, any new information that 
significantly impacts the subject’s risk of receiving the investigational products. This new 
information will be communicated by the site principal investigator to subjects who consent to 
participate in this trial in accordance with IRB requirements. The ICF will be updated and 
subjects will be re-consented per IRB requirements, if necessary. Subjects will be given a copy 
of all ICFs that they sign. 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
This trial will be inclusive of all subjects age 19 and above who meet the Subject Inclusion 
Criteria (see Section 5.1.1) and do not meet the Subject Exclusion Criteria (see Section 5.1.2), 
regardless of religion, sex, or ethnic background. Adults aged 18 are excluded because the CDC-
recommended adult immunization schedule considers adults as age 19 and above, and therefore 
this is the subject population chosen for this study [69]. Should the outcome of this trial be 
deemed acceptable, additional trials may be initiated including those in other populations. 


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It is unknown if the 2017 H7N9 IIV with or without AS03 adjuvant poses any risks to an unborn 
child. As of November 22, 2015 (per the most current version of the manufacturer’s IB), the 
available data for women who become pregnant during clinical trials of AS03-adjuvanted (pre) 
pandemic influenza vaccines do not suggest any causal relationship between adverse pregnancy 
outcomes and receipt of an AS03-adjuvanted vaccine. Women of childbearing potential who are 
not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or 
successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with 
documented radiological confirmation test at least 90 days after the procedure, and still 
menstruating or <1 year of the last menses if menopausal must agree to practice highly effective 
contraception that may include, but not limited to, non-male sexual relationships, abstinence 
from sexual intercourse with a male partner, monogamous relationship with a vasectomized 
partner who has been vasectomized for 180 days or more prior to the subject receiving the first 
study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam,, 
effective intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, 
injectables, or oral contraceptives (“the pill”), with use of a highly effective method of 
contraception for a minimum of 30 days prior to study product exposure and agree to practice 
highly effective contraception for the duration of study product exposure, including 60 days after 
their last study vaccination. A highly effective method of contraception is defined as one that 
results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. In 
addition to contraceptive use, all women of childbearing potential will be required to have a 
negative urine or serum pregnancy test within 24 hours prior to each study vaccination. If a 
female subject becomes pregnant while participating in this trial, we will ask her permission to 
follow-up with her about her health and the health of her baby through pregnancy outcome. 
Children will not be included in this trial as presently there are no safety or efficacy data in 
adults. 
14.5 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the site principal investigators, other study 
personnel, the sponsor, and their agents. The confidentiality includes documentation, 
investigation data, subject’s clinical information and all other information generated during 
participation in the study. No information concerning the study or the data generated from the 
study will be released to any unauthorized third parted without prior written approval of the 
DMID and the subject.  Subject confidentiality will be maintained when study results are 
published or discussed in conferences. The study monitor or other authorized representatives of 
the sponsor or government regulatory agencies may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records (office, clinic, 


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or hospital) and pharmacy records for the subjects in this study. The clinical study site will 
permit access to such records.  
To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings.  The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the Federal 
Food and Drug Administration (FDA). 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing 
information about themselves or their involvement in this research.  If any person or agency 
obtains a written consent to receive research information, then the researchers may not use the 
Certificate to withhold that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
subject’s consent, information that would identify the subject as a participant in the research 
project regarding matters that must be legally reported including: child and elder abuse, sexual 
abuse, or wanting to harm themselves or others.   
 
   
14.6 
Study Discontinuation 
If this trial is discontinued, subjects, who have signed the informed consent form and are 
randomized and vaccinated, will continue to be followed for safety for the duration of the 
prescribed safety follow-up period. No further study vaccinations will be administered. 
14.7 
Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for taking part in this trial. 
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with the local IRB’s policies and procedures, and subject to IRB approval. 
If it is determined by the participating VTEU site and the site principal investigator that an injury 
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referrals to appropriate health care facilities will be provided to the subject. Study personnel will 
try to reduce, control, and treat any complications from this trial. Immediate medical treatment 
may be provided by the participating VTEU site, such as giving emergency medications to stop 
immediate allergic reactions to the study vaccine. No financial compensation will be provided to 
the subject by the participating VTEU site for any injury suffered due to participation in this 
trial. 
For this protocol, the study products (monovalent inactivated influenza 2017 H7N9 virus vaccine 
manufactured by Sanofi Pasteur and adjuvant (AS03) manufactured by GSK), are covered under 
the Public Readiness and Emergency Preparedness Act (PREP Act), as described in Section 
2.1.1. 
14.8 
Future Use of Stored Specimens 
Residual samples/specimens are those that are left over after the study has been completed. 
Subjects may be asked for permission to keep any remaining (residual) clinical samples (serum) 
derived from venous blood samples for possible use in future research studies, such as examining 
additional immunological assessments or testing for antibodies against other viruses or bacteria, 
or the retention of those samples for possible future use may be a condition of study 
participation. Residual clinical samples for future use will be stored indefinitely at a central 
clinical storage facility and may be shared for purposes other than per protocol analysis with 
investigators at the participating VTEU site and with other investigators at other institutions once 
the clinical study report has been finalized. 
Other blood samples are being collected during the study specifically for future use, from 
subjects who consent to collection of those specimens either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or by 
indicating that they opt in to sample collection for future use if the informed consent form allows 
the option to choose that option. It is anticipated that up to ten 0.5 mL aliquots of serum from 
each extra 10 mL venous blood sample will be available specifically for the purpose of future 
research, including but not limited to non-traditional immune assay development, assessing 
innate immune factors, and the ability of H7 vaccine-induced antibodies to cross-react with other 
influenza viruses. These future research clinical samples will be stored indefinitely at a central 
clinical storage facility. 
Unlike residual samples, samples/specimens collected during the study solely for the purpose of 
future research may be requested from DMID and shipped from the DMID CAR at any time. 
The samples (residual and the extra venous blood sample collected solely for future use) will not 
be sold or used directly for production of any commercial product. No genetic tests will be 
performed on samples. Each sample will be encoded (labeled) only with a barcode and a unique 
tracking number to protect subject confidentiality. 


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There are no benefits to subjects in the collection, storage and subsequent use of their specimens 
for future research. Reports about future research done with subjects’ samples will NOT be kept 
in their health records. 
Subjects who are provided the option to decide if residual samples may be retained for possible 
future use or if other blood specimens may be collected specifically for future use may change 
those decisions at any time by notifying the study doctors or nurses in writing. However, if the 
subject originally consents to future use of residual samples or collection of samples specifically 
for future use, and subsequently changes his/her decision, any data from a previously collected 
sample may still be used for this research. 


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15 
DATA HANDLING AND RECORD KEEPING 
The site principal investigator is responsible to ensure the accuracy, completeness, legibility, and 
timeliness of the data reported. 
Data collection forms will be derived from the eCRF and provided by the SDCC to record and 
maintain data for each subject enrolled in this trial. All data collection forms should be 
completed in a neat, legible manner to ensure accurate interpretation of data. Black or blue ink is 
required to ensure clarity of reproduced copies. When making a change or correction, cross out 
the original entry with a single line and initial and date the change. Do not erase, overwrite, or 
use correction fluid or tape on the original. 
Data reported in the eCRF derived from the data collection forms should be consistent with the 
data collection forms or the discrepancies should be explained. 
The sponsor and/or its designee will provide guidance to the site principal investigators and other 
study personnel on making corrections to the data collection forms and eCRF. 
15.1 
Data Management Responsibilities 
All data collection forms and laboratory reports must be reviewed by the clinical team and data 
entry personnel, who will ensure that they are accurate and complete. AEs must be recorded on 
the appropriate data collection form, assessed for severity and relationship, and reviewed by the 
site principal investigator or appropriate sub-investigator. 
Data collection is the responsibility of the study personnel at each participating VTEU site under 
the supervision of the respective site principal investigator. During this trial, the site principal 
investigator must maintain complete and accurate documentation for this trial. 
The SDCC for this trial will be responsible for data management, quality review, analysis, and 
reporting of the study data. 
15.2 
Data Capture Methods 
Clinical (including, but not limited to, AE/SAEs, concomitant medications, medical history, 
physical assessments, and clinical laboratory values), reactogenicity and immunogenicity data 
will be entered into a 21 CFR 11-compliant Internet Data Entry System provided by the SDCC. 
The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical and 
reactogenicity data will be entered directly from the data collection forms completed by the study 
personnel. 


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15.3 
Types of Data 
Data for this trial will include clinical, safety, and outcome measures (e.g., clinical laboratory 
values, reactogenicity and immunogenicity data). 
15.4 
Timing/Reports 
A series of Expedited Interim Immunogenicity Reports of HAI and Neut serum antibody 
responses comparing venous blood samples collected at baseline (D1), Visit 03 (D8), Visit 04 
(D22), Visit 06 (D29), and Visit 07 (D43) is planned. Reports will include HAI and Neut results 
for approximately 25 subjects per adjuvanted treatment arm and 13 subjects per unadjuvanted 
treatment arm within the 19-64year-old stratum and the first 15 subjects per adjuvanted treatment 
arm and 8 subjects per unadjuvanted treatment arm within the ≥65 year-old stratum. Reports will 
be prepared following each post-vaccination visit. 
Clinical, safety and reactogenicity data through approximately 180 days after the second study 
vaccination will represent the primary clinical database for this trial. Once the last subject 
completes the visit that occurs approximately 180 days after the last study vaccination, the 
primary clinical database may be cleaned, monitored and locked. Unblinded analyses of safety, 
reactogenicity, and primary and secondary immunogenicity data is planned. A preliminary report 
may be prepared by the SDCC after the primary clinical database is locked and all HAI and Neut 
data through 180 days after the last study vaccination are received.  
Regardless of whether a preliminary report is prepared, a “topline” subset of the immunogenicity 
and safety tables will be provided to DMID on an expedited timeline following database lock, 
concurrently with preliminary report or CSR generation. These analyses may be made available 
to the sponsor for planning subsequent trials and to the lead principal investigator for 
publication. These analyses will not be used to make any decisions concerning the conduct of 
this trial. As it is anticipated that subjects may remain in safety follow-up for 12 months after last 
study vaccination at the time of these analyses, each site will have at least one investigator 
blinded to perform safety assessments. In addition, blinded investigators and medical monitors 
not involved in the analysis, publication, or clinical study report preparation will be responsible 
for assessing SAEs and MAAEs including PIMMCs and new onset chronic medical conditions 
until all subjects have completed the final follow-up visit. All analyses of data included in the 
topline and preliminary report for early release will be considered the final analysis of these data, 
and also included in the final clinical study report (CSR). 
Analysis of exploratory immunogenicity endpoints may be performed and released as the data is 
available from the central clinical laboratory. Any such analyses would be considered the final 
analysis for the endpoint, and included in the CSR. 


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The final CSR will be completed after the last subject’s last visit is completed, and the final 
clinical database including all long-term safety follow-up data is cleaned, monitored and locked. 
Additional exploratory immunogenicity endpoint data not available at the time of CSR 
preparation may be included in an addendum to the CSR. 
Additional statistical reports may be generated as deemed necessary and appropriate by DMID. 
Safety and immunogenicity summary reports may be generated for the DSMB. 
After the final CSR is complete, and upon request and DMID approval, the SDCC will provide 
the participating VTEU sites with a summary of results by treatment arm and/or subject 
treatment assignments. In this regard, the participating VTEU sites requesting such information 
to share with study subjects must do so in compliance with their respective IRB guidelines. 
15.5 
Study Records Retention 
Study records and reports including, but not limited to, eCRFs, source documents, ICFs, and 
study drug disposition records shall be maintained for 2 years after a marketing application is 
approved for the drug for the indication for which it is being investigated; or, if no application is 
to be filed or if the application is not approved for the drug, until 2 years after the investigation is 
discontinued and the FDA has been notified. Informed consent forms for future use will be 
maintained as long as the sample exists. 
The participating VTEU sites must contact DMID for authorization prior to the destruction of 
any study records.  


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16 
PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the study protocol, GCP, or protocol-specific 
MOP requirements. The noncompliance may be either on the part of the subject, the site 
principal investigator, or other study personnel. As a result of deviations, corrective actions are 
to be developed by the site and implemented promptly. 
These practices are consistent with ICH E6: 
4.5 
Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance and Quality Control, Section 5.1.1 
5.20 
Noncompliance, Sections 5.20.1, and 5.20.2 
It is the responsibility of the site principal investigator and other study personnel to use 
continuous vigilance to identify and report deviations within five working days of identification 
of the protocol deviation, or within five working days of the scheduled protocol-required 
activity. All deviations must be promptly reported to DMID, via the SDCC’s AdvantageEDCSM. 
All protocol deviations, as defined above, must be addressed in study subject data collection 
forms. A completed copy of the DMID Protocol Deviation Form must be maintained in the 
Regulatory File as well as in the subject's chart. Protocol deviations must be sent to the local IRB 
per its guidelines. The site principal investigator and other study personnel are responsible for 
knowing and adhering to their IRB requirements. 


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17 
PUBLICATION POLICY 
All investigators funded by the NIH must submit or have submitted for them to the National 
Library of Medicine’s PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) an electronic 
version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made 
publicly available no later than 12 months after the official date of publication. The NIH Public 
Access Policy ensures the public has access to the published results of NIH funded research. It 
requires investigators to submit final peer-reviewed journal manuscripts that arise from NIH 
funds to the digital archive PubMed Central upon acceptance for publication. Further, the policy 
stipulates that these papers must be accessible to the public on PubMed Central no later than 12 
months after publication. 
Refer to: 
• 
NIH Public Access Policy, http://publicaccess.nih.gov/ 
• 
NIH Office of Extramural Research (OER) Grants and Funding, 
http://grants.nih.gov/grants/oer.htm 
As of January 2018, all clinical trials supported by the NIH must be registered on 
ClinicalTrials.gov, no later than 21 days after the enrollment of the first subject. Results of all 
clinical trials supported by the NIH, generally, need to be submitted no later than 12 months 
following the primary completion date. A delay of up to 2 years is available for trials that meet 
certain criteria and have applied for certification of delayed posting. 
As part of the result posting a copy of this protocol (and its amendments) and a copy of the 
Statistical Analysis Plan will be posted on ClincialTrials.gov. 
For this trial the responsible party is DMID which will register the trial and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to: 
• 
Public Law 110-85, Section 801, Clinical Trial Databases 
• 
42CFR11 
• 
NIH NOT-OD-16-149 


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18 
LITERATURE REFERENCES 
 
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Fouchier, R.A., et al., Avian influenza A virus (H7N7) associated with human 
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Matzkin, H. and E. Nili, Accidental tenfold overdose of influenza vaccine: a clinical and 
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Mostow, S.R., et al., Inactivated vaccines. 1. Volunteer studies with very high doses of 
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Palache, A.M., et al., Antibody response after influenza immunization with various 
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Remarque, E.J., et al., Improvement of the immunoglobulin subclass response to 
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Ruben, F.L. and G.G. Jackson, A new subunit influenza vaccine: acceptability compared 
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Ruben, F.L., C.W. Potter, and C.H. Stuart-Harris, Humoral and secretory antibody 
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Keitel, W.A., et al., Increasing doses of purified influenza virus hemagglutinin and 
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24. 
Couch, R.B., et al., A randomized clinical trial of an inactivated avian influenza A 
(H7N7) vaccine. PLoS One, 2012. 7(12): p. e49704. 
25. 
Treanor, J.J., et al., Safety and immunogenicity of an inactivated subvirion influenza A 
(H5N1) vaccine. N Engl J Med, 2006. 354(13): p. 1343-51. 
26. 
Atmar, R.L. and W.A. Keitel, Adjuvants for pandemic influenza vaccines. Curr Top 
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27. 
Bresson, J.L., et al., Safety and immunogenicity of an inactivated split-virion influenza 
A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet, 2006. 
367(9523): p. 1657-64. 
28. 
Keitel, W.A., et al., Safety and immunogenicity of an inactivated influenza A/H5N1 
vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-
II randomized clinical trial. J Infect Dis, 2008. 198(9): p. 1309-16. 
29. 
Carmona, A., et al., Immunogenicity and safety of AS03-adjuvanted 2009 influenza A 
H1N1 vaccine in children 6-35 months. Vaccine, 2010. 28(36): p. 5837-44. 
30. 
Diez-Domingo, J., 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(6): p. e35-46. 
31. 
Leroux-Roels, I., et al., Antigen sparing and cross-reactive immunity with an adjuvanted 
rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet, 
2007. 370(9587): p. 580-9. 
32. 
McElhaney, J.E., et al., AS03-adjuvanted versus non-adjuvanted inactivated trivalent 
influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised 
trial. Lancet Infect Dis, 2013. 13(6): p. 485-96. 
33. 
Vogel, F.R., et al., Emulsion-based adjuvants for influenza vaccines. Expert Rev 
Vaccines, 2009. 8(4): p. 483-92. 


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34. 
Increased risk of narcolepsy observed also among adults vaccinated with Pandemrix in 
Finland 
National Narcolepsy Task Force.  National Institute for Health and Welfare (THL) Finland. 
35. 
A registry based comparative cohort study in four Swedish counties of the risk for 
narcolepsy after vaccination with Pandemrix – a first and preliminary report. 
36. 
Choe, Y.J., G.R. Bae, and D.H. Lee, No association between influenza A(H1N1)pdm09 
vaccination and narcolepsy in South Korea: an ecological study. Vaccine, 2012. 30(52): 
p. 7439-42. 
37. 
Dauvilliers, Y., et al., Increased risk of narcolepsy in children and adults after pandemic 
H1N1 vaccination in France. Brain, 2013. 136(Pt 8): p. 2486-96. 
38. 
Eurosurveillance editorial, t., Swedish Medical Products Agency publishes report from a 
case inventory study on Pandemrix vaccination and development of narcolepsy with 
cataplexy. Euro Surveill, 2011. 16(26). 
39. 
Miller, E., et al., Risk of narcolepsy in children and young people receiving AS03 
adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ, 
2013. 346: p. f794. 
40. 
Montplaisir, J., et al., Risk of narcolepsy associated with inactivated adjuvanted (AS03) 
A/H1N1 (2009) pandemic influenza vaccine in Quebec. PLoS One, 2014. 9(9): p. 
e108489. 
41. 
Nohynek, H., et al., AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase 
in the incidence of childhood narcolepsy in Finland. PLoS One, 2012. 7(3): p. e33536. 
42. 
O'Flanagan, D., et al., Investigation of an association between onset of narcolepsy and 
vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010. Euro 
Surveill, 2014. 19(17): p. 15-25. 
43. 
Wijnans, L., et al., The incidence of narcolepsy in Europe: before, during, and after the 
influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine, 2013. 31(8): p. 
1246-54. 
44. 
 A Phase II Randomized, Partially-Blinded, Controlled, Trial in Healthy Adults Aged 65 
Years and Older to Assess the Safety, Reactogenicity, and Immunogenicity of an MF59-
Adjuvanted, Monovalent Inactivated Influenza A/H7N9 Virus Vaccine Administered 
Intramuscularly at Different Intervals and Dosages. 
45. 
Chen, W.H., et al., Safety, Reactogenicity, and Immunogenicity of Inactivated 
Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 
Adjuvant. Open Forum Infect Dis, 2014. 1(3): p. ofu091. 
46. 
Jackson, L.A., et al., Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine 
With and Without AS03 and MF59 Adjuvants on Immune Response: A Randomized 
Clinical Trial. JAMA, 2015. 314(3): p. 237-46. 
47. 
Jackson, L.A., et al., Immunogenicity and safety of varying dosages of a monovalent 2009 
H1N1 influenza vaccine given with and without AS03 adjuvant system in healthy adults 
and older persons. J Infect Dis, 2012. 206(6): p. 811-20. 
48. 
Mulligan, M.J., et al., Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 
Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A 
Phase 1 Clinical Trial. Open Forum Infect Dis, 2014. 1(3): p. ofu102. 


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49. 
Mulligan, M.J., et al., Serological responses to an avian influenza A/H7N9 vaccine mixed 
at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA, 2014. 
312(14): p. 1409-19. 
50. 
Lee, Y.J., et al., Novel reassortant influenza A(H5N8) viruses, South Korea, 2014. Emerg 
Infect Dis, 2014. 20(6): p. 1087-9. 
51. 
Wu, H., et al., Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern 
China. Emerg Infect Dis, 2014. 20(8): p. 1315-8. 
52. 
Gao, R., et al., Human infection with a novel avian-origin influenza A (H7N9) virus. N 
Engl J Med, 2013. 368(20): p. 1888-97. 
53. 
Analysis of recent scientific information on avian influenza A(H7N9) virus. WHO  
Influenza Update, 2017. 
54. 
Human infection with avian influenza A(H7N9) virus – China: 07 December 2017. WHO  
Emergencies preparedness, response, 2017. 
55. 
WHO Emergencies preparedness, response- Disease Outbreak News 5 April 2017. 
56. 
Zhou, J., et al., Biological features of novel avian influenza A (H7N9) virus. Nature, 
2013. 499(7459): p. 500-3. 
57. 
Zhu, H., et al., Infectivity, transmission, and pathology of human-isolated H7N9 influenza 
virus in ferrets and pigs. Science, 2013. 341(6142): p. 183-6. 
58. 
Li, Y., et al., Evolving HA and PB2 genes of influenza A (H7N9) viruses in the fifth wave 
- Increasing threat to both birds and humans? J Infect, 2017. 
59. 
Madan, A., et al., Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic 
Influenza Vaccine in a Randomized Trial in Healthy Adults. J Infect Dis, 2016. 214(11): 
p. 1717-1727. 
60. 
Lasky, T., et al., The Guillain-Barre syndrome and the 1992-1993 and 1993-1994 
influenza vaccines. N Engl J Med, 1998. 339(25): p. 1797-802. 
61. 
Haber, P., et al., Guillain-Barre syndrome following influenza vaccination. JAMA, 2004. 
292(20): p. 2478-81. 
62. 
De Wals, P., et al., Risk of Guillain-Barre syndrome following H1N1 influenza 
vaccination in Quebec. JAMA, 2012. 308(2): p. 175-81. 
63. 
Juurlink, D.N., et al., Guillain-Barre syndrome after influenza vaccination in adults: a 
population-based study. Arch Intern Med, 2006. 166(20): p. 2217-21. 
64. 
Salmon, D.A., et al., Association between Guillain-Barre syndrome and influenza A 
(H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis. Lancet, 
2013. 381(9876): p. 1461-8. 
65. 
Wise, M.E., et al., Guillain-Barre syndrome during the 2009-2010 H1N1 influenza 
vaccination campaign: population-based surveillance among 45 million Americans. Am 
J Epidemiol, 2012. 175(11): p. 1110-9. 
66. 
Polakowski, L.L., et al., Chart-confirmed guillain-barre syndrome after 2009 H1N1 
influenza vaccination among the Medicare population, 2009-2010. Am J Epidemiol, 
2013. 178(6): p. 962-73. 
67. 
Dodd, C.N., et al., International collaboration to assess the risk of Guillain Barre 
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31(40): p. 4448-58. 
68. 
Sullivan, S.S., Narcolepsy in adolescents. Adolesc Med State Art Rev, 2010. 21(3): p. 
542-55, x-xi. 


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69. 
CDC, Recommended Immunizations for Adults: By Age. 2017. 
 
 
 


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APPENDICES 
Appendix A: Schedule of Study Procedures and Evaluations 
Appendix B: List of Potentially Immune-Mediated Medical Conditions 


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APPENDIX A. SCHEDULE OF STUDY PROCEDURES AND 
EVALUATIONS 
Vaccination Period 
Study Visit Number 
V00 
V01 
V02** 
V03 
V04 
V05** 
V06 
V07 
Study Day post 1st  
vaccination 
Screening 
(Optional) 
D -28 to -
1 
Enrollment  
Dose 1 
D1 
D4±1d 
D8+2d 
D22+7d 
D25 
D29 
D43 
Study Day post 2nd vaccination 
 
 
 
 
Dose 2 
D1 
D4±1d 
D8+2d 
D22+7d 
Study Procedure/Evaluation 
Obtain Informed Consent∞ 
X 
X¬ 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X†¬1 
 
 
X†1 
 
 
 
Medical History@ 
X 
X†¬ 
X 
X 
X† 
X 
X 
X 
Concomitant Medications 
Xς 
X†¬ς 
Xς 
Xς 
X†ς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral Temperature%, Pulse, and 
BP) 
X 
X† 
 
 
X†2 
 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
Physical Examination3 
X 
X†* 
 
{X} 
{X}† 
 
{X} 
{X} 
Urine or Serum Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
 
Venous Blood Collection for 
ESR 
X≠ 
X≠* 
 
 
 
 
 
 
Venous Blood Collection for 
Clinical Safety Laboratory 
Evaluations~ 
 
X† 
 
X 
X† 
 
X 
 
Venous Blood Collection for 
Immunogenicity Assays 
 
X† 
 
X 
X†Ψ 
 
X 
X 
Serum Sample Collected for 
Future Research4 
 
X† 
 
X 
X† 
 
X 
X 
Enrollment in AdvantageEDCSM 
and Randomization 
 
X† 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity Assessments 
 
X† 
 
 
X† 
 
 
 
Study Vaccination 
 
X 
 
 
X 
 
 
 
20-minute Evaluation After 
Study Vaccination 
 
X 
 
 
X 
 
 
 
Examine Study Vaccination Site 
 
X 
 
X 
X 
 
X 
 
Post-Administration 
Reactogenicity Assessments 
 
X 
 
 
X 
 
 
 
Distribute Memory Aid and 
Study-Related Materials 
 
X 
 
 
X 
 
 
 
Review Memory Aid 
 
 
X 
X 
 
X 
X 
 
AE/SAE Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
X 
 
 
 


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** Phone call assessment 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened 
@ Complete medical history will be obtained by interview of subjects at the first visit (either screening [optional] or on Day 1 
prior to the first study vaccination) and interim medical history will be obtained by interview of subjects at subsequent visits . 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
* Not required if done at the optional screening visit 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the second study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to 
include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
and nervous system and as an assessment for signs suggestive of a PIMMC. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 hours prior 
to each study vaccination and results must be negative and known prior to each study vaccination. 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first study 
vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr 
Ψ  Subjects who do not receive the second study vaccination will continue with follow-up safety assessments (may be conducted 
by phone call) rather than in person continuing through approximately 12 months after their first study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 180 
days after their first study vaccination 
4 For subjects who have consented to collection of serum for future use either by signing an informed consent form that 
includes collection of future use samples as a condition of study participation or by indicating that they opt in to sample 
collection for future use if the informed consent form allows the option to choose that option. 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after each study 
vaccination.  
 
 
 


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Follow-Up Period (Including early termination and unscheduled visits) 
Study Visit Number 
V08** 
V09** 
V10 
V11** 
Early Termination (if 
needed) 
Unscheduled (if needed) 
Study Day post first 
study vaccination 
D82 
D142 
D202 
D387 
Study Day post second 
study vaccination 
D61±7d 
D121±14
d
D181±14
d 
D366±14
d
Study Procedure/Evaluation 
Medical History@ 
 
 
X 
 
X 
X (if indicated) 
Concomitant 
Medications 
Xς 
Xς 
Xς 
 
X (if within 21 days after last study 
vaccination and receipt of any non-
study influenza vaccine will be 
recorded if within 180 days after 
the 2nd study vaccination) 
X (if prior to 21 days after last 
study vaccination and receipt of 
any non-study influenza vaccine 
will be recorded if within 180 
days after the 2nd study) 
Vital Signs 
(Oral Temperature%, 
Pulse, and BP) 
 
 
 
 
X (may be obtained if indicated) 
X (may be obtained if indicated) 
Physical Examination3 
 
 
{X} 
 
{X} 
{X} 
Venous Blood 
Collection for Clinical 
Safety Laboratory 
Evaluations~ 
 
 
 
 
X (if within 7 days after the last 
study vaccination) 
X (if indicated) 
Venous Blood 
Collection for 
Immunogenicity Assays 
 
 
XΨ 
 
X (if within 21 days after last study 
vaccination) 
X (if prior to 21 days after last 
study vaccination) 
Serum Sample 
Collected for Future 
Research4 
 
 
X 
 
X(if within 21 days after last study 
vaccination 
X(if prior to 21 days after last 
study vaccination 
Examine Study 
Vaccination Site 
 
 
 
 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last 
study vaccination) 
Post-Administration 
Reactogenicity 
Assessments 
 
 
 
 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last 
study vaccination) 
Review Memory Aid 
 
 
 
 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last 
study vaccination) 
AE/SAE Assessment 
X# 
X# 
X# 
X# 
X# 
X# 
 
 
 


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** Phone call assessment 
@ Complete medical history will be obtained by interview of subjects at the first visit (either screening [optional] or on Day 1 
prior to the first study vaccination) and interim medical history will be obtained by interview of subjects at subsequent  visits . 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr 
Ψ  Subjects who do not receive the second study vaccination will continue with follow-up safety assessments (may be conducted 
by phone call) rather than in person continuing through approximately 12 months after their first study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 180 
days after their first study vaccination 
4 For subjects who have consented to collection of serum for future use either by signing an informed consent form that 
includes collection of future use samples as a condition of study participation or by indicating that they opt in to sample 
collection for future use if the informed consent form allows the option to choose that option. 
# AEs will be limited to SAEs and MAAEs, including NOCMCs and PIMMCs if after 21 days after last study vaccination 
 
 
 
 


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APPENDIX B. LIST OF POTENTIALLY IMMUNE-MEDIATED 
MEDICAL CONDITIONS 
(also known as Adverse Events of Special Interest (AESIs)) 
 
Gastrointestinal disorders 
• 
Celiac disease 
• 
Crohn’s disease 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
Liver disorders 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
Metabolic diseases 
• 
Addison’s disease 
• 
Autoimmune thyroiditis (including Hashimoto thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave's or Basedow’s disease 
Musculoskeletal disorders 
• 
Antisynthetase syndrome 
• 
Dermatomyositis 
• 
Juvenile chronic arthritis (including Still’s disease) 
• 
Mixed connective tissue disorder 
• 
Polymyalgia rheumatic 
• 
Polymyositis 
• 
Psoriatic arthropathy 
• 
Relapsing polychondritis 
• 
Rheumatoid arthritis 
• 
Scleroderma, including diffuse systemic form and CREST syndrome 
• 
Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter's Syndrome) 
and undifferentiated spondyloarthritis 
• 
Systemic lupus erythematosus 


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• 
Systemic sclerosis 
Neuroinflammatory disorders 
• 
Acute disseminated encephalomyelitis, including site specific variants (e.g., non-
infectious encephalitis, encephalomyelitis, myelitis, myeloradiculomyelitis) 
• 
Cranial nerve disorders, including paralyses/paresis (e.g., Bell’s palsy) 
• 
Guillain-Barré syndrome, including Miller Fisher syndrome and other variants 
• 
Immune-mediated peripheral neuropathies and plexopathies, including chronic 
inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and 
polyneuropathies associated with monoclonal gammopathy 
• 
Multiple sclerosis 
• 
Narcolepsy 
• 
Optic neuritis 
• 
Transverse myelitis 
• 
Myasthenia gravis, including Eaton-Lambert syndrome 
Skin disorders 
• 
Alopecia areata 
• 
Autoimmune bullous skin diseases, including pemphigus, pemphigoid and dermatitis 
herpetiformis 
• 
Cutaneous lupus erythematosus 
• 
Erythema nodosum 
• 
Morphoea 
• 
Lichen planus 
• 
Psoriasis 
• 
Sweet’s syndrome 
• 
Vitiligo 
Vasculitides 
• 
Large vessels vasculitis including: giant cell arteritis such as Takayasu's arteritis and 
temporal arteritis 
• 
Medium sized and/or small vessels vasculitis including: polyarteritis nodosa, Kawasaki's 
disease, microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome 
(allergic granulomatous angiitis), Buerger’s disease thromboangiitis obliterans, 
necrotizing vasculitis and anti-neutrophil cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified), Henoch- Schonlein purpura, Behcet's syndrome, 
leukocytoclastic vasculitis 
 


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Others 
• 
Antiphospholipid syndrome 
• 
Autoimmune hemolytic anemia 
• 
Autoimmune glomerulonephritis (including IgA nephropathy, glomerulonephritis rapidly 
progressive, membranous glomerulonephritis, membranoproliferative glomerulonephritis, 
and mesangioproliferative glomerulonephritis) 
• 
Autoimmune myocarditis/cardiomyopathy 
• 
Autoimmune thrombocytopenia 
• 
Good pasture syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Pernicious anemia 
• 
Raynaud’s phenomenon 
• 
Sarcoidosis 
• 
Sjögren’s syndrome 
• 
Stevens-Johnson syndrome 
• 
Uveitis 
 

SAP_001.pdf: 
 
CLINICAL RESEARCH IN INFECTIOUS DISEASES 
 
 
 
STATISTICAL ANALYSIS PLAN 
for 
DMID Protocol  
17-0075: A Phase II Study in Healthy Adults 19 Years and Older to Assess 
the Safety, Reactogenicity and Immunogenicity of a Sanofi Pasteur 
A/H7N9 Inactivated Influenza Vaccine Administered Intramuscularly 
With or Without AS03 Adjuvant  
 
 
 
 
17-0075: NCT03312231 
 
Version 2.0 
 
DATE: 26 August 2019 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 


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Version 2.0 
 
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STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 17-0075  
Development Phase: 
Phase II 
Products: 
Sanofi A/H7N9 Inactivated Influenza Vaccine  
GSK AS03 Adjuvant 
Form/Route: 
IM 
Indication Studied: 
Influenza A/H7N9 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
14 February 2018 
 
Clinical Trial Completion Date: 
Expected September 2019 
 
Date of the Analysis Plan: 
26 August 2019 
Version Number: 
2.0 
This study was performed in compliance with Good Clinical Practice. 
Information contained in this publication is the property of Division of Microbiology and Infectious Diseases and is 
confidential. This information may not be disclosed to third parties without written authorization from Division of 
Microbiology and Infectious Diseases. This report may not be reproduced, stored in a retrieval system or transmitted in any 
form or by any means - electronic, mechanical, recording or otherwise - without the prior authorization from Division of 
Microbiology and Infectious Diseases. This document must be returned to Division of Microbiology and Infectious Diseases 
upon request. 
 


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TABLE OF CONTENTS 
Study Title ................................................................................................................................................... ii 
TABLE OF CONTENTS ........................................................................................................................... iii 
List of Abbreviations .................................................................................................................................. vi 
1. 
PREFACE ............................................................................................................................................ 1 
2. 
INTRODUCTION ............................................................................................................................... 2 
2.1. 
Purpose of the Analyses ................................................................................................................ 2 
3. 
STUDY OBJECTIVES AND ENDPOINTS ....................................................................................... 3 
3.1. 
Study Objectives ........................................................................................................................... 3 
3.1.1. 
Primary ................................................................................................................................ 3 
3.1.2. 
Secondary ............................................................................................................................ 3 
3.2. 
Endpoints ...................................................................................................................................... 4 
3.2.1. 
Primary ................................................................................................................................ 4 
3.2.2. 
Secondary ............................................................................................................................ 5 
3.2.3. 
Exploratory .......................................................................................................................... 5 
3.3. 
Study Definitions and Derived Variables ..................................................................................... 6 
4. 
INVESTIGATIONAL PLAN .............................................................................................................. 7 
4.1. 
Overall Study Design and Plan ..................................................................................................... 7 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ........................................ 7 
4.3. 
Selection of Study Population ....................................................................................................... 8 
4.4. 
Treatments ..................................................................................................................................... 8 
4.4.1. 
Treatments Administered .................................................................................................... 8 
4.4.2. 
Identity of Investigational Product ...................................................................................... 8 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .............................. 8 
4.4.4. 
Selection of Doses in the Study ........................................................................................... 8 
4.4.5. 
Selection and Timing of Dose for Each Subject ................................................................. 8 
4.4.6. 
Blinding ............................................................................................................................... 8 
4.4.7. 
Prior and Concomitant Therapy .......................................................................................... 9 
4.4.8. 
Treatment Compliance ........................................................................................................ 9 
4.5. 
Immunogenicity and Safety Variables .......................................................................................... 9 
4.5.1. 
Safety Variables .................................................................................................................. 9 
4.5.2. 
Immunogenicity Variables ................................................................................................ 10 
5. 
SAMPLE SIZE CONSIDERATIONS .............................................................................................. 11 


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TABLE OF CONTENTS (continued) 
 
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6. 
GENERAL STATISTICAL CONSIDERATIONS ........................................................................... 12 
6.1. 
General Principles ....................................................................................................................... 12 
6.2. 
Timing of Analyses ..................................................................................................................... 12 
6.2.1. 
Expedited Interim Immunogenicity Reports ..................................................................... 12 
6.2.2. 
Preliminary Report and CSR ............................................................................................. 13 
6.3. 
Analysis Populations ................................................................................................................... 13 
6.3.1. 
Safety Population .............................................................................................................. 13 
6.3.2. 
Modified Intention-to-Treat (mITT) Population ............................................................... 13 
6.3.3. 
Per Protocol Population ..................................................................................................... 14 
6.4. 
Covariates and Subgroups ........................................................................................................... 14 
6.5. 
Missing Data ............................................................................................................................... 15 
6.6. 
Interim Analyses and Data Monitoring ....................................................................................... 15 
6.6.1. 
Interim Safety Review ....................................................................................................... 15 
6.6.2. 
Interim Immunogenicity Review....................................................................................... 16 
6.7. 
Multicenter Studies ..................................................................................................................... 16 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................................. 16 
7. 
STUDY SUBJECTS .......................................................................................................................... 17 
7.1. 
Subject Disposition ..................................................................................................................... 17 
7.2. 
Protocol Deviations ..................................................................................................................... 17 
8. 
IMMUNOGENICITY EVALUATION ............................................................................................ 18 
8.1. 
Primary Immunogenicity Analysis ............................................................................................. 18 
8.2. 
Secondary Immunogenicity Analyses ......................................................................................... 18 
8.3. 
Exploratory Immunogenicity Analyses....................................................................................... 18 
8.3.1. 
Covariate Analysis ............................................................................................................ 18 
8.3.2. 
Regression Modeling......................................................................................................... 19 
8.3.3. 
Analysis of Heterologous Strains ...................................................................................... 20 
8.3.4. 
NA Serum Antibody Responses ........................................................................................ 20 
9. 
SAFETY EVALUATION ................................................................................................................. 21 
9.1. 
Demographic and Other Baseline Characteristics ....................................................................... 21 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions ................................................... 21 
9.1.2. 
Prior and Concurrent Medications .................................................................................... 21 
9.2. 
Measurements of Treatment Compliance ................................................................................... 21 


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TABLE OF CONTENTS (continued) 
 
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9.3. 
Adverse Events ........................................................................................................................... 22 
9.3.1. 
Solicited Events and Symptoms ........................................................................................ 22 
9.3.2. 
Unsolicited Adverse Events .............................................................................................. 23 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ..................................... 24 
9.5. 
Pregnancies ................................................................................................................................. 24 
9.6. 
Clinical Laboratory Evaluations ................................................................................................. 24 
9.7. 
Vital Signs and Physical Evaluations .......................................................................................... 25 
9.8. 
Concomitant Medications ........................................................................................................... 25 
10. REPORTING CONVENTIONS ....................................................................................................... 26 
11. TECHNICAL DETAILS ................................................................................................................... 27 
12. SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED  
ANALYSES ...................................................................................................................................... 28 
13. REFERENCES .................................................................................................................................. 29 
14. Appendices ........................................................................................................................................ 30 
Appendix 1. 
Table Mock-Ups ................................................................................................................ 31 
Appendix 2. 
Figure Mock-Ups ............................................................................................................ 155 
Appendix 3. 
Listings Mock-Ups .......................................................................................................... 171 
 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
BP 
Blood Pressure  
C 
Celsius 
CI 
Confidence Interval 
Cr 
Creatinine 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
ELISA 
Enzyme-linked Immunosorbent Assay 
ER 
Emergency Room 
F 
Fahrenheit 
FDA 
U.S. Food and Drug Administration 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline 
HAI 
hemagglutination inhibition antibody 
Hgb 
Hemoglobin 
HHS 
U.S. Department of Health and Human Services 
ICH 
International Conference on Harmonisation 
IIV 
Inactivated Influenza Vaccine 
IM 
Intramuscularly 
IRB 
Institutional Review Board 
L 
Liter 
MAAE 
Medically Attended Adverse Event 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
mITT 
Modified Intention to Treat 
N, n 
Number  


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LIST OF ABBREVIATIONS (continued) 
 
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NA 
neuraminidase 
Neut 
Neutralizing Antibody 
NIH 
National Institutes of Health 
NOCMC 
New Onset Chronic Medical Condition 
PIMMC 
Potentially Immune Mediated Medical Condition 
PP 
Per Protocol 
PLT 
Platelets 
PT 
Preferred Term 
RCD 
Reverse Cumulative Distribution  
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
T. Bili 
Total Bilirubin 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 


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1. 
PREFACE 
This Statistical Analysis Plan (SAP) describes and expands upon the statistical information 
presented in the protocol.  
This document describes all planned analyses and provides reasons and justifications for 
these analyses. It also includes sample tables, figures, listings (TFLs) planned for (1) 
expedited interim immunogenicity analyses, (2) final analyses included in the preliminary 
report, and (3) analyses included in the Clinical Study Report (CSR). Regarding the final 
analyses and CSR, this SAP follows the International Conference on Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 
Guidelines, as indicated in Topic E3 (Structure and Content of Clinical Study Reports), and 
more generally is consistent with Topic E8 (General Considerations for Clinical Trials) and 
Topic E9 (Statistical Principles for Clinical Trials). The structure and content of the SAP 
provides sufficient detail to meet the requirements identified by the FDA and ICH, while all 
work planned and reported for this SAP will follow internationally accepted guidelines 
published by the American Statistical Association and the Royal Statistical Society for 
statistical practice.  
This document contains four sections: (1) a review of the study design, (2) general statistical 
considerations, (3) comprehensive statistical analysis methods for immunogenicity and safety 
outcomes, and (4) a list of proposed TFLs. Following any protocol amendment, this SAP will 
be reviewed and revised (if needed) to address any changes in the protocol impacting 
analysis. Any deviation from the final SAP will be described and justified in the CSR. The 
reader of this SAP is encouraged to also review the study protocol for details on conduct of 
the study and the operational aspects of clinical assessments. 


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2. 
INTRODUCTION 
Since March of 2013 [1], avian influenza A/H7N9 viruses have continued to circulate in 
China causing discrete outbreaks (or waves) in humans with high mortality over the past 5 
years. By late 2016, a fifth wave of outbreaks was identified in China and as of May 18, 
2017, a total of 1,463 laboratory-confirmed human infections with avian influenza A/H7N9 
virus have been reported by the World Health Organization [2, 3]. Since the onset of the fifth 
wave of H7N9 outbreaks in October 2016, more human cases of H7N9 infection have been 
reported in China than any prior H7N9 epidemic wave [3]. The U.S. Department of Health 
and Human Services (HHS) recently assessed H7N9 influenza virus as having a significant 
potential to cause a pandemic, and the greatest risk of causing severe disease. As a result, 
HHS has supported the production of fifth wave A/H7N9 inactivated influenza 9 vaccines 
(IIVs) for the U.S. stockpile and for an assessment of their safety and immunogenicity in 
clinical trials. 
The goal of this clinical trial is to assess in healthy adults the safety, reactogenicity, and 
immunogenicity of two doses of a monovalent inactivated influenza A/H7N9 virus vaccine 
administered IM at different dosages given with or without AS03 adjuvant and to evaluate 
the potential of the dosage levels and adjuvant to enhance the immune response to the 
A/H7N9 vaccine. The two doses of the A/H7N9 vaccine given with or without AS03 
adjuvant will be administered approximately 21 days apart. 
2.1. 
Purpose of the Analyses 
These analyses will assess the safety and immunogenicity of two doses of A/H7N9 IIV 
administered IM with or without AS03 adjuvant approximately 21 days apart and will be 
included in the clinical study report.  


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary 
Safety: 
• To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 
IIV administered IM at different dosages approximately 21 days apart given with or 
without AS03 adjuvant. 
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) 
antibody responses following receipt of two doses of 2017 H7N9 IIV administered 
IM at different dosages approximately 21 days apart with or without AS03 adjuvant, 
stratified by age of recipient. 
3.1.2. 
Secondary  
Safety: 
• To assess unsolicited non-serious adverse events (AEs) following receipt of two 
doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 
days apart with or without AS03 adjuvant. 
• To assess medically-attended adverse events (MAAEs) including new-onset chronic 
medical conditions (NOCMCs), potentially immune-mediated medical conditions 
(PIMMCs), and all serious adverse events (SAEs) following receipt of two doses of a 
2017 H7N9 IIV administered IM at different dosages approximately 21 days apart 
with or without AS03 adjuvant. 
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses approximately 7 and 21 days 
following receipt of a single dose, and approximately 7 days following receipt of two 
doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days 
apart with or without AS03 adjuvant, stratified by age of recipient. 
Exploratory: 
• To assess the effects of age, sex, body mass index, and prior receipt of seasonal 
influenza vaccine(s) on serum HAI and Neut antibody responses following receipt of 
two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 
21 days apart with or without AS03 adjuvant. 
• To assess, in at least a subset of samples, the cross-reactivity of serum HAI and Neut 
antibody responses to antigenically drifted variants of influenza A/H7 viruses 


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following receipt of two doses of a 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age 
of recipient.  
• To assess the durability of serum HAI and Neut antibody responses at approximately 
180 days following receipt of two doses of 2017 H7N9 IIV administered IM at 
different dosages approximately 21 days apart with or without AS03 adjuvant, 
stratified by age of recipient.  
• To assess the neuraminidase (NA) content of the 2017 H7N9 IIV and determine the 
serum antibody responses to NA following receipt of 2017 H7N9 IIV.  Note: analysis 
plans for this objective will be described in an addendum to this SAP once the NA 
assay has been selected. 
3.2. 
Endpoints 
3.2.1. 
Primary 
Safety: 
• Occurrence of study vaccine-related serious adverse events (SAEs) from the time of 
the first study vaccination through approximately 12 months after the last study 
vaccination. 
• Occurrence of solicited injection site and systemic reactogenicity events from the 
time of each study vaccination through 7 days after each study vaccination. 
• Occurrence of clinical safety laboratory adverse events from the time of each study 
vaccination through approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against the influenza 2017 H7N9 study vaccine strain (defined as either a pre-
vaccination titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer 
≥1:10 and a minimum four-fold rise in post-vaccination titer) at approximately 21 
days after the second study vaccination (Study Day 43). 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥1:40 against the 
influenza 2017 H7N9 study vaccine strain at approximately 21 days after the second 
study vaccination (Study Day 43). 
• Geometric Mean Titers (GMTs) of serum HAI and Neut antibodies against the 
influenza 2017 H7N9 vaccine strain at approximately 21 days after the second study 
vaccination (Study Day 43).  


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3.2.2. 
Secondary 
Safety: 
• Occurrence of study vaccine-related unsolicited non-serious AEs from the time of 
each study vaccination through approximately 21 days after each study vaccination. 
• Occurrence of all unsolicited adverse events, regardless of the assessment of 
seriousness or relatedness, from the time of each study vaccination through 
approximately 21 days after each study vaccination.  
• Occurrence of MAAEs, including NOCMCs, and PIMMCs from the time of the first 
study vaccination through approximately 12 months after the last study vaccination. 
• Occurrence of all serious adverse events (SAEs), regardless of the assessment of 
relatedness, from the time of the first vaccination through approximately 12 months 
after the last study vaccination.  
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against the influenza 2017 H7N9 vaccine strain at approximately 7, 21, and 28 days 
after the first study vaccination (Study Days 8, 22, 29). 
• For HAI and Neut antibodies, percentage of subjects achieving titers of 1:40 or 
greater against the influenza 2017 H7N9 vaccine strain at baseline and approximately 
7, 21, and 28 days after the first study vaccination (Study Days 8, 22, 29). 
• GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine 
virus at baseline and approximately 7, 21, and 28 days after the first study vaccination 
(Study Days 8, 22, 29).  
3.2.3. 
Exploratory 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion and 
the GMTs of serum HAI antibody against the 2017 H7N9 study vaccine strain 
approximately 21 and 180 days after the second study vaccination (Study Days 43 
and 202), stratified by age, sex, body mass index, and prior receipt of seasonal 
influenza vaccine(s). 
• For HAI and Neut antibodies, for at least a subset of subjects, percentage achieving 
seroconversion, percentage with titer ≥1:40, and GMTs against antigenically drifted 
variants of influenza A/H7 viruses at baseline and approximately 21 and 180 days 
after the second study vaccination (Study Day 43 and 202). 


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• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40, and GMTs against the 2017 H7N9 study vaccine strain at 
approximately 180 days after the second study vaccination (Study Day 202). 
• Percentage of subjects with detectable levels of serum N9 NA specific antibody 
elicited by 2017 H7N9 vaccination, and the correlation of the NA content of 2017 
H7N9 IIV with the elicited NA specific antibody responses at baseline and 
approximately 8 and 21 days after the first study vaccination (Study Day 1, 8 and 22) 
and 8, 21 and 180 days after the second study vaccination (Study Day, 29, 43 and 
202). Note: analysis plans for this endpoint will be described in an addendum to this 
SAP once the NA assay has been selected. 
3.3. 
Study Definitions and Derived Variables 
For individual subjects, fold rise will be calculated as the ratio of: 
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡
𝑝𝑝𝑟𝑟𝑒𝑒−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡, where 
pre-vaccination value is always the result obtained at Day 1, prior to the priming vaccination. 
HAI Seroconversion is defined as either a pre-vaccination HAI titer <10 and a post-
vaccination HAI titer ≥40 or a pre-vaccination HAI titer ≥10 and a minimum four-fold rise in 
post-vaccination HAI titer [5]. 
Neut Seroconversion is defined as either a pre-vaccination Neut titer <1:10 and a post-
vaccination Neut titer ≥1:40 or a pre-vaccination Neut titer ≥1:10 and a minimum four-fold 
rise in post-vaccination Neut antibody titer. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
The protocol follows a Phase II randomized, double blind study design enrolling males and 
non-pregnant females aged 19 years and older who are in good health as determined by 
medical history and physical examination, and meet all eligibility criteria, including 
erythrocyte sedimentation rate (ESR), hematology, and biochemistry parameter within 
acceptable range, negative urine or serum pregnancy test (for females). This clinical trial is 
designed to assess the safety, reactogenicity, and immunogenicity of a monovalent 
inactivated influenza A/H7N9 virus vaccine at different dosages (3.75 mcg, 7.5 mcg, 15 mcg 
of HA per dose) with AS03 adjuvant, or at different dosages (15 mcg and 45 mcg of HA per 
dose) without adjuvant.  
In this trial, subjects will be stratified by age (19-64 years or ≥65 years) then randomly 
assigned to 1 of 5 study groups with allocation 2:2:2:1:1 (see Table 1). The same dosage of 
vaccine with or without the same adjuvant will be given to subjects at both of their first and 
second study vaccinations. All study vaccinations will be administered IM approximately 21 
days apart. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study 
vaccination. Unsolicited non-serious AEs will be collected from the time of each study 
vaccination through approximately 21 days after each study vaccination. SAEs, MAAEs, 
including NOCMCs, and PIMMCs, will be collected from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. Clinical 
laboratory evaluations for safety will be performed on venous blood collected prior to each 
study vaccination and approximately 7 days after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 
2017 A/H7N9 vaccine virus and drifted variants of the A/H7N9 virus on serum samples 
obtained immediately prior to each study vaccination (Days 1 and approximately Day 22), 
approximately 7 days after each study vaccination (Days 8 and 29), and approximately 21 
and 180 days after the second study vaccination (Days 43 and 202). 
Novel methods for identifying and assessing alternative correlates of protection against 
influenza infection are needed. To assess the NA specific antibody response to vaccination, it 
is first necessary to determine the NA content of inactivated influenza vaccine; this assay is 
under development. If successful, the NA content in a dosage specific manner can be 
correlated to the N9 NA-specific antibody responses elicited by the 2017 H7N9 IIV. 
4.2. 
Discussion of Study Design, Including the Choice of Control 
Groups 
This study uses a dose comparison concurrent control design. All subjects receive the same 
study product (A/H7N9 IIV) with differing dosages with or without adjuvants. 


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4.3. 
Selection of Study Population 
The study population for this clinical trial is 640 males and non-pregnant females (with over-
enrollment up to 720 allowed), 19 years and older, who are in good health and meet all 
eligibility criteria. The subjects will be recruited from the general population at the 
participating Vaccine Trial and Evaluation Unit (VTEU) sites that have substantial 
experience conducting large influenza vaccine studies. 
4.4. 
Treatments 
4.4.1. 
Treatments Administered  
A/H7N9 Vaccine and AS03 Adjuvant will be administered. 
4.4.2. 
Identity of Investigational Product 
See the study protocol for details of study product formulation. 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) 
Enrollment/randomization will be performed through the enrollment module in the electronic 
data capture system maintained by the Statistical and Data Coordinating Center (SDCC).  
Eligible subjects will be stratified by clinical site and age (19-64 years, ≥65 years) then 
randomly assigned with allocation (2:2:2:1:1) to one of 5 treatment arms indicated in 
Table 1. The treatment sequence was generated using permuted block randomization to 
provide an approximately balanced allocation to the treatment arms during the study. 
4.4.4. 
Selection of Doses in the Study 
Participants in this study are to receive two A/H7N9 vaccinations at HA doses of 3.75, 7.5, or 
15 mcg with AS03 adjuvant, or at HA doses of 15 or 45 mcg without adjuvant. The 3.75, 7.5, 
or 15 mcg with AS03 doses are selected to evaluate safety and immunogenicity of antigen 
sparing dose strategies.  Per FDA Guidance [5], the 15 mcg non-adjuvanted dose was 
selected to compare immune response with the 15 mcg adjuvanted vaccine.  The 45 mcg non-
adjuvanted dose is included to confirm the expected poor immunogenicity of non-adjuvanted 
vaccine at a high dose. 
4.4.5. 
Selection and Timing of Dose for Each Subject 
Each subject is to be randomly assigned to a study group which will define the A/H7N9 
vaccine dose and receipt of adjuvant for both planned study vaccinations. The first 
vaccination takes place on the day of randomization, and the second vaccination takes place 
approximately 21 days after the first vaccination (protocol defined window of 21-28 days 
post first vaccination). 
4.4.6. 
Blinding 
This trial is double-blinded; subjects, investigators, study personnel performing any study-
related assessments following study vaccine administration, and laboratory personnel 
performing antibody assays are blinded to dosage within study vaccination schedule. 


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The randomization scheme was generated by the SDCC and provided to unblinded study 
personnel (i.e., pharmacists performing study vaccination preparations and unblinded study 
vaccine administrators) at the participating VTEU sites who will not be not involved in 
study-related assessments or have subject contact for data collection following study vaccine 
administration. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented 
by group. The DSMB may also be provided with expected and observed rates of the expected 
AEs in an unblinded fashion, and may request treatment assignment be unblinded for an 
individual subject if required for safety assessment. The DSMB will review grouped and 
unblinded data in the closed session only. 
4.4.7. 
Prior and Concomitant Therapy 
Administration of any medications, therapies, or vaccines (including prescription and over-
the-counter drugs as well as herbals, vitamins, and supplements) from 60 days prior to study 
vaccination through 21 days post final vaccination will be solicited from the participant 
during screening, enrollment, and follow-up. Any reported prior therapies from up to 30 days 
prior to vaccination through 21 days post final vaccination will be recorded in the appropriate 
data collection form.  
Use of concomitant medications is allowed prior to and during the trial with the exception of 
medications and therapies that might interfere with the evaluation of the investigational 
product. Medications in this category include the prohibited medication per the Subject 
Exclusion Criteria (protocol Section 5.1.2). In addition, the site principal investigator or 
appropriate sub-investigator may identify other medications that should not be used due to a 
risk to subject safety or assessment of reactogenicity and immunogenicity. 
4.4.8. 
Treatment Compliance 
All subjects were to receive two doses of study product administered in the clinic. 
4.5. 
Immunogenicity and Safety Variables 
See Table 2 and Table 3 for schedule of study procedures. 
4.5.1. 
Safety Variables 
Safety will be assessed by the frequency and severity of: 
1. SAEs occurring from the time of the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study 
vaccination through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, 
induration/swelling, pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. 


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3. Clinical safety laboratory AEs occurring from the time of each study vaccination 
through approximately 7 days after each study vaccination. Parameters to be 
evaluated include white blood cells (WBC), hemoglobin (Hgb), platelets (PLT), 
alanine aminotransferase (ALT), total bilirubin (T. Bili), and creatinine (Cr). 
4. Unsolicited AEs – non-serious AEs occurring from the time of each study vaccination 
through approximately 21 days after each study vaccination. 
5. MAAEs, including NOCMCs, and PIMMCs occurring from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. 
Grading scales for injection site and systemic solicited reactions, vital signs, and clinical 
laboratory parameters are provided in Table 10, Table 11, Table 12, and Table 13. 
4.5.2. 
Immunogenicity Variables 
Individual HAI and Neut results will be reported by the central immunology laboratory for 
the homologous vaccine strain, A/Hong Kong/125/2017 (H7N9), and heterologous H7N9 
strains (A/Shanghai/2/2013 and A/Guangdong/17SF003/2016). Assay results are reported as 
a reciprocal titer with values of 10*2k, where k=0, 1, 2, etc. The lower limit of detection for 
the HAI and Neut assays is 1:10; values below the limit of detection are imputed for analysis 
as one-half the limit of detection (10/2 = 5). For analysis, the geometric mean (calculated on 
natural log scale) of repeated results for each sample will be computed and used as the 
response for all subsequent calculations. The variation arising from multiple measurements 
for an individual at a single time point is not used in subsequent calculations. See Section 3.3 
for definitions of derived variables for the analysis of HAI and Neut data. 
The assay to determine the influenza virus N9 Neuraminidase (NA) antibody response to 
vaccination is under development. An addendum to the SAP will be generated to outline the 
planned analyses when assay development is complete.  
All immunogenicity data will be uploaded into the SDCC’s electronic data capture system. 


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5. 
SAMPLE SIZE CONSIDERATIONS 
This study is planned to enroll a minimum of 160 subjects in each adjuvanted treatment arm 
(100 in 19-64 years age stratum, 60 in ≥65 years stratum), and 80 subjects in each 
unadjuvanted treatment arm (50 in 19-64 years age stratum, 30 in ≥65 years stratum). The 
sample size for this study was selected to obtain preliminary estimates in a time critical 
manner. While this study is not designed to test any specific null hypothesis, the following 
tables illustrate the precision and power that is available for select estimates and comparisons 
of interest. 
Table 4 indicates the probability of observing one or more safety events, such as solicited 
injection site or systemic reactogenicity events or an unsolicited non-serious AE of a 
particular type for a single adjuvanted treatment arm/stratum (N = 60, or 100), for a single 
adjuvanted treatment arm combined over age strata (N=160), for all subjects receiving 
unadjuvanted vaccine (N = 160), and for all subjects receiving adjuvanted vaccine (N = 480). 
Binomial confidence intervals (CI) are widest (have the least precision) when the response 
rate is 50%. Table 5 is presented to indicate the worst case scenario for precision of observed 
exact (Clopper-Pearson) binomial confidence intervals. 
Table 6 illustrates the minimum detectable differences in the proportion of subjects 
responding (e.g., attaining seroconversion or a titer ≥1:40) between two adjuvanted treatment 
arms within each stratum using a two-sided Likelihood Ratio Test and alpha = 0.05. 
Over enrollment is allowed, to ensure a minimum of n=100 per adjuvanted treatment arm in 
the 19-64 years age stratum, therefore power calculations for this stratum assume n=100 per 
group. Based on previous DMID A/H7N9 trials it is expected 5% of enrolled subjects in this 
stratum may be excluded from analysis of the primary endpoint. In the event that only 100 
subjects are actually enrolled in a treatment arm, the small dropout rates anticipated would 
have a minimal impact on the calculations presented in Table 7.  
Within the ≥65 years treatment arm a dropout rate of up to 12% is expected based on 
previous DMID trials in this population, so a minimum of 60 subjects are planned to enroll in 
each adjuvanted treatment arm to ensure at least 50 are available for analysis of the primary 
immunogenicity endpoint. 
Per FDA guidance [5,6], for differences in HAI antibody response rates, the lower 
confidence limit on the appropriate point estimate excluding equality (i.e., 0 for the 
difference parameter) may be sufficient to demonstrate the added value of the adjuvant. 
Table 8 and Table 9 show the lower bound of the 95% confidence interval for the difference 
in the proportion of responders between the adjuvanted and unadjuvanted arms (e.g., 15 mcg 
+ AS03 minus 45 mcg unadjuvanted) assuming the proportion of responders in the 
unadjuvanted arm is 0.10 and considering a range for the proportion of responders in the 
adjuvanted arm ranges from 0.50 to 0.90.  


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
All continuous variables will be summarized using the following descriptive statistics: n 
(non-missing sample size), mean, standard deviation, median, maximum and minimum. The 
frequency and percentages (based on the non-missing sample size) of observed levels will be 
reported for all categorical measures. In general, all data will be listed, sorted by site, 
treatment and subject, and when appropriate by visit number within subject. All summary 
tables will be structured with a column for each treatment arm in the following order: 
• Group 1: 3.75 mcg A/H7N9 + AS03 
• Group 2: 7.5 mcg A/H7N9 + AS03 
• Group 3: 15 mcg A/H7N9 + AS03 
• Group 4: 15 mcg A/H7N9 
• Group 5: 45 mcg A/H7N9 
Additional tables structured with a column for each age stratum (19-64, ≥65) within 
treatment arm will be provided. All tables will be annotated with the total population size 
relevant to that table/treatment, including any missing observations. 
6.2. 
Timing of Analyses 
6.2.1. 
Expedited Interim Immunogenicity Reports 
A series of Expedited Interim Immunogenicity Reports of HAI and Neut serum antibody 
responses comparing venous blood samples collected at baseline (D1), Visit 03 (D8), Visit 
06 (D29), and Visit 07 (D43) is planned. Reports will include HAI and Neut results for 
approximately 25 subjects per adjuvanted treatment arm and 13 subjects per unadjuvanted 
treatment arm within the 19-64 year-old stratum and the first 15 subjects per adjuvanted 
treatment arm and 8 subjects per unadjuvanted treatment arm within the ≥65 year-old 
stratum. Reports will be prepared following each post-vaccination visit with analyses as 
described in Section 6.6.2. This information will be reviewed due to the extraordinary need 
to inform public health decision makers in their preparations for their response to a potential 
A/H7N9 pandemic. These data will be archived by the SDCC, but will not be part of the final 
clinical database for this study, nor will they be made available to the clinical investigators 
for publication. 
Expedited Immunogenicity Reports will be provided by the SDCC per the study 
Communication Plan. Reports will include data summarized by unblinded treatment arm, but 
the presentation will be in a format that prevents inadvertent unblinding of any individual 
subject.  
Tables and figures to be included in the Expedited Immunogenicity Report are indicated with 
the symbol † in the title. 


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6.2.2. 
Preliminary Report and CSR 
Clinical, safety, and reactogenicity data through approximately 180 days after the second 
study vaccination will represent the primary clinical database for this trial. Once the last 
subject completes the visit that occurs approximately 180 days after the last study 
vaccination, the primary clinical database will be cleaned, monitored, and locked, and all 
serum samples will be sent for HAI and Neut antibody assays. Unblinded analyses of safety, 
reactogenicity, and available immunogenicity data (HAI and Neut antibody assays through 
Day 202) are planned. A preliminary report may be prepared by the SDCC after the primary 
clinical database is locked and all HAI and Neut data through 180 days after the last study 
vaccination are received. Regardless of whether a preliminary report is prepared, a “topline” 
set of the immunogenicity tables will be provided to DMID on an expedited timeline 
following laboratory database lock. These analyses may be made available to the sponsor for 
planning subsequent trials and to the lead principal investigator for publication. These 
analyses will not be used to make any decisions concerning the conduct of this trial. As it is 
anticipated that subjects will remain in long term safety follow-up at the time of these 
analyses, blinded investigators and DMID medical monitors not involved in the analysis, 
publication, or clinical study report preparation will be responsible for assessing SAEs and 
MAAEs including PIMMCs and new onset chronic medical conditions until all subjects have 
completed the final follow-up visit. All analyses of data included in the preliminary report for 
early release will be considered the final analysis of these data, and also included in the final 
CSR.  
Tables and figures to be included in the Preliminary Report are indicated with the symbol * 
in the title. Topline tables to be generated after laboratory database lock are indicated with 
the symbol ‡ in the title. 
Analysis of exploratory immunogenicity endpoints may be performed and released as the 
data are available from the research laboratory. Any such analyses would be considered the 
final analysis for the endpoint and included in the CSR.  
The final CSR will be completed after the last subject’s last visit is completed, and the final 
clinical database including all long-term safety follow-up data is cleaned, monitored and 
locked. Additional exploratory immunogenicity endpoint data not available at the time of 
CSR preparation may be included in an addendum to the CSR. 
6.3. 
Analysis Populations 
6.3.1. 
Safety Population 
The Safety Analysis population includes all subjects who received at least one study 
vaccination. 
6.3.2. 
Modified Intention-to-Treat (mITT) Population 
The modified intent-to-treat (mITT) population includes all subjects who received at least 
one study vaccination and contributed both pre- and at least one post-study vaccination 
venous blood samples for immunogenicity testing (HAI or Neut antibody assays) for which 
valid results were reported. For analyses using the mITT population, subjects will be grouped 
based on randomized treatment arm.  


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6.3.3. 
Per Protocol Population 
The per protocol (PP) population includes all subjects in the mITT subset with the following 
exclusions: 
• Data from all available visits for subjects found to be ineligible at baseline due to 
eligibility criteria that would impact immune response. 
• Data from all visits subsequent to major protocol deviations, such as: 
o Second study vaccination not received, 
o Second study vaccination received out of window, 
o Receipt of non-study licensed live vaccine within 30 days before or after each study 
vaccination, 
o Receipt of non-study licensed inactivated vaccine within 14 days before or after 
each study vaccination, 
o Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before 
or after each study vaccination. 
• Data from any visit that occurs out of window by more than one day: 
o Visit 3 data collected before 6 days or after 10 days post first study vaccination 
o Visit 4 data collected before 20 days or after 29 days post first study vaccination. 
o Visit 6 data collected before 6 days or after 10 days post second study vaccination. 
o For subjects who did not receive the second study vaccination, visit 6 data 
collected before 27 days or after 31 days post first study vaccination. 
o Visit 7 data collected before 20 days or after 29 days post second study vaccination. 
o For subjects who did not receive the second study vaccination, visit 7 data 
collected before 41 days or after 50 days post first study vaccination. 
o Visit 10 data collected before 165 days or after 195 days post second study 
vaccination. 
o For subjects who did not receive the second study vaccination, visit 10 data 
collected before 200 days or after 216 days post first study vaccination. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received. 
6.4. 
Covariates and Subgroups 
As a protocol defined exploratory analysis, HAI antibody response following the second 
vaccination will be summarized stratified by the following covariates: age (categorical: 19-
34, 35-49, 50-64, 65-80, ≥80), sex (male, female), body mass index (<30, ≥30), and prior 


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receipt of seasonal influenza vaccine(s) (neither 2016-2017 nor 2017-2018, 2016-2017 only, 
2017-2018 only, both 2016-2017 and 2017-2018, unknown), and these covariates will be 
considered in statistical modeling as described in Section 8.3. As these analyses are 
exploratory the study was not powered for any subgroup analyses.  
6.5. 
Missing Data 
All attempts will be made to collect all data per protocol. As missing data are expected to be 
minimal, no imputation will be performed for missing values. Any data point that appears to 
be erroneous or inexplicable based on clinical judgment will be investigated as a possible 
outlier. If data points are identified as outliers, sensitivity analyses will be performed to 
examine the impact of including or excluding the outliers. Any substantive differences in 
these analyses will be reported. 
6.6. 
Interim Analyses and Data Monitoring 
Interim analyses will only be used to terminate this trial in the event that unanticipated safety 
events deemed to be of sufficient concern require such action by the sponsor. These 
assessments will not be made on the basis of testing a formal statistical hypothesis; therefore, 
p-value adjustment will not be made to any analyses. A DSMB will be convened by DMID 
to review study progress and participant, clinical, safety, and reactogenicity and 
immunogenicity data. 
An interim analysis of immunogenicity is planned, as described in section 6.2 which includes 
a series of Expedited Interim Immunogenicity Reports of serum HAI and Neut antibody 
responses. This information will be reviewed due to the extraordinary need to inform public 
health decision makers in their preparations for their response to a potential 2017 A/H7N9 
pandemic. Although interim immunogenicity results will not be used to make decisions 
concerning the conduct of this trial, they may be used to make decisions on activities external 
to this trial, e.g., designing future trials of the 2017 H7N9 IIV with and without AS03 
adjuvant in other age groups. 
Additionally, a preliminary report of safety and immunogenicity data through Day 43 will be 
prepared as described in section protocol section 11.6; though this report will be released 
while subjects remain in the trial for long-term safety and immunogenicity follow-up, it will 
be considered the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. 
If this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 
6.6.1. 
Interim Safety Review 
An interim safety review may include enrollment and demographic information, medical 
history, concomitant medications, physical assessments, clinical laboratory values, dosing 
compliance, and solicited and unsolicited AE/SAEs. Additional data may be requested by the 
DSMB, and interim statistical reports may be generated as deemed necessary and appropriate 
by DMID. The DSMB may receive data in aggregate and presented by treatment arm. The 


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DSMB may also be provided with expected and observed rates of the expected AEs in an 
unblinded fashion, and may request the treatment assignment be unblinded for an individual 
subject if required for safety assessment. The DSMB will review grouped and unblinded data 
in the closed session only. The DSMB will meet and review this data at scheduled time 
points or ad hoc as needed during this trial as defined in the DSMB charter. As an outcome 
of each review/meeting, the DSMB will make a recommendation as to the advisability of 
proceeding with study vaccinations (as applicable), and to continue, modify, or terminate this 
trial. Summaries prepared for the DSMB are defined separately in a report shell reviewed and 
approved by the DSMB. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Protocol Section 9.5 are met. 
6.6.2. 
Interim Immunogenicity Review 
There is no plan to halt this trial prior to full enrollment and completion of all follow-up 
visits based on interim immunogenicity results. A series of Expedited Interim 
Immunogenicity Reports of HAI and Neut serum antibody responses will be generated as 
described in Section 6.2. 
Immune responses will be summarized in terms of strain-specific 2017 A/H7N9 HAI and 
Neut antibody titers and the relationship to study vaccine dosage and adjuvant use. It is 
anticipated that all analyses will be carried out in parallel for both assays, but reports may be 
prepared separately for HAI and Neuts if results are available on different timelines. Interim 
analyses will focus on rates of titers ≥1:40, seroconversion (defined as either a pre-
vaccination titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and 
a minimum four-fold rise in post-vaccination titer) GMTs, along with corresponding 95% 
confidence intervals. No formal hypothesis testing will be included in the interim analysis. 
All interim analyses will use the mITT population. 
Tables and figures to be included in in the Expedited Interim Immunogenicity Reports are 
indicated with the symbol † in the title. These include Table 29 and Table 31 presenting 
summaries and 95% CIs of HAI and Neut antibodies respectively by treatment arm, Table 33 
and Table 35 presenting summaries and 95% CIs of HAI and Neut antibodies respectively by 
treatment arm and age stratum.  
6.7. 
Multicenter Studies 
Although randomization was stratified by site, data will be pooled across all clinical sites for 
all analyses. Center effects are not anticipated because the sites are using standardized 
procedures for vaccination and assessment of solicited and unsolicited AEs, and the study 
relies on a central laboratory for immunogenicity assessments. 
6.8. 
Multiple Comparisons/Multiplicity 
This study was designed to obtain preliminary estimates of safety and immune response to 
the A/H7N9 vaccination in healthy adults. The study was not designed to test any specific 
null hypothesis, and as such no adjustment for multiple comparisons will be performed. 


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7. 
STUDY SUBJECTS 
7.1. 
Subject Disposition 
Table 14 will present a summary of the reasons that subjects were screened but not enrolled. 
The number and percentage of enrolled subjects excluded from each analysis population by 
treatment arm and age stratum, are presented in Table 15 and Table 16. A listing of subjects 
excluded from each analysis population will be presented in Listing 5.  
The disposition of subjects in the study will be tabulated by treatment arm and age stratum 
(Table 17 and Table 18). The table will show the total number of subjects screened, 
randomized, receiving the first study vaccination, receiving the second study vaccination, 
completing the blood draw for the primary immunogenicity endpoints, and completing the 
last visit. 
A flowchart showing the disposition of study subjects, adapted from the CONSORT 
Statement [4] will be included and will present the number of subjects screened, randomized, 
lost to follow up, and analyzed, by treatment arm (Figure 1). 
A listing of subjects who were discontinued from treatment or terminated from study follow-
up and the reason will be included in Listing 2.   
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the deviation 
category and deviation type, treatment arm, and age stratum for all enrolled subjects 
(Table 9). Major deviations that will be reviewed for possible exclusion of immunogenicity 
results from the PP population include deviations related to eligibility/enrollment, treatment 
administration schedule, follow-up visit schedule, and receipt of exclusionary vaccines or 
medications. All subject-specific protocol deviations and non subject-specific protocol 
deviations will be included in Listing 3 and Listing 4. 


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8. 
IMMUNOGENICITY EVALUATION 
Immunogenicity data summaries and analysis for primary and secondary endpoints will be 
presented for the mITT and PP populations. Immune responses in terms of strain-specific 
A/H7N9 HAI and Neut antibody titers will be summarized by treatment arm and age stratum 
at each time point. Descriptive summary statistics will be provided for all assays and time 
points including number of subjects with non-missing results, percentage of subjects with 
titers ≥1:40, percentage of subjects achieving seroconversion, and GMTs along with 
corresponding 95% CI. Exact confidence intervals will be presented for proportional 
endpoints. Summaries of primary and secondary immunogenicity endpoints are presented in 
Table 29, Table 30, Table 31, Table 32, Table 33, Table 34, Table 35, and Table 36. 
RCD curves will be presented for post-vaccination HAI and Neut antibody titers. Plots for 
each assay will be generated with 4 panels (8 days post vaccination 1, 21 days post 
vaccination 1, 8 days post vaccination 2, 21 days post vaccination 2, and 180 days post 
vaccination 2), and separate curves within each panel for each treatment arm and age stratum, 
as shown in Figure 2, Figure 3, Figure 4, and Figure 5. 
Figures depicting the HAI and Neut GMT over time will also be presented as shown in 
Figure 6, Figure 7, Figure 8, and Figure 9. 
The spearman correlation between HAI, Neut, and Neuraminidase antibody titers will be 
calculated at each time point over all groups. The correlation will be depicted in scatter plots 
as Figure 10 and Figure 11. 
Individual HAI and Neut assay results will be provided in Listing 8. 
8.1. 
Primary Immunogenicity Analysis 
The primary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer ≥1:40, and GMTs against the homologous A/H7N9 vaccine strain 21 days 
after the second vaccination will be summarized as described above. Regression modelling of 
seroconversion and log titers is planned as described in Section 8.3.2. 
8.2. 
Secondary Immunogenicity Analyses 
The primary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer ≥40, and GMTs against the homologous A/H7N9 vaccine strain 8 and 21 
days after the first vaccination and 8 days after the second vaccination will be summarized as 
described above. No formal hypothesis testing is planned. 
8.3. 
Exploratory Immunogenicity Analyses 
Immunogenicity data summaries and analysis for exploratory endpoints will be presented for 
the PP populations. 
8.3.1. 
Covariate Analysis 
As an exploratory analysis, seroconversion and GMT of serum antibody for both HAI and 
Neut at 21 and 180 days after second vaccination will be summarized by treatment arm 
stratified by age (categorized as those subjects ages 19-34, 34-49, 50-64, 65-80, and ≥81 


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years) (Table 37, Table 38, Table 39, and Table 40), by sex (Table 41, Table 42, Table 43, 
and Table 44), by BMI (Table 45, Table 46, Table 47, and Table 48), and by prior receipt of 
seasonal influenza vaccines (Table 49, Table 50, Table 51, and Table 52). These stratified 
summaries will be presented for the PP population. It is anticipated that subjects will have 
little to no pre-existing antibody at baseline, so seroconversion and titer ≥ 40 endpoints will 
be similar. 
8.3.2. 
Regression Modeling 
Logistic and multivariate linear regression will be utilized to test for the effects of the HA 
antigen dose and the AS03 adjuvant on seroconversion and GMT, respectively, for the PP 
population. Similar models will be fit for HAI and Neut Antibodies. Separate models will be 
fit for data from Day 21 post dose 2 and Day 180 post dose 2.  
Logistic regression will be fit to examine the relationship of HAI seroconversion at 21 days 
after the 2nd study vaccination with treatment group and age strata (19-64 years, ≥65 years). 
If the available titer data meets the required assumptions of normality after log 
transformation, multiple linear regression will be fit to examine the relationship of log 
transformed titers at 21 days after the 2nd study vaccination with treatment arm and age strata 
(19-64 years, ≥65 years). Both models will be fit with and without adjustment for the 
following covariates (Z): sex (female, male), BMI (<30, ≥30), and prior receipt of seasonal 
influenza vaccine (none in past 2 seasons, at least once in past 2 seasons). Modeling 
assumptions will be checked using standard diagnostic methods (e.g., using the INFLUENCE 
option in PROC LOGISTIC or PROC GLM). Parameter estimates and odds ratio estimates 
for the logistic models will be presented in Table 53, Table 54, Table 55, Table 56, Table 57, 
Table 58, Table 59, and Table 60. Parameter estimates for the multiple linear regression 
models will be presented in Table 61, Table 62, Table 63, Table 64, Table 65, Table 66, 
Table 67, and Table 68. 
Model 1A: Logistic Regression (without covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 (𝐴𝐴𝐴𝐴𝑒𝑒≥65) + 𝜀𝜀 
Model 1B: Logistic Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 (𝐴𝐴𝐴𝐴𝐴𝐴≥65) + 𝛽𝛽3 × 𝑍𝑍+ 𝜀𝜀 
Model 2A: Multiple Linear Regression (without covariate adjustment): 
𝑙𝑙𝑜𝑜𝑜𝑜(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2(𝐴𝐴𝐴𝐴𝐴𝐴≥65) + 𝜀𝜀 
Model 2B: Multiple Linear Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2(𝐴𝐴𝐴𝐴𝐴𝐴≥65) + 𝛽𝛽3 × 𝑍𝑍+ 𝜀𝜀 
Subjects missing data for one or more covariates will be excluded from Models 1B and 2B. 
Models 1B and 2B, defined above, will also be fit for HAI at Day 21 replacing the binary age 
strata variable with age in years (continuous). The models as shown below assume a linear 
relationship between age in years and both probability of seroconversion and GMT. The 
validity of this assumption will be assessed prior to analysis and, if the relationship between 
age and response is found to be non-linear, adjustments will be made to model parameters to 


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satisfy regression assumptions. The results of these models will be presented in Table 69 and 
Table 70. 
Model 3: Logistic Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 (𝐴𝐴𝐴𝐴𝐴𝐴 𝑖𝑖𝑖𝑖 𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌) + 𝛽𝛽3 × 𝑍𝑍+ 𝜀𝜀 
Model 4: Multiple Linear Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2(𝐴𝐴𝐴𝐴𝐴𝐴 𝑖𝑖𝑖𝑖 𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌𝑌) + 𝛽𝛽3 × 𝑍𝑍+ 𝜀𝜀 
Subjects missing data for one or more covariates will be excluded from Models 3 and 4. 
8.3.3. 
Analysis of Heterologous Strains 
HAI and Neut antibody responses against antigenically drifted variants of influenza A/H7 
viruses (A/Shanghai/2/2013 and A/Guangdong/17SF003/2016) will be summarized for the 
Per Protocol population as described in Section 8  (Table 71 and Table 72; Figure 12, 
Figure 13, Figure 14, Figure 15, and Figure 16). A scatter plot of the correlation between 
response to the vaccine strain and each heterologous strain will be presented (Figure 17 and 
Figure 18). No formal hypothesis testing or modeling for the exploratory analysis of 
heterologous strains is planned.  
8.3.4. 
NA Serum Antibody Responses 
Descriptions of the NA assays and planned analyses will be described in an addendum to this 
SAP. 


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9. 
SAFETY EVALUATION 
All summaries and analysis of safety data will be presented for the Safety Analysis 
Population. Safety summaries will be presented overall and grouped by treatment arm overall 
and by age stratum. 
Continuous variables will be summarized using the following descriptive statistics: n (non-
missing sample size), mean, standard deviation, median, maximum and minimum. All 
categorical measures will be summarized by the frequency and percentages of observed 
levels. The denominator for the percentages may be based on the number of non-missing 
observations for an assessment or based on the number of subjects in a population. This will 
be described for each table. 
9.1. 
Demographic and Other Baseline Characteristics 
Summaries of age, sex, ethnicity, race, BMI, and prior receipt of seasonal influenza vaccine 
will be presented by site (Table 21 and Table 22) and by treatment arm overall and by age 
stratum (Table 23, Table 24, Table 25, and Table 26). Age will be summarized as a 
continuous variable as well as by strata categories. Ethnicity is categorized as Hispanic or 
Latino, or not Hispanic and not Latino. In accordance with NIH reporting policy, subjects 
may self-designate as belonging to more than one race or may refuse to identify a race, the 
latter reflected in the electronic case report form (eCRF) as “No” to each racial option. BMI 
will be summarized as a continuous as well as categorical variable, categorized as (<30, 
≥30). Self-reported history of prior receipt of seasonal influenza vaccine will be categorized 
as follows: neither 2016-2017 and 2017-2018, 2016-2017 only, 2017-2018 only, both 2016-
2017 and 2017-2018, or unknown. Demographic information for individual subjects will be 
provided in Listing 6. 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions 
All current illnesses and past or pre-existing medical conditions will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA®) version 20.0 or higher. 
Summaries of subjects’ prior and concurrent medical conditions will be presented by 
treatment arm (Table 27 and Table 28). 
Individual subject listings will be presented for all reported medical history including prior 
and concurrent medical conditions (Listing 7). 
9.1.2. 
Prior and Concurrent Medications  
Concomitant medications will be coded to the Anatomical Therapeutic Classification using 
the WHO Drug Dictionary. The use of concomitant medications during the study will be 
summarized by ATC1 and ATC2 code and treatment arm for the Safety population 
(Table 131 and Table 132). A listing of concomitant medications will be presented  
(Listing 16).  
9.2. 
Measurements of Treatment Compliance 
All subjects are to receive 2 study vaccinations administered in the clinic. The number of 
study vaccinations administered to subjects will be presented by treatment arm and by site, 


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overall and by age stratum in Table 19 and Table 20 and as part of the subject disposition 
tables (Table 17 and Table 18). Listing 1 presents subjects who received investigational 
product with randomized treatment arm and study product received for each vaccination. 
9.3. 
Adverse Events 
A summary of all adverse events is provided in Table 73. A summary of those events that 
occurred in ≥5% of subjects in any treatment group is provided in Table 74. 
9.3.1. 
Solicited Events and Symptoms 
Systemic solicited adverse events were collected pre-vaccination, and systemic and local 
solicited adverse events were collected at-least 20 minutes post-vaccination and then daily 
for 7 days after each vaccination and graded on a scale of 0 (absent), 1 (mild), 2 (moderate) 
and 3 (severe). Systemic events include fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. The grading scale for systemic events, including 
quantitative grading for fever, is included in Table 11. Local events include pruritus, 
ecchymosis, erythema, induration/swelling, pain, and tenderness. Ecchymosis, erythema, and 
induration are measured by both functional and measurement grading scales as defined in 
Table 10. 
When calculating the incidence of solicited events, each subject will be counted once at the 
highest severity following the applicable vaccination, and any repetitions will be ignored. For 
summaries presented separately for each vaccination, the denominator for percentages will be 
the number of subjects who received the respective vaccination with non-missing data for the 
event summarized. For summaries over all vaccinations the denominator will be the number 
of subjects who received at least one vaccination with non-missing data for the event 
summarized. 
The number and percentage of subjects reporting at least one solicited adverse event of any 
severity will be summarized for each solicited symptom, any systemic symptom, any local 
symptom, and any symptoms. For each event the denominator is the number of subjects who 
received the applicable vaccination with non-missing data for the specific event. The 95% CI 
calculated using Clopper-Pearson methodology from a binomial distribution (SAS Proc Freq 
with a binomial option) will be presented (Table 75, Table 76, Table 77, Table 78, Table 79, 
and Table 80).  Logistic regression models will be fit to estimate the effect of treatment and 
age on the probability of reporting any local event or reporting any systemic event (Table 81 
and Table 82). If statistically significant effects are observed in the model for local events or 
systemic events, then additional models will be fit for each individual event of that type. 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 (𝐴𝐴𝐴𝐴𝐴𝐴≥65) + 𝜀𝜀, 
For each systemic and local event, any systemic event, any local event, and any solicited 
event, the maximum severity over 7 days after each vaccination will be summarized for the 
Safety population. The number and percentage of subjects reporting each event will be 
summarized by the maximum severity and treatment group overall and by age stratum, 
separately for each vaccination and over all vaccinations. For each event the denominator is 
the number of subjects who received the applicable vaccination with non-missing data for the 
specific event. The 95% CI calculated using Clopper-Pearson methodology from a binomial 


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distribution (SAS Proc Freq with a binomial option) will be presented (Table 83, Table 84, 
Table 85, Table 86, Table 87, and Table 88). 
The number of subjects reporting a solicited adverse event will be summarized for each day 
post vaccination for each vaccination and for all vaccinations combined both in a summary 
table (Table 89, Table 90, and Table 91) and graphically in a bar chart (Figure 19 and 
Figure 20). A comparison of the event rate for each treatment group between vaccination 1 
and vaccination 2 will be presented, including p-values from McNemar’s test performed 
within each age stratum and over all subject (Table 92 and Table 93). 
Systemic and Local solicited events reported by subject will be presented in Listing 9 and 
Listing 10, sorted by subject ID, vaccination number, parameter, and study day. 
9.3.2. 
Unsolicited Adverse Events 
When calculating the incidence of unsolicited AEs (i.e., on a per subject basis), each subject 
will only be counted once at the highest severity and/or relationship, and any repetitions of 
AEs within a subject will be ignored; the denominator will be the total number of subjects in 
the safety population. All AEs reported will be included in the summaries and analyses. 
The number and percentage of subjects reporting at least one unsolicited AE will be 
summarized by MedDRA system organ class and preferred term. A 95% CI will be presented 
for the percentage of subjects reporting any unsolicited AE (serious or non-serious) for each 
MedDRA system organ class and preferred term over all study vaccinations (Table 94 and 
Table 95). 
The following summaries for unsolicited AEs will be presented by MedDRA system organ 
class, preferred term, and treatment arm: 
• Incidence of AEs by severity and relationship to study product (Table 96); 
• Incidence of non-serious, related AEs by severity (Table 97); 
• Incidence of AEs over time (Days 1-8, Days 9-22 post each study vaccination) 
(Table 98); 
• Incidence of non-serious, related AEs over time (Days 1-8, Days 9-22 post each study 
vaccination) (Table 99) – note this table presents results for secondary safety 
endpoint, “Occurrence of study vaccine-related unsolicited non-serious AEs from the 
time of each study vaccination through approximately 21 days after each study 
vaccination”; 
• Total frequency of AEs over time (Days 1-8, Days 9-22 post each study vaccination) 
(Table 100); 
• Subject listing of non-serious AEs of moderate or greater severity (Table 104);  
• Bar chart displaying total frequency of AEs by severity and MedDRA system organ 
class, Treatment Arm, and Age Stratum (Figure 21); 


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• Bar chart displaying incidence of AEs by severity and MedDRA system organ class, 
Treatment Arm, and Age Stratum (Figure 22); 
• Bar chart displaying total frequency and incidence of AEs by relationship to study 
product and MedDRA system organ class, Treatment Arm and Age Stratum 
(Figure 23 and Figure 24). 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse 
Events 
The following listings will be presented including Subject ID, Age (years) AE Description, 
AE Onset Date/End Date, Last Vaccination Received/Days Post Vaccination, Reason 
Reported as an SAE, Relationship to Treatment, Alternate Etiology if not Related, Outcome, 
and Duration of Event (days): 
• Deaths and Serious Adverse Events (Table 101); 
• Adverse Events of Special Interest (Table 102); 
• New Onset Chronic Medical Conditions (Table 103). 
A listing of all reported AEs by subject will be presented in Listing 11, sorted by Treatment 
Arm, Age Stratum, Subject ID, and AE Number. 
9.5. 
Pregnancies 
For any subjects in the Safety population who became pregnant during the study, every 
attempt will be made to follow these subjects to completion of pregnancy to document the 
outcome, including information regarding any complications with pregnancy and/or delivery. 
Listing 17, Listing 18, Listing 19, Listing 20, and Listing 21 will present any study 
pregnancies and their outcomes. 
9.6. 
Clinical Laboratory Evaluations 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, Cr) will be collected 
from each subject prior to each study vaccination and approximately 7 days after each study 
vaccination. These evaluations will be performed by the central clinical laboratory. The 
grading scale for clinical laboratory evaluations is presented in Table 13. Clinical laboratory 
evaluations assessed on Day 1 prior to the first study vaccination will be considered as 
baseline. 
The distribution of laboratory results by severity, study day, treatment arm and age stratum 
will be presented in Table 105, Table 106, Table 107, Table 108, Table 109, Table 110, and 
Table 111. Descriptive statistics including mean, standard deviation, median, minimum and 
maximum values by study day will be summarized for each parameter in Table 112, 
Table 113, Table 114, Table 115, Table 116, and Table 117, and for the change from baseline 
for each parameter in Table 118, Table 119, Table 120, Table 121, Table 122, and Table 123.  
Box plots illustrating the change from baseline for each laboratory parameter will be 
presented in Figure 25, Figure 26, Figure 27, Figure 28, Figure 29, and Figure 30. Subject 


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visits with abnormal laboratory results, Grade 1 severity or higher, will be presented in 
Table 124 and Table 125 for Chemistry and Hematology parameters, respectively. 
A complete listing of individual clinical laboratory results will be presented in Listing 12 and  
Listing 13 for chemistry and hematology, respectively, sorted by subject ID, parameter, and 
visit number. 
9.7. 
Vital Signs and Physical Evaluations 
Vital signs oral temperature, systolic blood pressure, diastolic blood pressure, and pulse will 
be assessed prior to study vaccination on Day 1 and Day 22. The grading scale for vital sign 
evaluations is presented in Table 12. Summaries of vital signs by maximum severity will be 
tabulated by visit, treatment arm, and age stratum (Table 126, Table 127, Table 128, 
Table 129, and Table 130). A listing of vital signs will be presented (Listing 14). 
Targeted physical examinations will be performed, if indicated, based on a subject’s medical 
history. A listing of physical exam findings will be presented (Listing 15). 
9.8. 
Concomitant Medications 
Concomitant medications will be collected for the 30 days prior to the first study vaccination 
through 21 days after the second study vaccination. Concomitant medications will be coded 
to the Anatomical Therapeutic Classification using the WHO Drug Dictionary. The use of 
prior and concomitant medications taken during the study will be recorded on the CRFs. A 
by-subject listing of concomitant medication use will be presented (Listing 16). The use of 
concomitant medications during the study will be summarized by ATC1, ATC2 code, 
treatment arm and age stratum for the Safety population (Table 131 and Table 132). 
 


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10. 
REPORTING CONVENTIONS 
P-values ≥0.001 and ≤0.999 will be reported to 3 decimal places; p-values less than 0.001 
will be reported as “<0.001”; p-values greater than 0.999 will be reported as “> 0.999“. The 
mean, standard deviation, and any other statistics other than quantiles, will be reported to one 
decimal place greater than the original data. Quantiles, such as median, or minimum and 
maximum will use the same number of decimal places as the original data. Proportions will 
be presented as two decimal places; values <0.01 will be presented as “<0.01”. Percentages 
will be reported to the nearest whole number; non-zero values < 1% will be presented as 
“<1”; values greater than 99% but less than 100% will be presented as >99. Estimated 
parameters, not on the same scale as raw observations (e.g. regression coefficients) will be 
reported to 3 significant figures.  


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11. 
TECHNICAL DETAILS 
SAS version 9.4 or above will be used to generate all tables, figures and listings. 


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12. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE 
STUDY OR PLANNED ANALYSES 
This SAP does not include any changes from the analyses described in the protocol. 


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13. 
REFERENCES 
1. Gao, R., et al., Human infection with a novel avian-origin influenza A (H7N9) virus. N 
Engl J Med, 2013. 368(20): p. 1888-97. 
2. Analysis of recent scientific information on avian influenza A(H7N9) virus. WHO 
Influenza Update, 2017. 
3. Human infection with avian influenza A(H7N9) virus – China: 18 May 2017. WHO 
Emergencies preparedness, response, 2017. 
4. Drummond R. CONSORT Revised: Improving the Reporting of Randomized Clinical 
Trials. JAMA. 2001; 285(15):2006-2007. 
5. FDA Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal 
Inactivated Influenza Vaccines (US DHHS, FDA, CBER, May 2007). 
6. FDA Guidance for Industry: Clinical Data Needed to Support the Licensure of 
Pandemic Influenza Vaccines (US DHHS, FDA, CBER, May 2007). 
 
 
 


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14. 
APPENDICES 
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. Tables and figures 
included in the expedited interim immunogenicity reports are indicated by †. Tables and 
figures included in the Preliminary Report are indicated by *. Topline tables are indicated by 
‡. 
 
 


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APPENDIX 1. TABLE MOCK-UPS 
LIST OF TABLES 
Table 1: 
Study Design ................................................................................................................ 38 
Table 2: 
Schedule of Study Procedures – Vaccination Period ................................................... 39 
Table 3: 
Schedule of Study Procedures - Follow-Up Period (Including early termination and 
unscheduled visits) ....................................................................................................... 41 
Table 4: 
Power (%) to Detect Safety Events .............................................................................. 43 
Table 5: 
Precisions of Binomial Confidence Intervals ............................................................... 43 
Table 6: 
Minimum Detectable Difference in Proportion Responders ........................................ 43 
Table 7: 
Lower Confidence Bound for Difference in Proportion of Responders  Between 
Adjuvanted (N = 100) and Unadjuvanted (N = 50) Arms, 19-64 Years Stratum ........ 44 
Table 8: 
Lower Confidence Bound for Difference in Proportion of Responders  Between 
Adjuvanted (N = 50) and Unadjuvanted (N = 25) Arms, ≥65 Years Stratum ............. 44 
Table 9: 
Distribution of Protocol Deviations by Category, Type and Treatment Arm, All 
Enrolled Subjects ......................................................................................................... 45 
Table 10: 
Solicited Adverse Event Grading Scale – Local .......................................................... 47 
Table 11: 
Solicited Adverse Event Grading Scale - Systemic ..................................................... 48 
Table 12: 
Vital Signs Adverse Event Grading Scale ................................................................... 49 
Table 13: 
Laboratory Adverse Event Grading Scale ................................................................... 50 
Table 14: 
Ineligibility Summary of Screen Failures* .................................................................. 51 
Table 15: 
Analysis Populations by Treatment Arm, All Enrolled Subjects* ............................... 52 
Table 16: 
Analysis Populations by Treatment Arm and Age Stratum, All Enrolled Subjects* ... 54 
Table 17: 
Subject Disposition by Treatment Arm, All Enrolled Subjects* ................................. 57 
Table 18: 
Subject Disposition by Treatment Arm and Age Stratum, All Enrolled Subjects* ..... 58 
Table 19: 
Dates of First Study Vaccination by Site, Treatment Arm, and Age Stratum, for Safety 
Analysis Population ..................................................................................................... 59 
Table 20: 
Dates of Second Study Vaccination by Site, Treatment Arm, and Age Stratum, for 
Safety Analysis Population .......................................................................................... 59 
Table 21: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All 
Enrolled Subjects ......................................................................................................... 60 
Table 22: 
Summary of Continuous Demographic and Baseline Characteristics by Site, All 
Enrolled Subjects ......................................................................................................... 62 
Table 23: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment 
Arm, All Enrolled Subjects* ........................................................................................ 63 
Table 24: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment 
Arm and Age Stratum, All Enrolled Subjects* ............................................................ 65 
Table 25: 
Summary of Continuous Baseline Characteristics by Treatment Arm, All Enrolled 
Subjects* ...................................................................................................................... 67 
Table 26: 
Summary of Continuous Baseline Characteristics by Treatment Arm and Age Stratum, 
All Enrolled Subjects* ................................................................................................. 68 
Table 27: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA 
System Organ Class and Treatment Arm, Safety Analysis Population ....................... 69 
Table 28: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA 
System Organ Class, Treatment Arm and Age Stratum, Safety Analysis Population . 70 
Table 29: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day and Treatment Arm, Modified Intent-to-Treat Population*†‡ ............................. 71 
Table 30: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day and Treatment Arm, Per Protocol Population*‡ .................................................. 72 
Table 31: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and 
Treatment Arm, Modified Intent-to-Treat Population*†‡ ........................................... 72 


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Table 32: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and 
Treatment Arm, Per Protocol Population*‡ ................................................................. 72 
Table 33: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day, Treatment Arm and Age Stratum, Modified Intent-to-Treat Population*†‡ ....... 73 
Table 34: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day, Treatment Arm and Age Stratum, Per Protocol Population*‡ ............................ 75 
Table 35: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day, Treatment 
Arm and Age Stratum, Modified Intent-to-Treat Population*†‡ ................................. 75 
Table 36: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day, Treatment 
Arm and Age Stratum, Per Protocol Population*‡ ...................................................... 75 
Table 37: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm and Age Categories at 21 Days Post Second Vaccination, Per-Protocol 
Population* .................................................................................................................. 76 
Table 38: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm and Age Stratum at 180 Days Post Second Vaccination, Per-Protocol 
Population* .................................................................................................................. 78 
Table 39: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm and 
Age Stratum at 21 Days Post Second Vaccination, Per-Protocol Population* ............ 78 
Table 40: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm and 
Age Stratum at 180 Days Post Second Vaccination, Per-Protocol Population* .......... 78 
Table 41: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and Sex at 21 Days Post Second Vaccination, Per-
Protocol Population* .................................................................................................... 79 
Table 42: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and Sex at 180 Days Post Second Vaccination, Per-
Protocol Population* .................................................................................................... 80 
Table 43: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and Sex at 21 Days Post Second Vaccination, Per-Protocol Population* ...... 80 
Table 44: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and Sex at 180 Days Post Second Vaccination, Per-Protocol Population* .... 80 
Table 45: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and BMI at 21 Days Post Second Vaccination, Per-
Protocol Population* .................................................................................................... 81 
Table 46: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and BMI at 180 Days Post Second Vaccination, Per-
Protocol Population* .................................................................................................... 82 
Table 47: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and BMI at 21 Days Post Second Vaccination, Per-Protocol Population* .... 82 
Table 48: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and BMI at 180 Days Post Second Vaccination, Per-Protocol Population* .. 82 
Table 49: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 21 Days 
Post Second Vaccination, Per-Protocol Population* ................................................... 83 
Table 50: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 180 Days 
Post Second Vaccination, Per-Protocol Population* ................................................... 84 
Table 51: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and Prior Seasonal Influenza Vaccination at 21 Days Post Second 
Vaccination, Per-Protocol Population* ........................................................................ 84 


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Table 52: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age 
Stratum and Prior Seasonal Influenza Vaccination at 180 Days Post Second 
Vaccination, Per-Protocol Population* ........................................................................ 84 
Table 53: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with HAI Seroconversion Against 2017 A/H7N9 at 21 Days Post 
Second Study Vaccination, Per Protocol Population* ................................................. 85 
Table 54: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with Neut Seroconversion Against 2017 A/H7N9 at 21 Days Post 
Second Study Vaccination, Per Protocol Population* ................................................. 86 
Table 55: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with HAI Seroconversion Against 2017 A/H7N9 at 180 Days Post 
Second Study Vaccination, Per Protocol Population* ................................................. 86 
Table 56: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with Neut Seroconversion Against 2017 A/H7N9 at 180 Days Post 
Second Study Vaccination, Per Protocol Population* ................................................. 86 
Table 57: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with HAI Seroconversion Against 2017 A/H7N9 at 21 Days Post 
Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 87 
Table 58: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with Neut Seroconversion Against 2017 A/H7N9 at 21 Days Post 
Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 88 
Table 59: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with HAI Seroconversion Against 2017 A/H7N9 at 180 Days Post 
Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 88 
Table 60: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with Neut Seroconversion Against 2017 A/H7N9 at 180 Days Post 
Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 88 
Table 61: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination, Per Protocol Population* ........................................................................ 89 
Table 62: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination, Per Protocol Population* ........................................................................ 90 
Table 63: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination, Per Protocol Population* ........................................................................ 90 
Table 64: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination, Per Protocol Population* ........................................................................ 90 
Table 65: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 91 
Table 66: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 92 


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Table 67: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 92 
Table 68: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 92 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
AS03 Adjuvant with HAI Seroconversion Against 2017 A/H7N9 at 21 Days Post 
Second Study Vaccination, Adjusted for Baseline Covariates and Age in Years, Per 
Protocol Population* .................................................................................................... 93 
Table 70: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and AS03 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates and Age in Years, Per Protocol 
Population* .................................................................................................................. 94 
Table 71: 
Summaries of Hemagglutination Inhibition Antibody Against Antigenically Drifted 
Variants by Study Day, Treatment Arm and Age Stratum, Per Protocol Population* 95 
Table 72: 
Summaries of Neutralizing Antibody Against Antigenically Drifted Variants by Study 
Day, Treatment Arm and Age Stratum, Per Protocol Population* .............................. 96 
Table 73: 
Overall Summary of Adverse Events  - Safety Population*‡ ...................................... 97 
Table 74: 
Number of Adverse Events Occurring in 5% of Subjects in Any Treatment Group by 
MedDRA System Organ Class and Preferred Term, and Treatment Group - Safety 
Population .................................................................................................................... 99 
Table 75: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Arm Post Any Study Vaccination – 
Safety Population* ..................................................................................................... 100 
Table 76: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Arm Post Study Vaccination 1 – 
Safety Population * .................................................................................................... 101 
Table 77: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Arm Post Study Vaccination 2 – 
Safety Population * .................................................................................................... 101 
Table 78: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Treatment Arm and Age Stratum Post Any Study 
Vaccination – Safety Population * ............................................................................. 102 
Table 79: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Treatment Arm and Age Stratum Post Study 
Vaccination 1 – Safety Population * .......................................................................... 105 
Table 80: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Treatment Arm and Age Stratum Post Study 
Vaccination 2 – Safety Population * .......................................................................... 105 
Table 81: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose, AS03 
Adjuvant, and Age with Reporting Any Local Event Post Any Study Vaccination – 
Safety Population * .................................................................................................... 106 
Table 82: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose, AS03 
Adjuvant, and Age with Reporting Any Systemic Event Post Any Study Vaccination 
(N=X) – Safety Population * ..................................................................................... 106 
Table 83: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Arm Post Any Study Vaccination – Safety 
Population * ............................................................................................................... 107 


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Table 84: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Arm Post Study Vaccination 1 – Safety Population 
* ................................................................................................................................. 111 
Table 85: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Arm Post Study Vaccination 2 – Safety Population 
* ................................................................................................................................. 111 
Table 86: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity, Treatment Arm and Age Stratum Post Any Study Vaccination – 
Safety Population * .................................................................................................... 112 
Table 87: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity, Treatment Arm and Age Stratum Post Study Vaccination 1 – 
Safety Population * .................................................................................................... 121 
Table 88: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity, Treatment Arm and Age Stratum Post Study Vaccination 2 – 
Safety Population * .................................................................................................... 121 
Table 89: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, Treatment Arm and Age Stratum Post Any 
Study Vaccination – Safety Population ..................................................................... 122 
Table 90: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, Treatment Arm and Age Stratum Post Study 
Vaccination 1 – Safety Population ............................................................................. 126 
Table 91: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, Treatment Arm and Age Stratum Post Study 
Vaccination 2 – Safety Population ............................................................................. 126 
Table 92: 
Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 
1 Compared with Dose 2 by Treatment Arm and Age Stratum – Safety Population 127 
Table 93: 
Number and Percentage of Subjects Experiencing Solicited Local Events for Dose 1 
Compared with Dose 2 by Treatment Arm and Age Stratum – Safety Population ... 130 
Table 94: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA System Organ Class and Preferred Term, and 
Treatment Arm – Safety Population * ....................................................................... 131 
Table 95: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA System Organ Class and Preferred Term, 
Treatment Arm and Age Stratum – Safety Population * ........................................... 132 
Table 96: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA System Organ Class and Preferred Term, Maximum Severity, Relationship, 
Treatment Arm and Age Stratum – Safety Population* ............................................ 133 
Table 97: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited 
Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum 
Severity, Treatment Arm and Age Stratum – Safety Population ............................... 134 
Table 98: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 
21 Days Post Study Vaccination by MedDRA System Organ Class and Preferred 
Term, Day Post Vaccination, Treatment Arm and Age Stratum – Safety Population135 
Table 99: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited 
Adverse Events Within 21 Days Post Vaccination by MedDRA System Organ Class 
and Preferred Term, Study Vaccination, Treatment Arm and Age Stratum – Safety 
Population .................................................................................................................. 136 
Table 100: 
Number of Unsolicited Adverse Events by MedDRA System Organ Class and 
Preferred Term, Day Post Vaccination, Treatment Arm and Age Stratum – Safety 
Population .................................................................................................................. 137 
Table 101: 
Listing of Serious Adverse Events – Safety Population * ......................................... 138 


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Table 102: 
Listing of Adverse Events of Special Interest – Safety Population * ........................ 139 
Table 103: 
Listing of New Onset Chronic Medical Conditions – Safety Population * ............... 139 
Table 104: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Safety 
Population * ............................................................................................................... 139 
Table 105: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group 
and Age Stratum, All Laboratory Parameters – Safety Population * ........................ 141 
Table 106: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group 
and Age Stratum,Hemoglobin – Safety Population * ................................................ 142 
Table 107: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group 
and Age Stratum, Alanine – Safety Population aminotransferase (ALT)* ................ 142 
Table 108: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group 
and Age Stratum, Total Bilirubin – Safety Population * ........................................... 142 
Table 109: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group 
and Age Stratum, Creatinine – Safety Population * .................................................. 142 
Table 110: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Arm and 
Age Stratum, White Blood Cells – Safety Population * ............................................ 143 
Table 111: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Arm and 
Age Stratum, Platelets – Safety Population * ............................................................ 144 
Table 112: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, White Blood Cells – Safety Population * .................................................... 145 
Table 113: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, Hemoglobin – Safety Population * ............................................................. 145 
Table 114: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, Platelets – Safety Population * .................................................................... 145 
Table 115: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, Alanine Aminotransferase – Safety Population * (ALT) ............................ 145 
Table 116: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, Total Bilirubin – Safety Population * .......................................................... 145 
Table 117: 
Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age 
Stratum, Creatinine – Safety Population * ................................................................. 146 
Table 118: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum, White Blood Cells – Safety Population * ............ 146 
Table 119: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum, Hemoglobin – Safety Population * ..................... 146 
Table 120: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum, Platelets – Safety Population * ............................ 146 
Table 121: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum, Alanine aminotransferase (ALT) – Safety 
Population * ............................................................................................................... 146 
Table 122: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum,  Total Bilirubin – Safety Population *................. 146 
Table 123: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, 
Treatment Arm and Age Stratum, Creatinine – Safety Population * ......................... 146 
Table 124: 
Listing of Abnormal Laboratory Results - Chemistry ............................................... 148 
Table 125: 
Listing of Abnormal Laboratory Results - Hematology ............................................ 149 
Table 126: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age 
Stratum, Any Assessment – Safety Population * ....................................................... 150 
Table 127: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age 
Stratum, Oral Temperature – Safety Population ........................................................ 150 
Table 128: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age 
Stratum, Systolic Blood Pressure – Safety Population .............................................. 151 


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Table 129: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age 
Stratum, Diastolic Blood Pressure – Safety Population ............................................. 152 
Table 130: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age 
Stratum, Pulse – Safety Population ............................................................................ 152 
Table 131: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Treatment Arm – Safety Population ................................... 153 
Table 132: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification, Treatment Arm and Age Stratum – Safety Population ............. 154 
 
 


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9.1  
Overall Study Design and Plan Description 
Table 1: 
Study Design 
Treatment 
Arms 
Stratum 
Day 1 
Study Vaccination 1 
Day 22 
Study Vaccination 2 
Group 1, n=160 
Age 19-64, n=100 
H7N9 vaccine 3.75 mcg plus 
AS03 adjuvant 
H7N9 vaccine 3.75 mcg plus 
AS03 adjuvant 
Age ≥ 65, n=60 
Group 2, n=160 
Age 19-64, n=100 
H7N9 vaccine 7.5 mcg plus 
AS03 adjuvant 
H7N9 vaccine 7.5 mcg plus 
AS03 adjuvant 
Age ≥ 65, n=60 
Group 3, n=160 
Age 19-64, n=100 
H7N9 vaccine 15 mcg plus 
AS03 adjuvant 
H7N9 vaccine 15 mcg plus AS03 
adjuvant 
Age ≥ 65, n=60 
Group 4, n=80 
Age 19-64, =50 
r H7N9 vaccine 15 mcg 
unadjuvanted 
H7N9 vaccine 15 mcg 
unadjuvanted 
Age ≥ 65, n=30 
Group 5, n=80 
Age 19-64, n=50 
H7N9 vaccine 45 mcg 
unadjuvanted 
H7N9 vaccine 45 mcg 
unadjuvanted 
Age ≥ 65, n=30 
Total Enrollment, 
n = 640 
Age 19-64, n=400* 
*Over enrollment up to 420 subjects may be allowed to ensure 
approximately 100 subjects in each AS03 adjuvanted treatment arm, 
and 50 subjects in each of the unadjuvanted treatment arm are 
eligible for inclusion in post Dose 2 immunogenicity analyses 
Age ≥ 65, n=240** 
**Over enrollment up to 300 subjects may be allowed to ensure 60 
subjects in each of the AS03 adjuvanted treatment arms, and 30 
subjects in each of the unadjuvanted treatment arms are eligible for 
inclusion in post Dose 2 immunogenicity analyses 
 
 


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9.5.1 Efficacy/Immunogenicity and Safety Measurements Assessed and Flow Chart 
Table 2: 
Schedule of Study Procedures – Vaccination Period 
Study Visit Number 
V00 
V01 
V02** 
V03 
V04 
V05** 
V06 
V07 
Study Day post 1st  
vaccination 
Screening 
(Optional) 
D -28 to -
1 
Enrollment 
Dose 1 
D1 
D4±1d 
D8+2d 
D22+7d 
D25 
D29 
D43 
Study Day post 2nd 
vaccination 
 
 
 
 
Dose 2 
D1 
D4±1d 
D8+2d 
D22+7d 
Study Procedure/Evaluation 
Obtain Informed Consent∞ 
X 
X¬ 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X†¬1 
 
 
X†1 
 
 
 
Medical History@ 
X 
X†¬ 
X 
X 
X† 
X 
X 
X 
Concomitant Medications 
Xς 
X†¬ς 
Xς 
Xς 
X†ς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral Temperature%, Pulse, 
and BP) 
X 
X† 
 
 
X†2 
 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
Physical Examination3 
X 
X†* 
 
{X} 
{X}† 
 
{X} 
{X} 
Urine or Serum Pregnancy 
Test 
X^ 
X†^ 
 
 
X†^ 
 
 
 
Venous Blood Collection for 
ESR 
X≠ 
X≠* 
 
 
 
 
 
 
Venous Blood Collection for 
Clinical Safety Laboratory 
Evaluations~ 
 
X† 
 
X 
X† 
 
X 
 
Venous Blood Collection for 
Anti-viral Antibody Assays 
 
X† 
 
X 
X†Ψ 
 
X 
X 
Serum Sample Collected for 
Future Research4 
 
X† 
 
X 
X† 
 
X 
X 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
X† 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity Assessments 
 
X† 
 
 
X† 
 
 
 
Study Vaccination 
 
X 
 
 
X 
 
 
 
20-minute Evaluation After 
Study Vaccination 
 
X 
 
 
X 
 
 
 
Examine Study Vaccination 
Site 
 
X 
 
X 
X 
 
X 
 
Post-Administration 
Reactogenicity Assessments 
 
X 
 
 
X 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 2: Schedule of Study Procedures – Vaccination Period (continued) 
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Study Visit Number 
V00 
V01 
V02** 
V03 
V04 
V05** 
V06 
V07 
Study Day post 1st  
vaccination 
Screening 
(Optional) 
D -28 to -
1 
Enrollment 
Dose 1 
D1 
D4±1d 
D8+2d 
D22+7d 
D25 
D29 
D43 
Study Day post 2nd 
vaccination 
 
 
 
 
Dose 2 
D1 
D4±1d 
D8+2d 
D22+7d 
Study Procedure/Evaluation 
Distribute Memory Aid and 
Study-Related Materials 
 
X 
 
 
X 
 
 
 
Review Memory Aid 
 
 
X 
X 
 
X 
X 
 
AE/SAE Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
X 
** Phone call assessment 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened 
@ Complete medical history will be obtained by interview of subjects at the first visit (either screening [optional] or on Day 
1 prior to the first study vaccination) and interim medical history will be obtained by interview of subjects at subsequent 
visits. 
ς Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, 
and reported in the eCRF. 
* Not required if done at the optional screening visit 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the second study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to 
include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ Will be performed on all women of childbearing potential at screening (optional) and within 24 hours prior to each study 
vaccination and results must be negative and known prior to each study vaccination. 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first 
study vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr 
Ψ Subjects who do not receive the second study vaccination will continue with follow-up safety assessments (may be 
conducted by phone call) rather than in person continuing through approximately 12 months after their first study 
vaccination. These subjects will also be encouraged to provide a venous blood sample for anti-viral antibody assays at 
approximately 21 and 180 days after their first study vaccination 
4 For subjects who have consented to collection of serum for future use 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after each study 
vaccination.  


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Table 3: 
Schedule of Study Procedures - Follow-Up Period (Including early termination and unscheduled visits) 
Study Visit Number 
V08** 
V09** 
V10 
V11** 
Early Termination (if needed) 
Unscheduled (if needed) 
Study Day post first 
study vaccination 
D82 
D142 
D202 
D387 
Study Day post second 
study vaccination 
D61±7d 
D121±14d 
D181±14d 
D366±14d 
Study Procedure/Evaluation 
Medical History@ 
 
 
X 
 
X 
X (if indicated) 
Concomitant Medications 
Xς 
Xς 
Xς 
 
X (if within 21 days after last 
study vaccination and receipt of 
any non-study influenza vaccine 
will be recorded if within 180 
days after the 2nd study 
vaccination) 
X (if prior to 21 days after last study 
vaccination and receipt of any non-
study influenza vaccine will be 
recorded if within 180 days after the 
2nd study) 
Vital Signs 
(Oral Temperature%, Pulse, 
and BP) 
 
 
 
 
X (may be obtained if indicated) 
X (may be obtained if indicated) 
Physical Examination3 
 
 
{X} 
 
{X} 
{X} 
Venous Blood Collection for 
Clinical Safety Laboratory 
Evaluations~ 
 
 
 
 
X (if within 7 days after the last 
study vaccination) 
X (if indicated) 
Venous Blood Collection for 
Anti-viral Antibody Assays 
 
 
X 
 
X (if within 21 days after last 
study vaccination) 
X (if prior to 21 days after last study 
vaccination) 
Serum Sample Collected for 
Future Research4 
 
 
X 
 
X(if within 21 days after last 
study vaccination 
X(if prior to 21 days after last study 
vaccination 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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26 August 2019 
Table 3:   Schedule of Study Procedures - Follow-Up Period (Including early termination and unscheduled visits) (continued) 
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Study Visit Number 
V08** 
V09** 
V10 
V11** 
Early Termination (if needed) 
Unscheduled (if needed) 
Study Day post first 
study vaccination 
D82 
D142 
D202 
D387 
Study Day post second 
study vaccination 
D61±7d 
D121±14d 
D181±14d 
D366±14d 
Study Procedure/Evaluation 
Examine Study Vaccination 
Site 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last study 
vaccination) 
Post-Administration 
Reactogenicity Assessments 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last study 
vaccination) 
Review Memory Aid 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last study 
vaccination) 
AE/SAE Assessment 
X# 
X#! 
X# 
X# 
X# 
X# 
** Phone call assessment 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study vaccination and interim medical history will be obtained 
by interview of subjects at follow-up visits after the first study vaccination. 
ς Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and reported in the eCRF. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr 
Ψ Subjects who do not receive the second study vaccination will continue with follow-up safety assessments (may be conducted by phone call) rather than in person continuing through 
approximately 12 months after their first study vaccination. These subjects will also be encouraged to provide a venous blood sample for anti-viral antibody assays at approximately 21 
and 180 days after their first study vaccination 
4 For subjects who have consented to collection of serum for future use 
* AEs will be limited to SAEs and MAAEs, including NOCMCs and PIMMCs if after 21 days after last study vaccination 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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9.7.1 Sample Size 
Table 4: 
Power (%) to Detect Safety Events  
Event 
Frequency 
N = 60 
N = 100 
N = 160 
N = 480 
≥10% 
Very Common 
>99 
>99 
>99 
>99 
≥1% 
Common 
45 
63 
80 
>99 
≥0.1% 
Uncommon 
6 
10 
15 
38 
≥0.01% 
Rare 
<1 
1 
2 
5 
 
Table 5: 
Precisions of Binomial Confidence Intervals 
N 
95% CI 
60 
37-63 
100 
40-60 
160 
42-58 
480 
45-55 
 
Table 6: 
Minimum Detectable Difference in Proportion Responders  
Assumed Proportion of subjects with titer 
≥40 in comparator arm 
19-64 years stratum  
(N = 100) 
≥65 years stratum 
(N = 50) 
0.40 
0.19 
0.27 
0.50 
0.19 
0.27 
0.60 
0.18 
0.25 
0.70 
0.16 
0.21 
0.80 
0.13 
0.16 
0.90 
0.08 
0.10 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 7: 
Lower Confidence Bound for Difference in Proportion of Responders  
Between Adjuvanted (N = 100) and Unadjuvanted (N = 50) Arms, 19-64 Years 
Stratum 
Adjuvanted Arm 
Unadjuvanted 
Arm 
Difference 
Lower Confidence 
Bound* 
0.50 
0.10 
0.40 
0.26 
0.60 
0.10 
0.50 
0.36 
0.70 
0.10 
0.60 
0.46 
0.80 
0.10 
0.70 
0.56 
0.90 
0.10 
0.80 
0.67 
* Farrington-Manning confidence limits.  
 
Table 8: 
Lower Confidence Bound for Difference in Proportion of Responders  
Between Adjuvanted (N = 50) and Unadjuvanted (N = 25) Arms, ≥65 Years Stratum 
Adjuvanted Arm 
Unadjuvanted 
Arm 
Difference 
Lower Confidence 
Bound* 
0.50 
0.10 
0.40 
0.19 
0.60 
0.10 
0.50 
0.29 
0.70 
0.10 
0.60 
0.39 
0.80 
0.10 
0.70 
0.49 
0.90 
0.10 
0.80 
0.60 
* Farrington-Manning confidence limits.  
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
10.2 
Protocol Deviations 
Table 9: 
Distribution of Protocol Deviations by Category, Type and Treatment Arm, All 
Enrolled Subjects 
Category 
Deviation Type 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg 
A/H7N9  
(N=X) 
All 
Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
Eligibility/enrollment Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Did not meet 
inclusion 
criterion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Met exclusion 
criterion 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICF not signed 
prior to study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
administration 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Out of window 
visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed 
visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed 
treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
Delayed 
treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up visit 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Out of window 
visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
Missed 
visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol 
procedure/assessment Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incorrect version 
of ICF signed 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 9: 
Distribution of Protocol Deviations by Category, Type and Treatment Arm, All 
Enrolled Subjects (continued) 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Category 
Deviation Type 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg 
A/H7N9  
(N=X) 
All 
Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
Blood not 
collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine not 
collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stool not 
collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other specimen 
not collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
Too few aliquots 
obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen result 
not obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required 
procedure not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required 
procedure done 
incorrectly 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
administration 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Required 
procedure done 
incorrectly 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Blinding 
policy/procedure 
Any type 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
unblinded 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
N= Number of subjects enrolled


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12.2.2 Displays of Adverse Events 
Table 10: 
Solicited Adverse Event Grading Scale – Local 
Local (Injection Site) Reactogenicity Grading 
Local (Injection 
Site) Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain – experienced 
without touching the 
injection site 
(spontaneous 
discomfort) 
Subject is aware of pain, 
but it does not interfere 
with daily activity, and 
no pain medication is 
taken 
Subject is aware of pain; 
there is interference with 
daily activity or it 
requires repeated use of 
a non-narcotic pain 
reliever for >24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or requires any use 
of a narcotic pain reliever 
Tenderness – hurts only 
when injection site is 
touched or the arm is 
moved 
The area immediately 
surrounding the 
injection site hurts only 
when touched or with 
arm motion, and it does 
not interfere with daily 
activity 
The area immediately 
surrounding the 
injection site hurts when 
touched or with arm 
motion, and it interferes 
with daily activity 
The area immediately 
surrounding the injection 
site hurts when touched or 
with arm motion, and it 
prevents daily activity 
Pruritus (Itching) 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Ecchymosis 
(Bruising)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Erythema (Redness)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Induration 
(Hardness)/Swelling* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Local (Injection Site) Reactogenicity Measurements 
Local (Injection Site) 
Reaction 
Small (Grade 1) 
Medium (Grade 2) 
Large (Grade 3) 
Ecchymosis 
(Bruising)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Erythema (Redness)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Induration 
(Hardness)/Swelling* 
<20 mm 
20 mm – 50 mm 
>50 mm 


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Table 11: 
Solicited Adverse Event Grading Scale - Systemic 
Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverishness 
(Chills/Shivering/Sweating) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Fatigue (Tiredness) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Malaise (General Unwell 
Feeling) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Myalgia (Body 
Aches/Muscular Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Arthralgia (Joint Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Headache 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Nausea 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Quantitative Systemic Reactogenicity Grading 
Systemic (Quantitative) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Fever# - oral† 
38.0°C – 38.4°C 
100.4°F – 101.1°F 
38.5°C – 38.9°C 
101.2°F – 102.0°F 
>38.9°C 
>102.0°F 
* Not at injection site. 
# Oral temperature assessed on Day 1 prior to the first study vaccination will be considered as baseline. A fever 
can be considered not related to the study product if an alternative etiology can be documented. 
 


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Table 12: 
Vital Signs Adverse Event Grading Scale 
For Individuals 19-64 years of age, pulse and blood pressure# will be graded as follows: 
Physiologic Parameter 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Bradycardia - beats per minute 
45 – 46 
40 – 44 
<40 
Tachycardia - beats per minute 
101 – 130 
131 – 155 
>155 
Hypotension (systolic) mmHg 
80 – 84 
75 – 79 
<75 
Hypotension (diastolic) mmHg 
50 – 54 
45 – 49 
<45 
Hypertension (systolic) mmHg 
151 – 155 
156 – 160 
>160 
Hypertension (diastolic) mmHg 
96 – 100 
101 – 105 
>105 
For Individuals >65 years of age, pulse and blood pressure# will be graded as follows: 
Physiologic Parameter 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Bradycardia - beats per minute 
45 – 46 
40 – 44 
<40 
Tachycardia - beats per minute 
101 – 130 
131 – 155 
>155 
Hypotension (systolic) mm Hg 
80 – 84 
75 – 79 
<75 
Hypotension (diastolic) mm Hg 
50 – 54 
45 – 49 
<45 
Hypertension (systolic) mm Hg 
161 – 165 
166 – 170 
>170 
Hypertension (diastolic) mm 
Hg 
96 – 100 
101 – 105 
>105 
# Pulse and blood pressure assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
 


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12.4.1 Individual Laboratory Measurements and Abnormal Laboratory Values 
Table 13: 
Laboratory Adverse Event Grading Scale 
Hematology 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC 103/µL (Decrease) 
2.5 – 3.9 
1.5 – 2.4 
<1.5 
WBC 103/µL (Increase) 
10.6 – 15.0 
15.1 – 20.0 
>20.0 
Hgb g/dL (Decrease) (Female) 
10.1 – 11.4 
8.5 – 10 
<8.5 
Hgb g/dL (Decrease) (Male) 
11.0 – 12.4 
9.5 – 10.9 
<9.5 
Platelets 103/µL (Decrease) 
125 – 139 
100 – 124 
<100 
Platelets 103/µL (Increase) 
416 – 550 
551– 750 
>750 
Chemistry 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
ALT IU/L (Increase) (Female) 
44 – 100 
101 – 200 
>200 
ALT IU/L (Increase) (Male) 
61 – 138 
139 – 275 
>275 
Total Bilirubin mg/dL (Increase) – 
when accompanied by any increase in 
ALT 
1.30 – 1.59 
1.60 – 1.80 
>1.80 
Total Bilirubin mg/dL (Increase) – 
when ALT is normal 
1.30 – 1.89 
1.90 – 2.40 
>2.40 
Creatinine mg/dL (Increase) 
(Female) 
1.1 – 1.7 
1.8 – 2.0 
>2.0 
Creatinine mg/dL (Increase) (Male) 
1.4 – 1.7 
1.8 – 2.0 
>2.0 
 
 


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14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects 
Table 14: 
Ineligibility Summary of Screen Failures* 
Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
na 
%b 
Inclusion and Exclusion 
Number of subjects failing any eligibility 
criterion 
x 
x 
Inclusion 
Any inclusion criterion 
x 
x 
 
[inclusion criterion 1] 
x 
x 
 
[inclusion criterion 2] 
x 
x 
 
[inclusion criterion 3] 
x 
x 
Exclusion 
Any exclusion criterion 
x 
x 
 
[exclusion criterion 1] 
x 
x 
 
[exclusion criterion 2] 
x 
x 
 
[exclusion criterion 3] 
x 
x 
aMore than one criterion may be marked per subject. 
bDenominator for percentages is the total number of screen failures. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 15: 
Analysis Populations by Treatment Arm, All Enrolled Subjects* 
Analysis Populations 
Reason Subjects Excluded 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Safety Population 
Any Reason 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
Modified Intent to Treat 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Post-Vaccination Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 8 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 9 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 9 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 9 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 22 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 21 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 21 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 15: Analysis Populations by Treatment Arm, All Enrolled Subjects* (continued) 
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Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 21 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 29 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 29 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 43 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 43 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
N=Number of subjects enrolled 


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Table 16: 
Analysis Populations by Treatment Arm and Age Stratum, All Enrolled Subjects* 
Analysis 
Populations 
Reason Subjects Excluded 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Safety Population 
Any Reason 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Modified Intent to 
Treat 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Post-Vaccination Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day
8 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 9 Result Reported 
by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
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Table 16: Analysis Populations by Treatment Arm and Age Stratum, All Enrolled Subjects* (continued) 
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Day 9 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day
22 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 21 Result Reported 
by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 21 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day
29 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 29 Result Reported 
by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 16: Analysis Populations by Treatment Arm and Age Stratum, All Enrolled Subjects* (continued) 
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Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day
43 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 43 Result Reported 
by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 43 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N=Number of subjects enrolled 


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Table 17: 
Subject Disposition by Treatment Arm, All Enrolled Subjects* 
Subject 
Disposition 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9 
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Screened 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
Enrolled/Randomized 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
Received Vaccination 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received Vaccination 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received All Scheduled Vaccinations a 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Blood Draw for Primary 
Immunogenicity Analysis (Day 43) 
 
 
 
 
 
 
 
 
 
 
 
 
Included in Per Protocol Primary Immunogenicity 
Analysis (Day 43)b 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Primary Follow-up (Day 43)a 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Final Study Visit (Day 387) 
 
 
 
 
 
 
 
 
 
 
 
 
N=Number of subjects enrolled 
aRefer to Listing 2 for reasons subjects discontinued from study vaccinations or terminated early. 
bRefer to Listing 5 for reasons subjects are excluded from the per protocol population. 
 


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Table 18: 
Subject Disposition by Treatment Arm and Age Stratum, All Enrolled Subjects* 
Subject 
Disposition 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Screened 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
Enrolled/Randomized 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
Received Vaccination 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received Vaccination 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received All Scheduled 
Vaccinations a 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Blood Draw for 
Primary Immunogenicity 
Analysis (Day 43) 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Included in Per Protocol 
Primary Immunogenicity 
Analysis (Day 43)b 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Primary Follow-up 
(Day 43)a 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Final Study Visit 
(Day 387) 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
N=Number of subjects enrolled 
aRefer to Listing 2 for reasons subjects discontinued from study vaccinations or terminated early. 
bRefer to Listing 5 for reasons subjects are excluded from the per protocol population. 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 19: 
Dates of First Study Vaccination by Site, Treatment Arm, and Age Stratum, for Safety Analysis Population 
Dates of Dosing 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
All 
19-64 
≥ 65 
All 
19-64 
≥ 65 
All 
19-64 
≥ 65 
All 
19-64 
≥ 65 
All 
19-64 
≥ 65 
All 
[Site 1] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Site 2] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all sites] 
N= Number of subjects in the Safety population. 
 
Table with similar format: 
Table 20: 
Dates of Second Study Vaccination by Site, Treatment Arm, and Age Stratum, for Safety Analysis Population 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1.2 Demographic Data 
Table 21: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All Enrolled Subjects 
Variable 
Characteristic 
Duke 
University 
(N=X) 
Emory  
(N=X) 
Kaiser 
Permanente 
(N=X) 
University 
of Iowa 
(N=X) 
University 
of 
Maryland 
(N=X) 
[Site 6] 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Age 
19-64 years 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
≥ 65 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific 
Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza 
Vaccination 
2016-2017 and 2017-2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2016-2017 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2017-2018 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 21: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All Enrolled Subjects (continued) 
- 61 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Characteristic 
Duke 
University 
(N=X) 
Emory  
(N=X) 
Kaiser 
Permanente 
(N=X) 
University 
of Iowa 
(N=X) 
University 
of 
Maryland 
(N=X) 
[Site 6] 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Neither 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N= Number of subjects enrolled 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 22: 
Summary of Continuous Demographic and Baseline Characteristics by Site, All Enrolled Subjects 
Variable 
Statistic 
[Site 1] 
(N=X) 
[Site 2] 
(N=X) 
[Site 3] 
(N=X) 
[Site 4] 
(N=X) 
[Site 5] 
(N=X) 
[Site 6] 
(N=X) 
All Subjects 
(N=X) 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
N= Number of subjects enrolled 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 23: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Arm, All Enrolled Subjects* 
Variable 
Characteristic 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9 
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
 
 
 
 
 
 
 
 
 
 
 
 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific 
Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza
Vaccination 
2016-2017 and 2017-2018 
 
 
2016-2017 only 
 
 
2017-2018 only 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 23: Summary of Categorical Demographic and Baseline Characteristics by Treatment Arm, All Enrolled Subjects (continued) 
- 64 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Characteristic 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9 
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Neither 
 
 
Unknown 
 
 
N=Number of subjects enrolled 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 24: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Arm and Age Stratum, All Enrolled 
Subjects* 
Variable 
Characteristic 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or 
Alaska Native 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other 
Pacific Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African 
American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal 
Influenza 
Vaccination 
2016-2017 and 2017-2018 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 24: Summary of Categorical Demographic and Baseline Characteristics by Treatment Arm and Age Stratum, All Enrolled 
Subjects (continued) 
- 66 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Characteristic 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
2016-2017 only 
 
 
2017-2018 only 
 
 
Neither 
 
 
Unknown 
 
 
N=Number of subjects enrolled 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 25: 
Summary of Continuous Baseline Characteristics by Treatment Arm, All Enrolled Subjects* 
Variable 
Statistic 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
N=Number of subjects enrolled. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 26: 
Summary of Continuous Baseline Characteristics by Treatment Arm and Age Stratum, All Enrolled Subjects* 
 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
Variable 
Statistic 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N=Number of subjects enrolled 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1.3 Summary of Prior or Concurrent Medical Conditions 
Table 27: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA System Organ Class and Treatment Arm, 
Safety Analysis Population 
MedDRA System Organ Class 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety population;  
n = Number of subjects reporting medical history within the specified SOC. A subject is only counted once per SOC. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 28: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA System Organ Class, Treatment Arm and 
Age Stratum, Safety Analysis Population 
MedDRA System Organ 
Class 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety population;  
n = Number of subjects reporting medical history within the specified SOC. A subject is only counted once per SOC. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 71 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.2 
Immunogenicity Tables 
14.2.1 Immune Response Against 2017 A/H7N9 
Table 29: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Arm, Modified 
Intent-to-Treat Population*†‡ 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Day 1 (Pre-Vaccination 1) 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 1 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Vaccination 1 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 2 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 29: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Arm, Modified 
Intent-to-Treat Population (continued) 
- 72 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Vaccination 2 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
180 Days Post Vaccination 2 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
Tables with similar format 
Table 30: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Arm, Per Protocol 
Population*‡ 
Table 31: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and Treatment Arm, Modified Intent-to-Treat 
Population*†‡ 
Table 32: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and Treatment Arm, Per Protocol Population*‡ 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 73 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 33: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, 
Modified Intent-to-Treat Population*†‡ 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Day 1 (Pre Vaccination 1) 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 1 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Vaccination 1 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 2 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 33: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, 
Modified Intent-to-Treat Population (continued) 
- 74 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Vaccination 2 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
180 Days Post Vaccination 
2 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 33: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, 
Modified Intent-to-Treat Population (continued) 
- 75 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Seroconversion - % (95% 
CI)b  
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
 
Tables with similar format 
Table 34: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, 
Per Protocol Population*‡ 
Table 35: Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified Intent-
to-Treat Population*†‡ 
Table 36: Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population*‡ 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 76 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 37: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm and Age Categories at 21 Days 
Post Second Vaccination, Per-Protocol Population* 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Age 19-34 years 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age 35-49 years 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age 50-64 years 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
 
 
 
 
 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age 65-80 years 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 37: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm and Age Categories at 21 Days 
Post Second Vaccination, Per-Protocol Population (continued) 
- 77 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age ≥ 81 years 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x (xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold 
Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 78 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 38: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm and Age Stratum at 180 Days 
Post Second Vaccination, Per-Protocol Population* 
Table 39: Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm and Age Stratum at 21 Days Post Second 
Vaccination, Per-Protocol Population* 
Table 40: Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm and Age Stratum at 180 Days Post Second 
Vaccination, Per-Protocol Population* 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 79 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 41: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Sex at 21 
Days Post Second Vaccination, Per-Protocol Population* 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Female 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Male 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold 
Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
Tables with similar format: 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 41: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Sex at 21 
Days Post Second Vaccination, Per-Protocol Population (continued) 
- 80 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 42: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Sex at 180 
Days Post Second Vaccination, Per-Protocol Population* 
Table 43: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Sex at 21 Days Post Second 
Vaccination, Per-Protocol Population* 
Table 44: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Sex at 180 Days Post Second 
Vaccination, Per-Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 81 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 45: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and BMI at 21 
Days Post Second Vaccination, Per-Protocol Population* 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
BMI < 30 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT 
(95% 
CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % 
(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR 
(95% 
CI)a 
xxx.x 
(xxx.x,xxx.x) 
 
 
 
 
 
 
 
 
 
Seroconversion 
- % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
BMI ≥ 30 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT 
(95% 
CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
 
Titer ≥ 1:40 - % 
(95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 
GMFR 
(95% 
CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion 
- % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold 
Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 45: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and BMI at 21 
Days Post Second Vaccination, Per-Protocol Population (continued) 
- 82 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 46: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and BMI at 180 
Days Post Second Vaccination, Per-Protocol Population* 
Table 47: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and BMI at 21 Days Post Second 
Vaccination, Per-Protocol Population* 
Table 48: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and BMI at 180 Days Post Second 
Vaccination, Per-Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 83 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 49: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Prior 
Seasonal Influenza Vaccination at 21 Days Post Second Vaccination, Per-Protocol Population* 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Did Not Receive 2016-2017 
or 2017-2018 Seasonal 
Influenza Vaccination 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Received 2016-2017 and/or 
2017-2018 Seasonal 
Influenza Vaccination 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% 
CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 84 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 50: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Prior 
Seasonal Influenza Vaccination at 180 Days Post Second Vaccination, Per-Protocol Population* 
Table 51: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Prior Seasonal Influenza 
Vaccination at 21 Days Post Second Vaccination, Per-Protocol Population* 
Table 52: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Arm, Age Stratum and Prior Seasonal Influenza 
Vaccination at 180 Days Post Second Vaccination, Per-Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 85 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 53: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with HAI Seroconversion 
Against 2017 A/H7N9 at 21 Days Post Second Study Vaccination, Per Protocol Population* 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Treatment 
 3.75 
mcg 
with 
AS03 
Adjuvant 
(reference) 
- 
- 
- 
- 
- 
 7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age 
 19-64 years (reference) 
- 
- 
- 
- 
- 
 ≥65 years 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 Adjuvant 
- 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*3.75 mcg with AS03 adjuvant 
- 
- 
- 
- 
- 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis. 
P-value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX.  
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 86 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 54: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Neut Seroconversion 
Against 2017 A/H7N9 at 21 Days Post Second Study Vaccination, Per Protocol Population* 
Table 55: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with HAI Seroconversion 
Against 2017 A/H7N9 at 180 Days Post Second Study Vaccination, Per Protocol Population* 
Table 56: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Neut Seroconversion 
Against 2017 A/H7N9 at 180 Days Post Second Study Vaccination, Per Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 87 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 57: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with HAI Seroconversion 
Against 2017 A/H7N9 at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
- 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
 3.75 
mcg 
with 
AS03 
Adjuvant 
(reference) 
- 
- 
- 
- 
- 
 7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age 
 19-64 years (reference) 
- 
- 
- 
- 
- 
 ≥65 years 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 Adjuvant 
- 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Sex 
 Female (reference) 
- 
- 
- 
- 
- 
 Male 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
BMI Category 
 <30 (reference) 
- 
- 
- 
- 
- 
 ≥30 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Prior Receipt of Influenza Vaccine 
 Did Not Receive 2016-2017 or 2017-
2018 
Seasonal 
Influenza 
Vaccine 
(reference) 
- 
- 
- 
- 
- 
 Received 2016-2017 or 2017-2018 
Seasonal Influenza Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis. P-
value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 88 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 58: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Neut Seroconversion 
Against 2017 A/H7N9 at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Table 59: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with HAI Seroconversion 
Against 2017 A/H7N9 at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* 
Table 60: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Neut Seroconversion 
Against 2017 A/H7N9 at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population* 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 89 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 61: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
HAI Titer at 21 Days Post Second Study Vaccination, Per Protocol Population* 
Model Parameter 
Parameter Levels 
 
Parameter 
Estimate 
SE 
95%CI 
p-value 
Intercept 
 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
 3.75 mcg with AS03 adjuvant (reference) 
- 
- 
- 
- 
 7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age 
 19-64 years (reference) 
- 
- 
- 
- 
 ≥65 years 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 adjuvant 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis. P-
value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 90 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 62: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
Neut Titer at 21 Days Post Second Study Vaccination, Per Protocol Population* 
Table 63: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
HAI Titer at 180 Days Post Second Study Vaccination, Per Protocol Population* 
Table 64: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
Neut Titer at 180 Days Post Second Study Vaccination, Per Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 91 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 65: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
HAI Titer at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Model Parameter 
Parameter Levels 
 
Parameter 
Estimate 
SE 
95%CI 
p-value 
Intercept 
- 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
 3.75 mcg with AS03 adjuvant (reference) 
- 
- 
- 
- 
 7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age 
 19-64 (reference) 
- 
- 
- 
- 
 ≥65 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 adjuvant 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
 
 
 
 
Sex 
 Female (reference) 
- 
- 
- 
- 
 Male 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
BMI Category 
 <30 (reference) 
- 
- 
- 
- 
 ≥30 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Prior Receipt of Influenza Vaccine 
Did Not Receive 2016-2017 or 2017-2018 
Seasonal Influenza Vaccine (reference) 
- 
- 
- 
- 
 Received 2016-2017 or 2017-2018 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population.. XX subjects missing covariate data were excluded from this analysis.  
P-value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 
Tables with similar format: 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
- 92 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Table 66: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
Neut Titer at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Table 67: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
HAI Titer at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Table 68: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
Neut Titer at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with HAI Seroconversion 
Against 2017 A/H7N9 at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates and Age in Years, Per 
Protocol Population* 
Model Parameter 
Parameter Levels 
 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
- 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
 3.75 
mcg 
with 
AS03 
adjuvant 
(reference) 
- 
- 
- 
- 
- 
 7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
 15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age (years) 
- 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 adjuvant 
- 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   Age*15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
   Age*45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Sex 
 Female (reference) 
- 
- 
- 
- 
- 
 Male 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
BMI Category 
 <30 (reference) 
- 
- 
- 
- 
- 
 ≥30 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Prior Receipt of Influenza Vaccine 
 Did Not Receive 2016-2017 or 2017-
2018 
Seasonal 
Influenza 
Vaccine 
(reference) 
- 
- 
- 
- 
- 
 Received 2016-2017 or 2017-2018 
Seasonal Influenza Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population.. XX subjects missing covariate data were excluded from this analysis. P-
value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 70: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and AS03 Adjuvant with Log-Adjusted 
HAI Titer at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates and Age in Years, Per Protocol 
Population* 
Model Parameter 
Parameter Levels 
 
Parameter Estimate 
SE 
95%CI 
p-value 
Intercept 
- 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
 3.75 mcg with AS03 Adjuvant (reference) 
- 
- 
- 
- 
 7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age (years) 
- 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Interaction: Age*Treatment 
   Age*3.75 mcg with AS03 Adjuvant 
- 
- 
- 
- 
   Age*7.5 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg with AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*15 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
   Age*45 mcg without AS03 Adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Sex 
 Female (reference) 
- 
- 
- 
- 
 Male 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
BMI Category 
 <30 (reference) 
- 
- 
- 
- 
 ≥30 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Prior Receipt of Influenza
Vaccine 
 Did Not Receive 2016-2017 or 2017-2018 
Seasonal Influenza Vaccine (reference) 
- 
- 
- 
- 
 Received 2016-2017 or 2017-2018 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
N = XX subjects with results available at 21 days post second vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis.  
P-value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 71: 
Summaries of Hemagglutination Inhibition Antibody Against Antigenically Drifted Variants by Study Day, Treatment Arm 
and Age Stratum, Per Protocol Population* 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
Strain = [Antigenically Drifted Variant] 
Day 1 (Pre Vaccination 1) 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Day 21 Post Vaccination 2 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Day 180 Post Vaccination 2 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Titer ≥ 1:40 - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
GMFR (95% CI)a 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
xxx.x 
(xxx.x,xxx.x) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
[repeat for each antigenically drifted variant of the A/H7 virus] 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 71:  Summaries of Hemagglutination Inhibition Antibody Against Antigenically Drifted Variants by Study Day, Treatment Arm 
and Age Stratum, Per Protocol Population (continued) 
- 96 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer; GMFR = Geometric Mean Fold Rise 
a Confidence Interval calculated based on the student’s T distribution. 
b Exact binomial confidence interval calculated using the Clopper-Pearson methodology. 
 
Table with similar format: 
Table 72: 
Summaries of Neutralizing Antibody Against Antigenically Drifted Variants by Study Day, Treatment Arm and Age Stratum, 
Per Protocol Population* 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 73: 
Overall Summary of Adverse Events  - Safety Population*‡ 
 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg 
A/H7N9  
(N=X) 
All Subjects  
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one local solicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one systemic solicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one related unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Mild (Grade 1) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Moderate (Grade 2)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Severe (Grade 3)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Not yet assessed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one severe (Grade 3) unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Related  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Unrelated 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Not yet assessed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one serious adverse eventb 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one related, serious adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 73: Overall Summary of Adverse Events  – Safety Population * (continued) 
- 98 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg 
A/H7N9  
(N=X) 
Group 5 
45 mcg 
A/H7N9  
(N=X) 
All Subjects  
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one adverse event leading to early terminationc  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one medically attended adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one new onset chronic medical condition 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one potentially immune mediated medical condition 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N = Number of subjects who received at least one study vaccination 
a Subjects are counted once for each category regardless of the number of events. 
b A listing of Serious Adverse Events is included in Table 99 
c As reported on the Adverse Event eCRF 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 74: 
Number of Adverse Events Occurring in 5% of Subjects in Any Treatment Group by MedDRA System Organ Class and 
Preferred Term, and Treatment Group - Safety Population 
Preferred Term 
MedDRA System 
Organ Class 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9 
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
All Subjects  
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% Events n 
% Events
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (Non-serious) Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects in the safety population (number of subjects at risk). n= number of subjects reporting event. Events = total frequency of events reported. 
MedDRA Version X.X. 
The preferred term “Pain injection site” identifies both injection site tenderness and injection site pain. To distinguish between the two events, the preferred term “Pain injection
site (tenderness)” was used to identify injection site tenderness. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 100 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.1.1 
Solicited Adverse Events 
Table 75: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Arm Post Any Study Vaccination – Safety Population* 
Symptom 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
Any Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Local Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 75: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Arm– Post Any Study Vaccination – Safety Population (continued) 
- 101 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Induration/Swelling 
(measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
N = Number of subjects in the Safety Population who received any study vaccination. 
95% CI estimated using Clopper-Pearson exact method 
 
Tables with similar format: 
Table 76: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Arm Post Study Vaccination 1 – Safety Population * 
[Footnote update] N = Number of subjects in the Safety Population who received the first vaccination. 
 
Table 77: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Arm Post Study Vaccination 2 – Safety Population * 
[Footnote update] N = Number of subjects in the Safety Population who received the second vaccination. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 102 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 78: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, 
Treatment Arm and Age Stratum Post Any Study Vaccination – Safety Population * 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
 Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Symptom 
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
Age 19-64 
Any Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Local Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 78: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Treatment 
Arm and Age Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 103 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
 Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Symptom 
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
Induration/Swelling 
(measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Age 65+ 
Any Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Local Symptom 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema (measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 78: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Treatment 
Arm and Age Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 104 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
 Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
Symptom 
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
n 
%  
95% 
CI  
Induration/Swelling 
(measurement) 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
N = Number of subjects in the Safety Population who received any study vaccination. 
95% CI estimated using Clopper-Pearson exact method 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 105 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 79: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Treatment 
Arm and Age Stratum Post Study Vaccination 1 – Safety Population * 
[Footnote update] N = Number of subjects in the Safety Population who received the first vaccination. 
 
Table 80: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Treatment 
Arm and Age Stratum Post Study Vaccination 2 – Safety Population * 
[Footnote update] N = Number of subjects in the Safety Population who received the second vaccination. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 106 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 81: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose, AS03 Adjuvant, and Age with Reporting Any 
Local Event Post Any Study Vaccination – Safety Population * 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
- 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
 3.75 mcg with AS03 adjuvant (reference) 
- 
- 
- 
- 
- 
 7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age 
 19-64 years (reference) 
- 
- 
- 
- 
- 
 ≥65 years 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Interaction  
(Age * Treatment) 
   ≥65 years * 7.5 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   ≥65 years * 15 mcg with AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   ≥65 years * 15 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
   ≥65 years * 45 mcg without AS03 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = XX subjects in the safety population. 
P-value for Treatment = 0.XXX; P-value for Age = 0.XXX; P-value for interaction of Treatment and Age = 0.XXX. 
 
Table with similar format: 
 
Table 82: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose, AS03 Adjuvant, and Age with Reporting Any 
Systemic Event Post Any Study Vaccination (N=X) – Safety Population * 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 107 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 83: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and 
Treatment Arm Post Any Study Vaccination – Safety Population * 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
Any Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic 
Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 83: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm – 
Post Any Study Vaccination – Safety Population (continued) 
- 108 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Local Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 83: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm – 
Post Any Study Vaccination – Safety Population (continued) 
- 109 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 83: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm – 
Post Any Study Vaccination – Safety Population (continued) 
- 110 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
Erythema 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
N = Number of subjects in the Safety Population who received any study vaccination. 
95% CI estimated using Clopper-Pearson exact method 
Severity is the maximum severity reported over all solicited symptoms post dosing for each subject.  


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 111 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 84: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm Post 
Study Vaccination 1 – Safety Population * 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the first study vaccination. 
 
Table 85: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm Post 
Study Vaccination 2 – Safety Population * 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the second study vaccination. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 112 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 86: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, 
Treatment Arm and Age Stratum Post Any Study Vaccination – Safety Population * 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
Age 19-64 
Any Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic 
Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 113 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 114 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
Any Local 
Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 115 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
Ecchymosis 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 116 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Age 65+ 
Any Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Systemic 
Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fever 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Feverishness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Fatigue 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 117 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Malaise 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Myalgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Arthralgia 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Headache 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Nausea 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 118 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Any Local 
Symptom 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pain 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Tenderness 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Pruritus 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 119 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Ecchymosis 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Erythema 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
Induration/Swelling 
(measurement) 
None 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 86: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 120 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
95% CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
N = Number of subjects in the Safety Population who received any study vaccination. 
95% CI estimated using Clopper-Pearson exact method 
Severity is the maximum severity reported over all solicited symptoms post dosing for each subject. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 121 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 87: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum Post Study Vaccination 1 – Safety Population * 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the first study vaccination. 
 
Table 88: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Treatment Arm and Age 
Stratum Post Study Vaccination 2 – Safety Population * 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the second study vaccination. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
Version 2.0 
 
26 August 2019 
- 122 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 89: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum Post Any Study Vaccination – Safety Population 
Symptom 
Severity 
Pre-Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: 3.75 mcg A/H7N9 + AS03 (N=X) 
All Subjects 
Any Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Systemic Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malaise 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 89: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 123 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 89: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 124 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tenderness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pruritus 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ecchymosis 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ecchymosis (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 89: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum – Post Any Study Vaccination – Safety Population (continued) 
- 125 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for Ages 19-64 and  ≥ 65] 
[repeat for all treatment arms] 
N = Number of subjects in the Safety Analysis Population who received any study vaccination.  
Severity is the maximum severity reported post dosing for each subject for each day. 


Statistical Analysis Plan - DMID Protocol: 17-0075 
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Tables with similar format: 
Table 90: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum Post Study Vaccination 1 – Safety Population 
Footnote update: N = Number of subjects in the Safety Analysis Population who received the first study vaccination. 
Table 91: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, 
Treatment Arm and Age Stratum Post Study Vaccination 2 – Safety Population 
Footnote update: N = Number of subjects in the Safety Analysis Population who received the second study vaccination. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
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Table 92: 
Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 1 Compared with Dose 2 
by Treatment Arm and Age Stratum – Safety Population 
Treatment 
Arm 
Age Stratum 
Study Vaccination 1 
Study Vaccination 2 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
Group 1  
3.75 mcg 
A/H7N9 + 
AS03 
Ages 19-64 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages ≥ 65 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
All Subjects 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Group 2  
7.5 mcg 
A/H7N9 + 
AS03 
Ages 19-64 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages ≥ 65 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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26 August 2019 
Table 92: Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 1 Compared with Dose 2 by Treatment 
Arm and Age Stratum – Safety Population (continued) 
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Treatment 
Arm 
Age Stratum 
Study Vaccination 1 
Study Vaccination 2 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
All Subjects 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Group 3  
15 mcg 
A/H7N9 + 
AS03 
Ages 19-64 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages ≥ 65 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
All Subjects 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages 19-64 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 92: Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 1 Compared with Dose 2 by Treatment 
Arm and Age Stratum – Safety Population (continued) 
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Treatment 
Arm 
Age Stratum 
Study Vaccination 1 
Study Vaccination 2 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
Group 4 
15 mcg 
A/H7N9 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages ≥ 65 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
All Subjects 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Group 5  
45 mcg 
A/H7N9 
Ages 19-64 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Ages ≥ 65 
Subjects with No 
Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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26 August 2019 
Table 92: Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 1 Compared with Dose 2 by Treatment 
Arm and Age Stratum – Safety Population (continued) 
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Treatment 
Arm 
Age Stratum 
Study Vaccination 1 
Study Vaccination 2 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
All Subjects 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or 
Greater Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Note: Denominators for percentages are the number of subjects in the safety population who received both the first and second study vaccination. [x] subjects 
did not get the second dose and are not included in this table. 
* P-value is calculated from McNemar's test for each group and age stratum pair. 
 
Table with similar format:  
Table 93: 
Number and Percentage of Subjects Experiencing Solicited Local Events for Dose 1 Compared with Dose 2 by Treatment 
Arm and Age Stratum – Safety Population 
 


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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.1.2 
Unsolicited Adverse Events 
Table 94: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA System Organ Class and Preferred Term, and Treatment Arm – Safety Population * 
 
 
Group 1 
3.75 mcg 
A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
Any SOC 
Any PT 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
Note: N = number of subjects in the Safety Analysis Population who received any study vaccination. This table presents number and percentage of subjects. A subject is only counted 
once per PT. 
 


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Table 95: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA System Organ Class and Preferred Term, Treatment Arm and Age Stratum – Safety Population * 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64  
≥ 65 
19-64  
≥ 65 
19-64  
≥ 65 
19-64  
≥ 65 
19-64  
≥ 65 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
Any SOC 
Any PT 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
x 
xx  
(xx-
xx) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = number of subjects in the Safety Analysis Population who received any study vaccination. This table presents number and percentage of subjects. A subject is only counted 
once per PT. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 96: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA System Organ Class and 
Preferred Term, Maximum Severity, Relationship, Treatment Arm and Age Stratum – Safety Population* 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severity [1] 
Relationship to Treatment [2] 
Mild 
Moderate 
Severe 
Not Related 
Related 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1 3.75 mcg A/H7N9 + AS03 (N = X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for Ages 19-64 and ≥ 65] 
[Repeat for all treatment arms] 
Note: N = Number of subjects in the Safety Analysis Population.  
[1] For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
[2] For relationship, a subject is only counted once per preferred term and is summarized according to their closest relationship. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 97: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited Adverse Events by MedDRA System 
Organ Class and Preferred Term, Maximum Severity, Treatment Arm and Age Stratum – Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severity [1] 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1 3.75 mcg A/H7N9 + AS03 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
[Repeat for Ages 19-64 and ≥ 65] 
[Repeat for all treatment arms] 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects.  
[1] For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 98: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 21 Days Post Study Vaccination by 
MedDRA System Organ Class and Preferred Term, Day Post Vaccination, Treatment Arm and Age Stratum – Safety 
Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22  
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1 3.75 mcg A/H7N9 + AS03, (N=X) 
All Subjects  
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for Ages 19-64 and ≥ 65 ] 
[Repeat for all treatment arms] 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects. For each time period, a subject is only counted once per 
PT. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 99: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited Adverse Events Within 21 Days Post 
Vaccination by MedDRA System Organ Class and Preferred Term, Study Vaccination, Treatment Arm and Age Stratum – 
Safety Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22 
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1 3.75 mcg A/H7N9 + AS03 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for Ages 19-64 and ≥ 65] 
[Repeat for all treatment arms] 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects. For each time period, a subject is only counted once per 
PT. 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 100: Number of Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Day Post Vaccination, 
Treatment Arm and Age Stratum – Safety Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22 
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred Term 
# of Events 
# of 
Events 
# of Events 
# of Events 
# of Events 
# of Events 
# of Events 
Group 1 3.75 mcg A/H7N9 + AS03 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
x 
x 
x 
x 
x 
x 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
[Repeat for Ages 19-64 and ≥ 65] 
[Repeat for all treatment arms] 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number of events; a subject may be counted multiple times. 
 


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14.3.2 Listings of Serious and Significant Adverse Events 
Table 101: Listing of Serious Adverse Events – Safety Population * 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. If the event is ongoing (no stop 
date), indicate “ongoing” in the “Duration” column. If more than one reason is selected for the reason reported as an SAE, list all reasons in the 
column, separated by a comma. In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate etiology, separate 
by a colon. In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-identification.] 
Adverse 
Event 
Associated 
with Vac # 
# of Days 
Post 
Associated 
Dose 
(Duration) 
# of 
Days 
Post 
Vac the 
Event 
Became 
Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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Table 102: Listing of Adverse Events of Special Interest – Safety Population * 
[Implementation Note: This listing is included in the tables section, as it is included in the body of the CSR. If the event is ongoing (no stop date), 
indicate “ongoing” in the “Duration” column. In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate 
etiology, separate by a colon.] 
Adverse 
Event 
Associated 
with Vac # 
# of Days 
Post 
Associated 
Vac 
(Duration) 
SAE? 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken 
with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MAAE 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
SAE: No 
Mild 
 
 
 
 
 
 
 
 
Comments: 
 
 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Tables with similar format: 
Table 103: Listing of New Onset Chronic Medical Conditions – Safety Population * 
Table 104: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Safety Population * 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
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14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events  
(not included in SAP, but this is a placeholder for the CSR) 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.4 Displays of Laboratory Results 
Table 105: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, 
All Laboratory Parameters – Safety Population * 
Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild/ 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1  
3.75 mcg 
A/H7N9 + 
AS03 
Ages 19-64 
Baseline 
x 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ages ≥ 65 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
All 
Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all 
Treatment 
Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 105: 
 Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, All Laboratory 
Parameters – Safety Population * (continued) 
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Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild/ 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments. N* is the denominator for calculating percentages. 
N=Number of subjects in the Safety population; N*=Number of subjects who completed the indicated visit. 
 
 
Tables with similar format:  
Table 106: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, Hemoglobin – Safety 
Population * 
Table 107: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, Alanine – Safety 
Population aminotransferase (ALT)* 
Table 108: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, Total Bilirubin – 
Safety Population * 
Table 109: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Group and Age Stratum, Creatinine – Safety 
Population * 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075 
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Table 110: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Arm and Age Stratum, White Blood Cells – 
Safety Population * 
Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild/ 
Grade 1 
(Low) 
Mild/ 
Grade 1 
(High) 
Moderate/ 
Grade 2 
(Low) 
Moderate/ 
Grade 2 
(High) 
Severe/ 
Grade 3 
(Low) 
Severe/ 
Grade 3 
(High) 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1  
3.75 mcg 
A/H7N9 + 
AS03 
Ages 19-
64 
Baseline 
x 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max 
Severity 
Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ages ≥ 65 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max 
Severity 
Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All 
Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0075  
Version 2.0 
26 August 2019 
Table 110: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Arm and Age Stratum – White Blood Cells – 
Safety Population (continued) 
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Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild/ 
Grade 1 
(Low) 
Mild/ 
Grade 1 
(High) 
Moderate/ 
Grade 2 
(Low) 
Moderate/ 
Grade 2 
(High) 
Severe/ 
Grade 3 
(Low) 
Severe/ 
Grade 3 
(High) 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
Max 
Severity 
Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all 
Treatment 
Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments. N* is the denominator for calculating percentages. 
N=Number of subjects in the Safety population; N*=Number of subjects who completed the indicated visit. 
 
Table with similar format: 
 
Table 111: Laboratory Results by Parameter, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Platelets – Safety 
Population * 
 


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Table 112: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, White Blood Cells – Safety 
Population * 
Treatment Group 
Age Stratum 
Study Day 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
Group 1  
3.75 mcg A/H7N9 + AS03 
Ages 19-64 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
 
 
Day 8 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
Ages ≥ 65 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
[Repeat for all Treatment 
Arms] 
 
 
 
 
 
 
 
N= Number of subjects in the Safety population 
Tables with similar format: 
Table 113: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, Hemoglobin – Safety 
Population * 
Table 114: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, Platelets – Safety Population * 
Table 115: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, Alanine Aminotransferase – 
Safety Population * (ALT) 
Table 116: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, Total Bilirubin – Safety 
Population * 


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Table 117: Laboratory Summary Statistics by Parameter, Study Day, Treatment Arm and Age Stratum, Creatinine – Safety  
Population * 
Table 118: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum, White 
Blood Cells – Safety Population * 
Table 119: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum, 
Hemoglobin – Safety Population * 
Table 120: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum, 
Platelets – Safety Population * 
Table 121: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum, 
Alanine aminotransferase (ALT) – Safety Population * 
Table 122: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum,  
Total Bilirubin – Safety Population * 
Table 123: Laboratory Summary Statistics of Change from Baseline by Parameter, Study Day, Treatment Arm and Age Stratum, 
Creatinine – Safety Population * 
 
 


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14.3.4.5 
Clinical Laboratory Reference Ranges 
(Placeholder for the CSR) 
 


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14.3.5 Abnormal Laboratory Value Listings (by Subject) 
Table 124: Listing of Abnormal Laboratory Results - Chemistry  
Subject 
ID 
Treatment 
Arm 
Age 
Stratum 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 125: Listing of Abnormal Laboratory Results - Hematology 
Subject 
ID 
Treatment 
Arm 
Age 
Stratum 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken 
with Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.3.6 Displays of Vital Signs 
Table 126: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Any Assessment – Safety 
Population * 
Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild 
Moderate 
Severe 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1  
3.75 mcg A/H7N9 
+ AS03 
Ages 19-64 
Baseline 
x 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ages ≥ 65 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all 
Treatment Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments. N* is the denominator for calculating percentages. 
N=Number of subjects in the Safety population; N*=Number of subjects who completed the indicated visit. 
 
Table with similar format: 
Table 127: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Oral Temperature – Safety 
Population 


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Table 128: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Systolic Blood Pressure – 
Safety Population 
Treatment 
Group 
Age 
Stratum 
Study Day 
N 
N* 
None 
Mild 
(Low) 
Mild 
(High) 
Moderate 
(Low) 
Moderate 
(High) 
Severe 
(Low) 
Severe 
(High) 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1  
3.75 mcg 
A/H7N9 + 
AS03 
Ages 19-64 
Baseline 
x 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ages ≥ 65 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for 
all 
Treatment 
Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments. N* is the denominator for calculating percentages. 
N=Number of subjects in the Safety population; N*=Number of subjects who completed the indicated visit. 
 
 
 


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Tables with similar format: 
Table 129: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Diastolic Blood Pressure – 
Safety Population 
Table 130: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Arm and Age Stratum, Pulse – Safety Population 
 


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14.4 
Summary of Concomitant Medications 
Table 131: Number and Percentage of Subjects with Prior and Concurrent Medications by WHO Drug Classification 
and Treatment Arm – Safety Population 
WHO Drug Code 
Level 1, Anatomic Group 
WHO Drug Code 
Level 2, Therapeutic 
Subgroup 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Level 1 Codes 
Any Level 2 Codes 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[ATC Level 1 - 1] 
Any [ATC 1 – 1] 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
[ATC Level 1 – 2] 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
N= Number of subjects in the Safety population. n=Number of subjects reporting taking at least one medication in the specific WHO Drug Class. 
 
 


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Table 132: Number and Percentage of Subjects with Prior and Concurrent Medications by WHO Drug Classification, Treatment Arm 
and Age Stratum – Safety Population 
WHO Drug Code 
Level 1, Anatomic 
Group 
WHO Drug Code 
Level 2, 
Therapeutic 
Subgroup 
Group 1 
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
Group 2 
7.5 mcg A/H7N9  
+ AS03 
(N=X) 
Group 3 
15 mcg A/H7N9  
+ AS03 
(N=X) 
Group 4 
15 mcg A/H7N9  
(N=X) 
Group 5 
45 mcg A/H7N9  
(N=X) 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
19-64 
≥ 65 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any Level 1 Codes 
Any Level 2 Codes 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[ATC Level 1 - 1] 
Any [ATC 1 – 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC Level 1 – 2] 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N= Number of subjects in the Safety population. n=Number of subjects reporting taking at least one medication in the specific WHO Drug Class. 
 


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APPENDIX 2. FIGURE MOCK-UPS 
LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram* ........................................................................................ 157 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified Intent 
to Treat Population* .................................................................................................... 158 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population* ................................................................................................................. 158 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 2017 A/H7N9 by 
Study Day, Treatment Arm and Age Stratum, Modified Intent to Treat Population* 158 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against 2017 A/H7N9 by 
Study Day, Treatment Arm and Age Stratum, Per Protocol Population* ................... 158 
Figure 6: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 2017 
A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified Intent to Treat 
Population* ................................................................................................................. 159 
Figure 7: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/H5N8 by 
Study Day, Treatment Arm and Age Stratum, Per Protocol Population* ................... 159 
Figure 8: 
Geometric Mean Titers of Neutralizing Antibody against A/H5N8 Study Day, 
Treatment Arm and Age Stratum, Modified Intent to Treat Population* ................... 159 
Figure 9: 
Geometric Mean Titers of Neutralizing Antibody against A/H5N8 by Study Day, 
Treatment Arm and Age Stratum, Per Protocol Population* ...................................... 159 
Figure 10: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified 
Intent-to-Treat Population* ......................................................................................... 160 
Figure 11: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population* ................................................................................................................. 160 
Figure 12: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population* ................................................................................................... 161 
Figure 13: 
Reverse Cumulative Distribution of Neutralizing Antibody against [Antigenically 
Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population ................................................................................................................... 161 
Figure 14: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population ..................................................................................................... 162 
Figure 15: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population ..................................................................................................... 162 
Figure 16: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against [Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, 
Per Protocol Population ............................................................................................... 163 
Figure 17: 
Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population ..................................................................................................... 163 
Figure 18: 
Correlation of Neutralizing Antibody Against 2017 A/H7N9 and [Antigenically Drifted 
Strain] by Study Day, Treatment Arm and Age Stratum, Per Protocol Population .... 163 


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Figure 19: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Study 
Vaccination ................................................................................................................. 164 
Figure 20: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post Study 
Vaccination ................................................................................................................. 164 
Figure 21: 
Frequency of Unsolicited Adverse Events by MedDRA System Organ Class and 
Severity ....................................................................................................................... 165 
Figure 22: 
Incidence of Unsolicited Adverse Events by MedDRA System Organ Class and 
Severity ....................................................................................................................... 166 
Figure 23: 
Frequency of Adverse Events by MedDRA System Organ Class and Relationship to 
Treatment .................................................................................................................... 167 
Figure 24: 
Incidence of Adverse Events by MedDRA System Organ Class and Relationship to 
Treatment .................................................................................................................... 168 
Figure 25: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Laboratory 
Parameter and Treatment Arm – White Blood Cells .................................................. 169 
Figure 26: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Arm – Hemoglobin ........................................... 169 
Figure 27: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Platelets ................................ 169 
Figure 28: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Arm – Alanine Aminotransferase (ALT) .......... 169 
Figure 29: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Total Bilirubin ...................... 170 
Figure 30: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Creatinine ............................. 170 
 
 


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10.1 
Disposition of Subjects Figures 
Figure 1: 
CONSORT Flow Diagram* 
 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Assessed for Eligibility (n=x) 
Excluded* (n=x) 
♦ [Reason 1] (n=x) 
♦ Concern of potential risk (n=x) 
Randomized (n=x) 
Allocation 
Analysis 
Follow-Up 
Enrollment 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 


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14.2.2 Immunogenicity Figures 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified 
Intent to Treat Population* 
[Implementation Note: A generic sample figure is shown below. The RCD curves should be presented 
in a single figure with separate panels for each study day (, Day 8, Day 22, Day 29, Day 43, Day 202). 
Figures generated for expedited interim analysis and preliminary report will include data from all 
available visits at the time of report generation. Visit labels should be included in the panel headers. 
Within each panel individual curves should be used for each treatment arm and strata within treatment 
arm (ten curves). Each treatment arm should have a separate color and marker with dashed/solid lines 
used to distinguish strata (19-65, ≥65).] 
 
 
 
Figures with similar format: 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population* 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 2017 A/H7N9 by 
Study Day, Treatment Arm and Age Stratum, Modified Intent to Treat Population* 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against 2017 A/H7N9 by 
Study Day, Treatment Arm and Age Stratum, Per Protocol Population* 
 


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Figure 6: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 2017 
A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified Intent to Treat 
Population* 
[Implementation Note: A generic sample figure is shown below. Planned Study Day is plotted along the 
x-axis, with visit labels as tick labels. Titer is plotted on the y-axis on the log-10 scale. GMT should be 
plotted at each visit with upper and lower error bars for the 95% CI for each treatment group with 
different marker shapes/colors for each treatment arm. Each treatment arm should have a separate color 
and marker shape, with open/closed markers and dashed/solid lines used to distinguish strata (19-65, 
≥65)] 
 
Note: this figure will be generated for the preliminary report including data through Day 43, then re-
generated for the final CSR to include all data through Day 202. 
 
 
Figures with similar format: 
Figure 7: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/H5N8 
by Study Day, Treatment Arm and Age Stratum, Per Protocol Population* 
Figure 8: 
Geometric Mean Titers of Neutralizing Antibody against A/H5N8 Study Day, 
Treatment Arm and Age Stratum, Modified Intent to Treat Population* 
Figure 9: 
Geometric Mean Titers of Neutralizing Antibody against A/H5N8 by Study Day, 
Treatment Arm and Age Stratum, Per Protocol Population* 
 


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Figure 10: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Modified 
Intent-to-Treat Population* 
[Implementation Note: A generic sample figure is shown below. The scatter plots should be presented 
in a single figure with separate panels for each visit (Baseline, D8, D22, D29, D43, D202. Visit labels 
should be included in the panel header. Within each panel distinct marker types and colors should be 
used to indicate the treatment arms, with treatment group labels included in a legend. ). Each treatment 
arm should have a unique color and marker shape, with open/closed markers used to distinguish strata 
within treatment arm (19-65, ≥65) The spearman correlation should be calculated over all subjects and 
annotated within each panel as “Spearman Correlation (r=0.xx, p=0.xx)”] 
 
Figure with Similar format: 
Figure 11: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population* 
 
 


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Figure 12: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population* 
[Implementation Note: A generic sample figure is shown below. The RCD curves should be presented 
in a single figure with separate panels for each study day (Baseline[Day1], Day 8, Day 22, Day 29, Day 
43, Day 202. Visit labels should be included in the panel headers. Within each panel individual curves 
should be used for each treatment arm and strata within treatment arm (ten curves). Each treatment arm 
should have a separate color with dashed/solid lines used to distinguish strata (19-65, ≥65)] 
[Implementation Note: repeat for all heterologous strains] 
 
 
Figure with Similar Format: 
Figure 13: 
Reverse Cumulative Distribution of Neutralizing Antibody against [Antigenically 
Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population 
 


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Figure 14: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population 
[Implementation Note: A generic sample figure is shown below. Planned Study Day is plotted along the 
x-axis, with visit labels as tick labels. Titer is plotted on the y-axis on the log-10 scale. GMT should be 
plotted at each visit with upper and lower error bars for the 95% CI for each treatment group with 
different marker shapes/colors for each treatment arm. Each treatment arm should have a separate color 
and marker shape, with open/closed markers and dashed/solid lines used to distinguish strata (19-65, 
≥65)] 
[Implementation Note: repeat for all heterologous strains] 
 
Figure with similar format: 
Figure 15: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population 
 


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Figure 16: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against [Antigenically Drifted Strain] by Study Day, Treatment Arm and Age 
Stratum, Per Protocol Population 
[Implementation Note: A generic sample figure is shown below. The scatter plots should be presented 
in a single figure with separate panels for each visit (Baseline, D8, D22, D29, D43, D202. Visit labels 
should be included in the panel header. Within each panel distinct marker types and colors should be 
used to indicate the treatment arms, with treatment group labels included in a legend. Each treatment 
arm should have a unique color and marker shape, with open/closed markers used to distinguish strata 
within treatment arm (19-65, ≥65) The spearman correlation should be calculated over all subjects and 
annotated within each panel as “Spearman Correlation (r=0.xx, p=0.xx)”] 
[Implementation Note: repeat for all heterologous strains] 
 
 
Figures with similar format (may repeat as needed for additional strains): 
Figure 17: 
Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
[Antigenically Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per 
Protocol Population 
Figure 18: 
Correlation of Neutralizing Antibody Against 2017 A/H7N9 and [Antigenically 
Drifted Strain] by Study Day, Treatment Arm and Age Stratum, Per Protocol 
Population 


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14.3.1 Safety Figures 
14.3.1.1 Solicited Adverse Events 
Figure 19: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Study 
Vaccination 
[Implementation Note: A Generic figure is shown below. A vertical bar chart should be presented in 3 
image files (overall and by strata) with separate panels for each treatment arm, age strata and study 
vaccination (5 rows (treatment arms) x 2 columns (vaccination #)). Axes should be labeled as follows: 
x-axis label: Study Day, y-axis label: Percentage of Subjects (%). The treatment arms should be 
indicated in the panel headers including “(N=X)”, where N = the number of subjects in the in the Safety 
Population who received the relevant dose. Subjects are counted at most once at the maximum severity 
across all systemic events reported for the specified time point] 
 
 
Figure with similar format: 
Figure 20: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Study Vaccination 
 


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14.3.1.2 Unsolicited Adverse Events 
Figure 21: 
Frequency of Unsolicited Adverse Events by MedDRA System Organ Class 
and Severity 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in 3 image files (overall and by 
strata) with separate panels for each treatment arm (5 columns (treatment arms)). Axes should be 
labeled as follows: y-axis label: System Organ Class, y-axis label: Number of Events. The treatment 
arms should be indicated in the panel headers including “(N=X)”, where N = the number of subjects in 
the in the Safety Population. The y-axis should present all SOCs reported by at least 1 subject and an 
“All Events” category. Y-axis should be sorted with “All Events first, then in decreasing order of total 
incidence] 
 
 


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Figure 22: 
Incidence of Unsolicited Adverse Events by MedDRA System Organ Class 
and Severity 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in 3 image files with separate panels 
for each treatment arm (5 columns). Axes should be labeled as follows: y-axis label: System Organ 
Class, x-axis label: Percentage of Subjects (%). The treatment arms should be indicated in the panel 
headers including “(N=X)”, where N = the number of subjects in the in the Safety Population. Subjects 
are counted at most once at the maximum severity across for any events in the applicable SOC. The y-
axis should present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis should 
be sorted with “All Events” first then in decreasing order of total incidence]  
 
 
 


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Figure 23: 
Frequency of Adverse Events by MedDRA System Organ Class and Relationship to 
Treatment 
[Implementation Note: A generic sample figure is shown below. This figure includes all unsolicited 
events across all vaccinations. A horizontal bar chart should be presented in 3 image files with separate 
panels for each treatment arm, age strata and study vaccination (5 columns (treatment arms). Axes 
should be labeled as follows: y-axis label: System Organ Class, y-axis label: Number of Events. The 
treatment arms should be indicated in the panel headers including “(N=X)”, where N = the number of 
subjects in the in the Safety Population. The y-axis should present all SOCs reported by at least 1 subject 
and an “All Events” category. Y-axis should be sorted with “All Events first  then in decreasing order 
of total frequency] 
 
 


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Figure 24: 
Incidence of Adverse Events by MedDRA System Organ Class and Relationship to 
Treatment 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in a 3 image files (overall and by 
strata)  with separate panels for each treatment arm (5 columns (treatment arms). Axes should be labeled 
as follows: y-axis label: System Organ Class, x-axis label: Percentage of Subjects (%). The treatment 
arms should be indicated in the panel headers including “(N=X)”, where N = the number of subjects in 
the in the Safety Population. Subjects are counted at most once at the maximum relationship (related 
>not-related) across for any events in the applicable SOC. The y-axis should present all SOCs reported 
by at least 1 subject and an “All Events” category. Y-axis should be sorted with “All Events first, then 
in decreasing order of total incidence across groups]  
 
 


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14.3.5 Displays of Laboratory Results 
Figure 25: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter and Treatment Arm – White Blood Cells 
[Implementation note: A generic figure is shown below. Plot should be generated with all treatment 
groups in a single image file with panels for each treatment arm and strata (5 rows (treatment arms) x 2 
columns (strata)) with a box plot shown for each post-baseline study day that labs are drawn (D8, D22, 
D29). Y-axis should be labeled “[Parameter] Change from baseline ([units]). Repeat for all clinical 
laboratory parameters: WBC, Hgb, PLT, ALT, T. Bili, Cr] 
 
Figures with similar format: 
Figure 26: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Arm – Hemoglobin 
Figure 27: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Platelets 
Figure 28: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Arm – Alanine Aminotransferase (ALT) 
 
 


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Figure 29: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Total Bilirubin 
Figure 30: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Arm – Creatinine 
 


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APPENDIX 3. LISTINGS MOCK-UPS 
 
 
LIST OF LISTINGS 
Listing 1: 
16.1.6 - Listing of Subjects Receiving Investigational Product .................................. 172 
Listing 2: 
16.2.1 - Early Terminations or Discontinued Subjects ............................................... 173 
Listing 3: 
16.2.2.1 - Subject-Specific Protocol Deviations ......................................................... 174 
Listing 4: 
16.2.2.2 - Non-Subject-Specific Protocol Deviations ................................................. 175 
Listing 5: 
16.2.3 - Subjects Excluded from Analysis Populations .............................................. 176 
Listing 6: 
16.2.4.1 - Demographics Data ..................................................................................... 177 
Listing 7: 
16.2.4.2 – Pre-Existing and Concurrent Medical Conditions ...................................... 178 
Listing 8: 
16.2.6 - Individual Immunogenicity Response Data ................................................... 180 
Listing 9:  
16.2.7.1 - Solicited Events – Systemic Symptoms ...................................................... 181 
Listing 10:  
16.2.7.2 - Solicited Events – Local Symptoms ........................................................... 182 
Listing 11: 
16.2.7.3 - Unsolicited Adverse Events ........................................................................ 183 
Listing 12: 
16.2.8.1 - Clinical Laboratory Results – Hematology ................................................. 184 
Listing 13: 
16.2.8.2 - Clinical Laboratory Results – Hematology ................................................. 185 
Listing 14: 
16.2.9.1 - Vital Signs ................................................................................................... 186 
Listing 15: 
16.2.9.2 - Physical Exam Findings .............................................................................. 187 
Listing 16: 
16.2.10 - Concomitant Medications ............................................................................ 188 
Listing 17: 
16.2.11.1 - Pregnancy Reports – Maternal Information .............................................. 189 
Listing 18: 
16.2.11.2 - Pregnancy Reports – Gravida and Para ..................................................... 190 
Listing 19: 
16.2.11.3 - Pregnancy Reports – Live Birth Outcomes ............................................... 190 
Listing 20: 
16.2.11.4 - Pregnancy Reports – Still Birth Outcomes ............................................... 190 
Listing 21: 
16.2.11.5 - Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion 
Outcomes..................................................................................................................... 191 
 
 


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16.1.6 Listing of Subjects Receiving Investigational Product 
Listing 1: 
16.1.6 - Listing of Subjects Receiving Investigational Product 
Subject ID 
Randomized  
Treatment Arm 
Age Stratum 
Product Received Study 
Vaccination 1 
Product Received Study 
Vaccination 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2: 
16.2.1 - Early Terminations or Discontinued Subjects 
[Implementation Note: Category will be either “Early Termination” or “Treatment Discontinuation.” In the “Reason” column, concatenate any 
“specify” fields, including AE number and DV number.] 
Subject ID 
Treatment Arm 
Age Stratum 
Category 
Reason for Early Termination or Treatment Discontinuation 
Study Day 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.2 Protocol Deviations 
Listing 3: 
16.2.2.1 - Subject-Specific Protocol Deviations 
[Implementation Note: In the “Deviation” column, concatenate any and all “specify” fields (including visit number, etc.). If “Reason for Deviation” 
is “Other,” concatenate “specify” field, separate by a colon, e.g., “Other: Subject refusal.”] 
Subject 
ID 
Treatmen
t 
Group 
Age 
Stratum 
DV 
Number 
Deviatio
n 
Deviati
on 
Catego
ry 
Study 
Day 
Reason 
for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Resolution 
Commen
ts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 4: 
16.2.2.2 - Non-Subject-Specific Protocol Deviations 
[Implementation Note: In the “Deviation” column, concatenate any and all “specify” fields (including visit number, etc.). If “Reason for Deviation” 
is “Other,” concatenate “specify” field, separate by a colon, e.g., “Other: Subject refusal.”] 
Site 
Deviation 
Start 
Date 
End Date 
Reason for 
Deviation 
Deviation 
Resulted in 
Subject 
Termination
? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.


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16.2.3 Subjects Excluded from the Analysis 
Listing 5: 
16.2.3 - Subjects Excluded from Analysis Populations 
[Implementation Note: This data in this listing should be congruent with the “Analysis Populations by Treatment Group” table. The reasons included 
here should match the SAP text that describes who will be excluded from analyses.] 
Treatment Group 
Age Stratum 
Subject ID 
Analyses in which 
Subject is Included 
Analyses from which  
Subject is Excluded 
Results Available? 
Reason Subject 
Excluded 
 
 
 
[e.g., Safety, ITT, PP] 
[e.g., Safety, ITT, PP, Day x] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: “Yes” in the “Results available” column indicates that available data were removed from the analysis. “No” indicates that no data were available for inclusion in the analysis. 
 


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16.2.4 Demographic Data 
Listing 6: 
16.2.4.1 - Demographics Data 
[Implementation Note: If a subject is multi-racial, in “Race” column, note “Multiple: (list races, separated by a comma).”] 
Subject ID 
Treatment Group 
Age Stratum 
Sex 
Age at Enrollment 
(years) 
Ethnicity 
Race 
BMI 
Seasonal 
Influenza 
Received 
(2016-2017) 
Seasonal 
Influenza 
Received 
(2017-2018) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 7: 
16.2.4.2 – Pre-Existing and Concurrent Medical Conditions 
[Implementation Note: “Condition Start Day” and “Condition End Day” are relative to enrollment (which is Day 1, day before enrollment is Day -
1). If ongoing, display “Ongoing” in the “Condition End Day” column 
 
Subject 
ID 
Treatment 
Group 
Age 
Stratum 
MH 
Number 
Medical History 
Term 
Condition Start 
Day  
Condition End 
Day 
MedDRA System Organ 
Class 
MedDRA Preferred 
Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.5 Compliance and/or Drug Concentration Data (if available) 
Not applicable for this study. 
 


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16.2.6 Individual Immunogenicity Response Data 
Listing 8: 
16.2.6 - Individual Immunogenicity Response Data 
Subject 
ID 
Treatment 
Group 
Age Stratum 
Planned Time Point 
Actual Study 
Day 
Assay 
Strain 
Titer Replicate 
1 
Titer Replicate 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.7 Adverse Events 
Listing 9:  16.2.7.1 - Solicited Events – Systemic Symptoms 
Subject ID 
Treatment Arm 
Age Stratum 
Vac Number 
Post Vac Day 
Assessmenta 
Symptom 
Severity 
Attributed to 
Alternate 
Etiology?b 
Alternate 
Etiology 
 
 
 
 
 
MA 
 
 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
b Grade 3 events only. 
 


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Listing 10:  16.2.7.2 - Solicited Events – Local Symptoms 
Subject ID 
Treatment Arm 
Age Stratum 
Vac Number 
Post Vac Day 
Assessmenta 
Symptom 
Severity 
 
 
 
 
 
MA 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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Listing 11: 16.2.7.3 - Unsolicited Adverse Events 
 
Adverse 
Event 
Associated 
with Vac # 
# of Days 
Post 
Associated 
Vac 
(Duration) 
Severity 
SAE? 
MAAE? 
PIMMC? 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken 
with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
 
SAE: No 
MAAE: Yes 
PIMMC: No 
 
 
 
 
 
 
 
Comments: 
Subject ID: , Treatment Arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Section 14.3.3 


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16.2.8 Individual Laboratory Measurements 
Listing 12: 16.2.8.1 - Clinical Laboratory Results – Hematology 
[Implementation Note: These listings (for hematology and chemistry) include all laboratory results, scheduled and unscheduled. These listings are 
not color-coded, but the severity should be included in parentheses after the result for abnormal results, e.g., 16.2 (Mild). The “extra” fields that are 
completed for abnormal results are not included in this listing; they are included in the listing of abnormal laboratory results that is included in the 
table shells.] 
Subject ID 
Treatment Arm 
Age 
Stratum 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Alanine 
aminotransferase  
(IU/L) 
Total Bilirubin 
(mg/dL) 
Creatinine 
(mg/dL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 13: 16.2.8.2 - Clinical Laboratory Results – Hematology 
Subject ID 
Treatment Arm 
Age 
Stratum 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
White Blood Cell 
(103/µL) 
Hemoglobin 
(g/dL) 
Platelets 
(103/µL)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 14: 16.2.9.1 - Vital Signs 
[Implementation Note: This listing includes all vital sign assessments, scheduled and unscheduled. These listings are not color-coded, but the severity 
should be included in parentheses after the result for abnormal assessments, e.g., 100.7 (Mild).] 
Subject ID 
Treatment Arm  
Age Stratum 
Planned 
Time Point 
Actual 
Study Day 
Temperature 
(°C) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Pulse 
(beats/min) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 15: 16.2.9.2 - Physical Exam Findings 
[Implementation Note: This listing includes all physical exam findings, scheduled and unscheduled. If a subject does not have any findings upon 
examination, they will not be included in this listing. If reported as an AE, display “Yes” with the AE Number in parentheses, e.g., “Yes (7)”.] 
Subject ID 
Treatment Arm 
Age 
Stratum 
Planned 
Time 
Point 
Actual 
Study Day 
Body System 
Abnormal Finding 
Reported as an AE? 
(AE Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.10 
Concomitant Medications 
Listing 16: 16.2.10 - Concomitant Medications 
[Implementation Note: “Medication Start Day” and “Medication End Day” are relative to enrollment (which is Day 1, day before enrollment is Day 
-1). For medication start dates that are > 30 days prior to enrollment, rather than use exact study days, categorize as follows: 
• 
> 5 years prior to enrollment 
• 
1-5 years prior to enrollment 
• 
1-12 months prior to enrollment 
If ongoing, display “Ongoing” in the “Medication End Day” column. If taken for an AE or MH, display “Yes” with the AE or MH Number in 
parentheses, e.g., “Yes (7)”.] 
Subject 
ID 
Treatment 
Group 
Age 
Stratum 
CM 
Number 
Medication 
Medication Start 
Day 
Medication End 
Day 
Indication 
Taken for an 
AE? 
(AE Number) 
Taken for a 
condition on Medical 
History? 
(MH Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.11 
Pregnancy Reports 
[Implementation Note: Only include the “Pregnancy Number” column if a subject has more than 1 pregnancy. Date of Conception will be calculated 
based on estimated delivery date. BMI will be calculated based on pre-pregnancy height and weight. Mother’s weight gain will be calculated based 
on pre-pregnancy weight and end of pregnancy weight. If a major congenital anomaly with previous pregnancy, display “Yes” and the text from the 
“specify” field, separated by a colon. If any substance use is reported, include a listing of substance use. If autopsy revealed an alternate etiology, 
display “Yes” and the text from the “specify” field, separated by a colon. If abnormality in product of conception, display “Yes” and the text from 
the “specify” field, separated by a colon.] 
Listing 17: 16.2.11.1 - Pregnancy Reports – Maternal Information 
 
Subject ID 
Treatment 
Arm 
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications 
Listing. 
 


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Listing 18: 16.2.11.2 - Pregnancy Reports – Gravida and Para 
 
 
 
Live Births 
 
 
 
 
 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PB1 
Very 
Early 
PB1 
Early 
PB1 
Late 
PB1 
Early 
TB2 
Full 
TB2 
Late 
TB2 
Post 
TB2 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly with 
Previous 
Pregnancy? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Preterm Birth 
2 Term Birth 
Note: Gravida includes the current pregnancy, para events do not. 
 
Listing 19: 16.2.11.3 - Pregnancy Reports – Live Birth Outcomes 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 
1 
minute 
Apgar 
Score, 5 
minutes 
Cord 
pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month 
of Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital Anomalies are included in the Adverse Event listing.  
 
Listing 20: 16.2.11.4 - Pregnancy Reports – Still Birth Outcomes 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, 
Etiology for Still 
Birth Identified? 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 21: 16.2.11.5 - Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Subject 
ID 
Date of Initial 
Report 
Fetus Number 
Pregnancy 
Outcome (for this 
Fetus) 
Gestational Age at 
Termination 
Abnormality in Product of 
Conception? 
Reason for Therapeutic 
Abortion